Installing Quinol Proton/Electron Mediators onto Non-Heme Iron Complexes Enables Them to Electrocatalytically Reduce O2 to H2O at High Rates and Low Overpotentials.

We prepare iron(II) and iron(III) complexes with polydentate ligands that contain quinols, which can act as electron proton transfer mediators. Although the iron(II) complex with N-(2,5-dihydroxybenzyl)-N,N',N'-tris(2-pyridinylmethyl)-1,2-ethanediamine (H2qp1) is inactive as an electrocatalyst, iron complexes with N,N'-bis(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H4qp2) and N-(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H2qp3) were found to be much more active and more selective for water production than a previously reported cobalt-H2qp1 electrocatalyst while operating at low overpotentials. The catalysts with H2qp3 can enter the catalytic cycle as either Fe(II) or Fe(III) species; entering the cycle through Fe(III) lowers the effective overpotential. On the basis of their TOF0 values, the successful iron-quinol complexes are better electrocatalysts for oxygen reduction than previously reported iron-porphyrin compounds, with the Fe(III)-H2qp3 arguably being the best homogeneous electrocatalyst for this reaction. With iron, the quinol-for-phenol substitution shifts the product selectivity from H2O2 to water with little impact on the overpotential, but unlike cobalt, this substitution also greatly improves the activity, as assessed by TOFmax, by hastening the protonation and oxygen binding steps. The addition of a second quinol further enhances the activity and selectivity for water but modestly increases the effective overpotential.

Simulation-based training for intraoperative posterior capsule rupture management: an analysis of nontechnical skills development and the relationship between technical and nontechnical skills.

OBJECTIVES: To analyse development of individual nontechnical skills (NTS) domains after undertaking a previously developed simulation-based training model and analyse the relationship between technical skills (TS) and NTS in ophthalmic surgery. METHODS: The simulation-based training model involved a cataract surgery case complicated by intraoperative posterior capsule rupture. Cataract surgeons underwent the simulation twice, separated by a training intervention. Two blinded independent experts assessed participants' NTS using HUFOES, NOn-Technical Skills for Surgeons (NOTSS), and the OSATS global rating scale for TS. Paired t-tests assessed differences in individual NTS domains, with p < 0.05 indicating significance. The Pearson Product Moment Correlation Coefficient was used to assess the correlation between scores from each scoring system. RESULTS: All NTS domains within HUFOES and NOTSS demonstrated statistically significant improvements secondary to the training intervention. Positive correlations were demonstrated between HUFOES and OSATS scores in the pre- and post-training simulations, r = 0.870 (p < 0.001) and r = 0.861 (p < 0.001), respectively. Positive correlations were also demonstrated between NOTSS and OSATS scores in pre- and post-training simulations, r = 0.849 (p < 0.001) and r = 0.757 (p = 0.001), respectively. Positive correlations were demonstrated between HUFOES and NOTSS scores; r = 0.979 (p < 0.001) (n = 17) and r = 0.959 (p < 0.001) for pre- and post-training simulations, respectively. CONCLUSION: All NTS domains contained within HUFOES and NOTSS demonstrated significant increases following the completion of the simulation-based training model. Positive correlations exist between an ophthalmic surgeon's TS and NTS. This is the first study to report these findings within ophthalmic surgery.

Diquinol Functionality Boosts the Superoxide Dismutase Mimicry of a Zn(II) Complex with a Redox-Active Ligand while Maintaining Catalyst Stability and Enhanced Activity in Phosphate Solution.

In the current work, we demonstrate ligand design concepts that significantly improve the superoxide dismutase (SOD) activity of a zinc complex; the catalysis is enhanced when two quinol groups are present in the polydentate ligand. We investigate the mechanism through which the quinols influence the catalysis and determine the impact of entirely removing a chelating group from the original hexadentate ligand. Our results suggest that SOD mimicry with these compounds requires a ligand that coordinates Zn(II) strongly in both its oxidized and reduced forms and that the activity proceeds through Zn(II)-semiquinone complexes. The complex with two quinols displays greatly enhanced catalytic ability, with the activity improving by as much as 450% over a related complex with a single quinol. In the reduced form of the diquinol complex, one quinol appears to coordinate to the zinc much more weakly than the other. We believe that superoxide can more readily displace this portion of the ligand, facilitating its coordination to the metal center and thereby hastening the SOD reactivity. Despite the presence of two redox-active groups that may communicate through intramolecular hydrogen bonding and redox tautomerism, only one quinol undergoes two-electron oxidation to a para-quinone during the catalysis. After the formation of the para-quinone, the remaining quinol deprotonates and binds tightly to the metal, ensuring that the complex remains intact in its oxidized state, thereby maintaining its catalytic ability. The Zn(II) complex with the diquinol ligand is highly unusual for a SOD mimic in that it performs more efficiently in phosphate solution.

