Kinetic Modeling Assisted Analysis of Vitamin C-Mediated Copper Redox Transformations in Aqueous Solutions.

The kinetics of oxidation of micromolar concentrations of ascorbic acid (AA) catalyzed by Cu(II) in solutions representative of biological and environmental aqueous systems has been investigated in both the presence and absence of oxygen. The results reveal that the reaction between AA and Cu(II) is a relatively complex set of redox processes whereby Cu(II) initially oxidizes AA yielding the intermediate ascorbate radical (A•-) and Cu(I). The rate constant for this reaction was determined to have a lower limit of 2.2 × 104 M-1 s-1. Oxygen was found to play a critical role in mediating the Cu(II)/Cu(I) redox cycle and the oxidation reactions of AA and its oxidized forms. Among these processes, the oxidation of the ascorbate radical by molecular oxygen was identified to play a key role in the consumption of ascorbic acid, despite being a slow reaction. The rate constant for this reaction (A•-+O2→DHA+O2•-) was determined for the first time with a calculated value of 54 ± 8 M-1 s-1. The kinetic model developed satisfactorily describes the Cu/AA/O2 system over a range of conditions including different concentrations of NaCl (0.2 and 0.7 M) and pH (7.4 and 8.1). Appropriate adjustments to the rate constant for the reaction between Cu(I) and O2 were found to account for the influence of the chloride ions and pH on the kinetics of the process. Additionally, the presence of Cu(III) as the primary oxidant resulting from the interaction between Cu(I) and H2O2 in the Cu(II)/AA system was confirmed, along with the coexistence of HO•, possibly due to an equilibrium established between Cu(III) and HO•.

A case of traumatic uterine avulsion in pregnancy.

Complete uterine avulsion is an extremely rare complication of trauma sustained during pregnancy. We present the case of a 21-year-old nullipara at 16 weeks' gestation who was involved in a high-speed motor vehicle collision with subsequent fetal demise. Initially she was hemodynamically stable and demonstrated small amounts of intraabdominal free fluid, therefore multidisciplinary conservative measures were undertaken. However, as her condition worsened, she was taken for exploratory laparotomy, revealing complete gravid uterine avulsion at the level of the cervicoisthmic junction. Due to hemodynamic instability and concerns for retroperitoneal bleeding, a supracervical hysterectomy was performed. Although a rare occurrence, our case demonstrates the need for a high level of suspicion for uterine avulsion in certain cases of trauma in pregnancy. This highlights the false reassurance provided by stable vitals in a pregnant patient that may mask ongoing bleeding and development of hemorrhagic shock, the importance of interpreting different imaging modalities together when the cause of instability is unclear, and the utility of a multidisciplinary approach. While our patient underwent hysterectomy due to hemodynamic instability, it is unknown whether earlier investigation with laparoscopy to confirm uterine integrity may have circumvented this and allowed for fertility-sparing management. As such, our case encourages the utilization of early diagnostic laparoscopy if there is concern for uterine avulsion for the consideration of alternative surgical interventions for management.

Maintenance of methylation profile in imprinting control regions in human induced pluripotent stem cells.

BACKGROUND: Parental imprinting is an epigenetic mechanism that leads to monoallelic expression of a subset of genes depending on their parental origin. Imprinting disorders (IDs), caused by disturbances of imprinted genes, are a set of rare congenital diseases that mainly affect growth, metabolism and development. To date, there is no accurate model to study the physiopathology of IDs or test therapeutic strategies. Human induced pluripotent stem cells (iPSCs) are a promising cellular approach to model human diseases and complex genetic disorders. However, aberrant hypermethylation of imprinting control regions (ICRs) may appear during the reprogramming process and subsequent culture of iPSCs. Therefore, we tested various conditions of reprogramming and culture of iPSCs and performed an extensive analysis of methylation marks at the ICRs to develop a cellular model that can be used to study IDs. RESULTS: We assessed the methylation levels at seven imprinted loci in iPSCs before differentiation, at various passages of cell culture, and during chondrogenic differentiation. Abnormal methylation levels were found, with hypermethylation at 11p15 H19/IGF2:IG-DMR and 14q32 MEG3/DLK1:IG-DMR, independently of the reprogramming method and cells of origin. Hypermethylation at these two loci led to the loss of parental imprinting (LOI), with biallelic expression of the imprinted genes IGF2 and DLK1, respectively. The epiPS™ culture medium combined with culturing of the cells under hypoxic conditions prevented hypermethylation at H19/IGF2:IG-DMR (ICR1) and MEG3/DLK1:IG-DMR, as well as at other imprinted loci, while preserving the proliferation and pluripotency qualities of these iPSCs. CONCLUSIONS: An extensive and quantitative analysis of methylation levels of ICRs in iPSCs showed hypermethylation of certain ICRs in human iPSCs, especially paternally methylated ICRs, and subsequent LOI of certain imprinted genes. The epiPS™ culture medium and culturing of the cells under hypoxic conditions prevented hypermethylation of ICRs in iPSCs. We demonstrated that the reprogramming and culture in epiPS™ medium allow the generation of control iPSCs lines with a balanced methylation and ID patient iPSCs lines with unbalanced methylation. Human iPSCs are therefore a promising cellular model to study the physiopathology of IDs and test therapies in tissues of interest.

Discovery and fine mapping of Rph28: a new gene conferring resistance to Puccinia hordei from wild barley.

KEY MESSAGE: A new gene Rph28 conferring resistance to barley leaf rust was discovered and fine-mapped on chromosome 5H from wild barley. Leaf rust is a highly destructive disease of barley caused by the fungal pathogen Puccinia hordei. Genetic resistance is considered to be the most effective, economical and eco-friendly approach to minimize losses caused by this disease. A study was undertaken to characterize and fine map a seedling resistance gene identified in a Hordeum vulgare ssp. spontaneum-derived barley line, HEB-04-101, that is broadly effective against a diverse set of Australian P. hordei pathotypes. Genetic analysis of an F3 population derived from a cross between HEB-04-101 and the H. vulgare cultivar Flagship (seedling susceptible) confirmed the presence of a single dominant gene for resistance in HEB-04-101. Selective genotyping was performed on representative plants from non-segregating homozygous resistant and homozygous susceptible F3 families using the targeted genotyping-by-sequencing (tGBS) assay. Putatively linked SNP markers with complete fixation were identified on the long arm of chromosome 5H spanning a physical interval between 622 and 669 Mb based on the 2017 Morex barley reference genome assembly. Several CAPS (cleaved amplified polymorphic sequences) markers were designed from the pseudomolecule sequence of the Morex assembly (v1.0 and v2.0), and 16 polymorphic markers were able to delineate the RphHEB locus to a 0.05 cM genetic interval spanning 98.6 kb. Based on its effectiveness and wild origin, RphHEB is distinct from all other designated Rph genes located on chromosome 5H and therefore the new locus symbol Rph28 is recommended for RphHEB in accordance with the rules and cataloguing system of barley gene nomenclature.

Recycling waste plastics in roads: A life-cycle assessment study using primary data.

The present study investigates - from an environmental perspective - the processes that lead to the conversion of waste plastics into recycled plastic pellets to be used either as an additive (wet method) or as a replacement of natural aggregate (dry method) in the production of asphalt mixes. Data from recycling facilities in Victoria, Australia, were collected and used as the basis for a comparative life cycle assessment (LCA) study. Analyses were conducted by considering several replacement ratios of virgin material by its recycled counterpart in the so-called wet and dry method. A case study considering the production of recycled-plastic asphalt to be applied in the construction of a typical surface layer of a road in Victoria was evaluated. In general, the results show that recycling plastics as a polymer for bitumen modification and as a synthetic aggregate replacement in asphalt mixes has the potential to be environmentally advantageous compared to their virgin counterpart (i.e. virgin polymers and natural quarry aggregates).