Proton MR Spectroscopy of Pediatric Brain Disorders.

In vivo MR spectroscopy is a non -invasive methodology that provides information about the biochemistry of tissues. It is available as a "push-button" application on state-of-the-art clinical MR scanners. MR spectroscopy has been used to study various brain diseases including tumors, stroke, trauma, degenerative disorders, epilepsy/seizures, inborn errors, neuropsychiatric disorders, and others. The purpose of this review is to provide an overview of MR spectroscopy findings in the pediatric population and its clinical use.

A Macrocyclic Ligand Framework That Improves Both the Stability and T1-Weighted MRI Response of Quinol-Containing H2O2 Sensors.

Previously prepared Mn(II)- and quinol-containing magnetic resonance imaging (MRI) contrast agent sensors for H2O2 relied on linear polydentate ligands to keep the redox-activatable quinols in close proximity to the manganese. Although these provide positive T1-weighted relaxivity responses to H2O2 that result from oxidation of the quinol groups to p-quinones, these reactions weaken the binding affinity of the ligands, promoting dissociation of Mn(II) from the contrast agent in aqueous solution. Here, we report a new ligand, 1,8-bis(2,5-dihydroxybenzyl)-1,4,8,11-tetraazacyclotetradecane, that consists of two quinols covalently tethered to a cyclam macrocycle. The macrocycle provides stronger thermodynamic and kinetic barriers for metal-ion dissociation in both the reduced and oxidized forms of the ligand. The Mn(II) complex reacts with H2O2 to produce a more highly aquated Mn(II) species that exhibits a 130% greater r1, quadrupling the percentile response of our next best sensor. With a large excess of H2O2, there is a noticeable induction period before quinol oxidation and r1 enhancement occurs. Further investigation reveals that, under such conditions, catalase activity initially outcompetes ligand oxidation, with the latter occurring only after most of the H2O2 has been depleted.

Algorithms for segmenting cerebral time-of-flight magnetic resonance angiograms from volunteers and anemic patients.

Purpose: To evaluate six cerebral arterial segmentation algorithms in a set of patients with a wide range of hemodynamic characteristics to determine real-world performance. Approach: Time-of-flight magnetic resonance angiograms were acquired from 33 subjects: normal controls ( N = 11 ), sickle cell disease ( N = 11 ), and non-sickle anemia ( N = 11 ) using a 3 Tesla Philips Achieva scanner. Six segmentation algorithms were tested: (1) Otsu's method, (2) K-means, (3) region growing, (4) active contours, (5) minimum cost path, and (6) U-net machine learning. Segmentation algorithms were tested with two region-selection methods: global, which selects the entire volume; and local, which iteratively tracks the arteries. Five slices were manually segmented from each patient by two readers. Agreement between manual and automatic segmentation was measured using Matthew's correlation coefficient (MCC). Results: Median algorithm segmentation times ranged from 0.1 to 172.9 s for a single angiogram versus 10 h for manual segmentation. Algorithms had inferior performance to inter-observer vessel-based ( p < 0.0001 , MCC = 0.65 ) and voxel-based ( p < 0.0001 , MCC = 0.73 ) measurements. There were significant differences between algorithms ( p < 0.0001 ) and between patients ( p < 0.0042 ). Post-hoc analyses indicated (1) local minimum cost path performed best with vessel-based ( p = 0.0261 , MCC = 0.50 ) and voxel-based ( p = 0.0131 , MCC = 0.66 ) analyses; and (2) higher vessel-based performance in non-sickle anemia ( p = 0.0002 ) and lower voxel-based performance in sickle cell ( p = 0.0422 ) compared with normal controls. All reported MCCs are medians. Conclusions: The best-performing algorithm (local minimum cost path, voxel-based) had 9.59% worse performance than inter-observer agreement but was 3 orders of magnitude faster. Automatic segmentation was non-inferior in patients with sickle cell disease and superior in non-sickle anemia.

Illuminating subduction zone rheological properties in the wake of a giant earthquake.

Deformation associated with plate convergence at subduction zones is accommodated by a complex system involving fault slip and viscoelastic flow. These processes have proven difficult to disentangle. The 2010 M w 8.8 Maule earthquake occurred close to the Chilean coast within a dense network of continuously recording Global Positioning System stations, which provide a comprehensive history of surface strain. We use these data to assemble a detailed picture of a structurally controlled megathrust fault frictional patchwork and the three-dimensional rheological and time-dependent viscosity structure of the lower crust and upper mantle, all of which control the relative importance of afterslip and viscoelastic relaxation during postseismic deformation. These results enhance our understanding of subduction dynamics including the interplay of localized and distributed deformation during the subduction zone earthquake cycle.