Extending the window for thrombolysis for treatment of acute ischaemic stroke during pregnancy: a review.

Historically, safety of intravenous recombinant tissue plasminogen activator (IV rt-PA) for the treatment of acute ischaemic stroke (AIS) is limited to use within 4.5 hours from symptom onset. Recent studies suggest the treatment window may be extended when patients have salvageable brain tissue on advanced neuroimaging. This paper describes a novel use of IV rt-PA for treatment of AIS in a pregnant patient within an extended-time window (>4.5 hours, and <9 hours) based on advanced neuroimaging with a favourable outcome. TWEETABLE ABSTRACT: Novel use of IV rt-PA for treatment of AIS in pregnancy within an extended-time window based on advanced imaging with a favourable outcome.

A shift in abscisic acid/gibberellin balance underlies retention of dormancy induced by seed development temperature.

Through a combination of physiological, pharmacological, molecular and targeted metabolomics approaches, we showed that retention of wheat (Triticum aestivum L.) seed dormancy levels induced by low and high seed development temperatures during post-desiccation phases is associated with modulation of gibberellin (GA) level and seed responsiveness to abscisic acid (ABA) and GA via expression of TaABI5 and TaGAMYB, respectively. Dormancy retention during imbibition, however, is associated with modulations of both ABA level and responsiveness via expression of specific ABA metabolism (TaNCED2 and TaCYP707A1) and signalling (TaPYL2, TaSnRK2, TaABI3, TaABI4 and TaABI5) genes, and alterations of GA levels and responsiveness through expression of specific GA biosynthesis (TaGA20ox1, TaGA20ox2 and TaGA3ox2) and signalling (TaGID1 and TaGID2) genes, respectively. Expression patterns of GA signalling genes, TaRHT1 and TaGAMYB, lacked positive correlation with that of GA regulated genes and dormancy level observed in seeds developed at the two temperatures, implying their regulation at post-transcriptional level. Our results overall implicate that a shift in ABA/GA balance underlies retention of dormancy levels induced by seed development temperature during post-desiccation and imbibition phases. Consistently, genes regulated by ABA and GA during imbibition overlapped with those differentially expressed between imbibed seeds developed at the two temperatures and mediate different biological functions.

Effectiveness of the Iron Chelator CN128 in Mitigating the Formation of Dopamine Oxidation Products Associated with the Progression of Parkinson's Disease.

The occurrence and progression of Parkinson's disease (PD) has been associated with the observation of elevated iron concentrations in the substantia nigra pars compacta (SNpc). While the reasons for the impact of elevated iron concentrations remain unclear, one hypothesis is that the presence of labile iron induces the oxidation of dopamine (DA) to toxic quinones such as aminochrome (DAC) and reactive oxygen species (ROS). As such, one of the proposed therapeutic strategies has been the use of iron chelators such as deferiprone (DFP) (which is recognized to have limitations related to its rapid degradation in the liver) to reduce the concentration of labile iron. In this study, a detailed investigation regarding the novel iron chelator, CN128, was conducted and a kinetic model developed to elucidate the fundamental behavior of this chelator. The results in this work reveal that CN128 is effective in alleviating the toxicity induced by iron and DA to neurons when DA is present at moderate concentrations. When all the iron is chelated by CN128, the formation of DAC and the oxidation of DA can be reduced to levels identical to that in the absence of iron. The production of H2O2 is lower than that generated via the autoxidation of the same amount of DA. However, when severe leakage of DA occurs, the application of CN128 is insufficient to alleviate the associated toxicity. This is attibuted to the less important role of iron in the production of toxic intermediates at high concentrations of DA. CN128 is superior to DFP with regard to the reduction in formation of DAC and elevation in DA concentration. In summary, the results of this study suggest that prodromal application of the chelator CN128 could be effective in preventing the onset and slowing the early stage development of PD symptoms associated with oxidants and toxic intermediates resulting from the iron-mediated oxidation of the neurotransmitter dopamine with CN128 likely to be superior to DFP in view of its greater in vivo availability and less problematic side effects.

Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

Recent advances in Cu-Fenton systems for the treatment of industrial wastewaters: Role of Cu complexes and Cu composites.

Cu-based Fenton systems have been recognized as a promising suite of technologies for the treatment of industrial wastewaters due to their high catalytic oxidation capacity. Rapid progress regarding Cu Fenton systems has been made not only in fundamental mechanistic aspects of these systems but also with regard to applications over the past decade. Based on available literature, this review synthesizes the recent advances regarding both the understanding and applications of Cu-based Fenton processes for industrial wastewater treatment. Cu-based catalysts that are essential to the effectiveness of use of Cu Fenton reactions for oxidation of target species are mainly classified into two types: (i) Cu complexes with organic or inorganic ligands, and (ii) Cu composites with inorganic materials. Performance of the Cu-based catalysts for the removal of organic pollutants in industrial wastewaters are reviewed, with the key operating parameters illustrated. Furthermore, the roles of Cu complexes and composites in both homogeneous and heterogeneous Cu-Fenton systems are critically examined with particular focus on the mechanisms involved. Perspectives and future efforts needed for Cu-based Fenton systems using Cu complexes and composites for industrial wastewater treatment are presented.

Effect of Chloride and Suwannee River Fulvic Acid on Cu Speciation: Implications to Cu Redox Transformations in Simulated Natural Waters.

Copper is a critical trace nutrient and, at higher concentrations, a toxicant in natural waters, with the relative rates of transformation between the Cu(I) and Cu(II) oxidation states being key to its speciation, bioavailability, and toxicity. While the influence of chloride (Cl-) and natural organic matter on Cu speciation and associated redox transformations has been studied separately, their combined influence on Cu speciation and Cu redox transformations has not been examined. As such, in this study, we investigate the impact of Cl- and Suwannee River fulvic acid (SRFA) on Cu(II) reduction and Cu(I) oxidation kinetics at pH 8.2. SRFA plays a dual role in providing Cu(II) reducing moieties as well as Cu ligating sites. Our results indicate that the SRFA-bound Cu(II) is less reactive than the inorganic Cu(II), and the SRFA-bound Cu(I) being much more rapidly oxidized than the inorganic Cu(I). The presence of Cl- weakens Cu(II) binding by SRFA, thereby increasing the reactivity of Cu(II). Similarly, weakening of Cu(I) binding by SRFA and concomitant binding of Cu(I) by Cl- stabilizes Cu(I). Our results further show that continuous formation of hydrogen peroxide occurs in the presence of Cu(II), SRFA, and Cl- in air-saturated solution with the presence of H2O2 enhancing the dynamic nature of the system.

Integrated Flow-Electrode Capacitive Deionization and Microfiltration System for Continuous and Energy-Efficient Brackish Water Desalination.

Flow-electrode capacitive deionization (FCDI) is an emerging electrochemically driven technology for brackish and/or sea water desalination with merits of large salt adsorption capacity, high flow efficiency, and easy electrode management. While FCDI holds promise for continuous operation, there are very few investigations with regard to the regeneration/reuse of flowable electrodes and the separation of brine from electrodes with these operation prerequisites for real nonintermittent water desalination. In this study, we propose a novel module design to achieve these critical steps involving integration of an FCDI cell and a ceramic microfiltration (MF) contactor. Our investigations reveal that the brine discharge rate is the dominant factor for stable and efficient operation of the integrated module. Results obtained show that the integrated FCDI/MF system can be used to successfully separate brackish water (of salinities 1, 2 and 5 g L-1) into both a potable stream (<0.5 g L-1) and a brine stream (concentrated by 2-20 times) in a continuous manner with extremely high water recovery rates (up to 97%) and reasonable energy consumption. Another notable characteristic of the integrated system is the high thermodynamic energy efficiency (∼30%) with such efficiencies 4-5 times larger than those of conventional capacitive deionization units and comparable to reverse osmosis and electrodialysis systems achieving similar separation efficiencies. In brief, the results of studies described here indicate that continuous and efficient operation of FCDI is a real possibility and pave the way for scale-up of this emerging technology.

Amalgam Strength Resistance to Various Contaminants.

PURPOSE:: The purpose of this study was to quantify the relative strength tolerance of 1-day and 30-day amalgam following saturation contamination with water, saliva, blood, and handpiece lubricant oil during condensation. METHODS AND MATERIALS:: Valiant PhD XT amalgam was tested with 300 shear-strength (N=15) and 120 compressive-strength (N=6) specimens, divided into 1-day and 30-day groups, each with control, water, saliva, blood, and lubricant oil contamination samples. Shear specimens were condensed in 4 × 4-mm anchor wells inundated with contaminant fluids before adding a ring mold with 3.5-mm-diameter central hole adapted immediately to the top for continued condensation under contaminant-submerged conditions. Compressive specimen samples were condensed while completely inundated by each contaminant using the American Dental Association Specification No. 1 amalgam mold apparatus. All specimens were tested with the Instron E3000 and E10000 at 0.5 mm/min, with data statistically evaluated using the Kruskal-Wallis procedure with IBM SPSS v25 and Wilcoxon signed ranks test. RESULTS:: Shear test values (mean±SD) following intracapsular and extracapsular contamination after 30 days under 100% humidity at 37°C were as follows: control, 30.97±5.41 MPa; water, 30.63 ±4.41 MPa; saliva, 27.54 ±4.56 MPa; blood, 24.92 ±3.48 MPa; lubricant oil, 26.06 ±4.06 MPa. Compressive strengths (±SD) of similarly contaminated samples were as follows: control, 447.7 ±76.3 MPa; water, 343.6 ±70.1 MPa; saliva, 307.7 ±24.0 MPa; blood, 281.6 ±35.2 MPa; lubricant oil, 227.8 ±16.9 MPa. CONCLUSIONS:: Saliva, blood, and handpiece oil diminish compressive strength significantly, but water shows no statistically significant effect ( p>0.05). Amalgam 30-day shear strength is significantly altered by contamination with water, blood, or handpiece lubricant oil ( p<0.05). Remaining amalgam strength after extensive contamination may still be clinically functional relative to a previous ADA recommendation and when compared with resin-based direct restorative materials.

Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease.

Parkinson's disease is the second most common neurodegenerative disease. While age is the most significant risk factor, the exact cause of this disease and the most effective approaches to mitigation remain unclear. It has long been proposed that dopamine may play a role in the pathology of Parkinson's disease in view of its ability to generate both protein-modifying quinones such as aminochrome and reactive oxygen species, especially in the presence of pathological iron accumulation in the primary site of neuron loss. Given the clinically measured acidosis of post-mortem Parkinson's disease brain tissue, the interaction between dopamine and iron was investigated over a pH range of 7.4 to 6.5 with emphasis on the accumulation of toxic quinones and generation of reactive oxygen species. Our results show that the presence of iron accelerates the formation of aminochrome with ferrous iron (Fe[II]) being more efficient in this regard than ferric iron (Fe[III]). Our results further suggest that a reduced aminochrome rearrangement rate coupled with an enhanced turnover rate of Fe[II] as a result of brain tissue acidosis could result in aminochrome accumulation within cells. Additionally, under these conditions, the enhanced redox cycling of iron in the presence of dopamine aggravates oxidative stress as a result of the production of damaging reactive species, including hydroxyl radicals.

Liquid crystal polymer receiver modules for electron cyclotron emission imaging on the DIII-D tokamak.