Mechanistic substrates of a life history transition in male prairie voles: Developmental plasticity in affiliation and aggression corresponds to nonapeptide neuronal function.

Although prairie vole (Microtus ochrogaster) social behavior is well-characterized in adults, surprisingly little is known about the development of social behavior in voles. Further, the overwhelming majority of studies in prairie voles examine social behavior in a reproductive context. Here, we examine developmental plasticity in affiliation and aggression and their underlying neural correlates. Using sexually naïve males, we characterized interactions with an age-matched, novel, same-sex conspecific in four different age groups that span pre-weaning to adulthood. We found that prosocial behavior decreased and aggression increased as males matured. Additionally, pre-weaning males were more prosocial than nonsocial, whereas post-weaning males were more nonsocial than prosocial. We also examined nonapeptide neural activity in response to a novel conspecific in brain regions important for promoting sociality and aggression using the immediate early gene cFos. Assessment of developmental changes in neural activity showed that vasopressin neurons in the medial bed nucleus of the stria terminalis exhibit functional plasticity, providing a potential functional mechanism that contributes to this change in sociality as prairie voles mature. This behavioral shift corresponds to the transition from a period of allopatric cohabitation with siblings to a period of time when voles disperse and presumably attempt to establish and defend territories. Taken together our data provide a putative mechanism by which brain and behavior prepare for the opportunity to pairbond (characterized by selective affiliation with a partner and aggression toward unfamiliar conspecifics) by undergoing changes away from general affiliation and toward selective aggression, accounting for this important life history event.

Oxytocin Neurons Exhibit Extensive Functional Plasticity Due To Offspring Age in Mothers and Fathers.

The needs of offspring change as they develop. Thus, parents should concomitantly change their investment based on the age-related needs of the offspring as they mature. Due to the high costs of parental care, it is optimal for parents to exhibit a shift from intense caregiving of young offspring to promoting independence in older offspring. Yet, the neural mechanisms that underlie shifts in parental behavior are poorly understood, and little is known about how the parental brain responds to offspring of different ages. To elucidate mechanisms that relate to shifts in parental behavior as offspring develop, we examined behavioral and neural responses of male and female prairie voles (Microtus ochrogaster), a biparental rodent, to interactions with offspring at different stages of development (ranging from neonatal to weaning age). Importantly, in biparental species, males and females may adjust their behavior differentially as offspring develop. Because the nonapeptides, vasopressin (VP) and oxytocin (OT), are well known for modulating aspects of parental care, we focused on functional activity of distinct VP and OT cell groups within the maternal and paternal brain in response to separation from, reunion (after a brief period of separation) with, or no separation from offspring of different ages. We found several differences in the neural responses of individual VP and OT cell groups that varied based on the age of pups and sex of the parent. Hypothalamic VP neurons exhibit similar functional responses in both mothers and fathers. However, hypothalamic and amygdalar OT neurons exhibit differential functional responses to being separated from pups based on the sex of the parent. Our results also reveal that the developmental stage of offspring significantly impacts neural function within OT, but not VP, cell groups of both mothers and fathers. These findings provide insight into the functional plastic capabilities of the nonapeptide system, specifically in relation to parental behavior. Identifying neural mechanisms that exhibit functional plasticity can elucidate one way in which animals are able to shift behavior on relatively short timescales in order to exhibit the most context-appropriate and adaptive behaviors.

Inverse-collimated proton radiography for imaging thin materials.

Relativistic, magnetically focused proton radiography was invented at Los Alamos National Laboratory using the 800 MeV LANSCE beam and is inherently well-suited to imaging dense objects, at areal densities >20 g cm-2. However, if the unscattered portion of the transmitted beam is removed at the Fourier plane through inverse-collimation, this system becomes highly sensitive to very thin media, of areal densities <100 mg cm-2. Here, this inverse-collimation scheme is described in detail and demonstrated by imaging Xe gas with a shockwave generated by an aluminum plate compressing the gas at Mach 8.8. With a 5-mrad inverse collimator, an areal density change of just 49 mg cm-2 across the shock front is discernible with a contrast-to-noise ratio of 3. Geant4 modeling of idealized and realistic proton transports can guide the design of inverse-collimators optimized for specific experimental conditions and show that this technique performs better for thin targets with reduced incident proton beam emittance. This work increases the range of areal densities to which the system is sensitive to span from ∼25 mg cm-2 to 100 g cm-2, exceeding three orders of magnitude. This enables the simultaneous imaging of a dense system as well as thin jets and ejecta material that are otherwise difficult to characterize with high-energy proton radiography.