A new generation of millimeter-wave heterodyne imaging receiver arrays has been developed and demonstrated on the DIII-D electron cyclotron emission imaging (ECEI) system. Improved circuit integration, improved noise performance, and enhanced shielding from out-of-band emission are made possible by using advanced liquid crystal polymer (LCP) substrates and monolithic microwave integrated circuit (MMIC) receiver chips. This array exhibits ∼15 dB additional gain and >30× reduction in noise temperature compared to previous generation ECEI arrays. Each LCP horn-waveguide module houses a 3 × 3 mm GaAs MMIC receiver chip, which consists of a low noise millimeter-wave preamplifier, balanced mixer, and IF amplifier together with a local oscillator multiplier chain driven at ∼12 GHz. A proof-of-principle partial LCP instrument with 5 poloidal channels was installed on DIII-D in 2017, with a full proof-of-principle system (20 poloidal × 8 radial channels) installed and commissioned in early 2018. The enhanced shielding of the LCP modules is seen to greatly reduce the sensitivity of ECEI signals to out-of-band microwave noise which has plagued previous ECEI studies on DIII-D. The LCP ECEI system is expected to be a valuable diagnostic tool for pedestal region measurements, focusing particularly on electron temperature evolution during edge localized mode bursting.

Millimeter-wave system-on-chip advancement for fusion plasma diagnostics.

Recent advances in radio-frequency system-on-chip technology have provided mm-wave fusion plasma diagnostics with the capability to overcome major challenges such as space inefficiency, inflexible installation, sensitivity, susceptibility to EMI, and prohibitively high cost of conventional discrete component assemblies as higher imaging resolution and data accuracy are achieved by increasing the number of channels. Nowadays, shrinking transistor gate lengths on fabrication techniques have enabled hundreds of GHz operation, which is suitable for millimeter-wave diagnostics on current and future tokamaks. The Davis Millimeter Wave Research Center (DMRC) has successfully developed V-band (55-75 GHz) transmitter and receiver chips for Microwave Imaging Reflectometer (MIR) instruments. The transmitter can illuminate 8 different frequencies simultaneously within 55-75 GHz. Moreover, the receiver has the capability to amplify the reflected signal (>30 dB) while offering 10-30× reduction in noise temperature compared to current MIR instruments. Plasma diagnostics requires ultra-wideband (more than 20 GHz) operation which is approximately nine times wider bandwidth than the recent commercial impetus for communication systems. Current efforts are underway for gallium-arsenide monolithic microwave integrated circuit receiver chips at W-band (75-110 GHz) and F-band (90-140 GHz) permitting measurements at higher toroidal magnetic fields.

Oxidant Generation Resulting from the Interaction of Copper with Menadione (Vitamin K3)-a Model for Metal-mediated Oxidant Generation in Living Systems.

The oxidation of hydroquinones is of interest both due to the generation of reactive oxygen species (ROS) and to the implications to trace metal redox state. Menadione (MNQ), a typical toxicant quinone used extensively for studying the mechanisms underlying oxidative stress, is known to be an effective source of exogenous ROS. In this study, the kinetics and mechanism of the oxidation of menadiol (MNH2Q, the reduced form of MNQ) in the absence and presence of copper (Cu) over the pH range 6.0-7.5 was examined. The autoxidation rate increased with increasing pH and concentration of O2 and also slightly increased with increasing concentration of MNH2Q and MNQ with Cu shown to play a significant role in catalysing the oxidation of MNH2Q. A kinetic model showed that the mono-deprotonated menadiol, MNHQ-, accounted for the pH dependence of the autoxidation rate. In this proposed mechanism, both MNH2Q and MNHQ- species were oxidized quickly by Cu(II), generating menadione semiquinone (MNSQ•-) and superoxide (O2•-) and the reduced form of Cu, Cu(I). Oxygen not only facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) but also effectively removed MSNQ•-, generating the important chain-propagating species O2•-. The model demonstrated that Cu(I) was a significant sink of O2•- resulting in the generation of H2O2 with subsequent generation of highly oxidative intermediates including Cu(III). These results provide considerable insight into the clinical significance of the biological activation and detoxification of MNQ with the kinetic model developed of use in identifying key processes in the generation of harmful oxidants in living systems.