The Role of Electrode Catalyst Interactions in Enabling Efficient CO2 Reduction with Mo(bpy)(CO)(4) As Revealed by Vibrational Sum-Frequency Generation Spectroscopy

Group 6 metal carbonyl complexes ([M(bpy)(CO)4], M = Cr, Mo, W) are potentially promising CO2 reduction electrocatalysts. However, catalytic activity onsets at prohibitively negative potentials and is highly dependent on the nature of the working electrode. Here we report in situ vibrational SFG (VSFG) measurements of the electrocatalyst [Mo(bpy)(CO)4] at platinum and gold electrodes. The greatly improved onset potential for electrocatalytic CO2 reduction at gold electrodes is due to the formation of the catalytically active species [Mo(bpy)(CO)3]2– via a second pathway at more positive potentials, likely avoiding the need for the generation of [Mo(bpy)(CO)4]2–. VSFG studies demonstrate that the strength of the interaction between initially generated [Mo(bpy)(CO)4]•– and the electrode is critical in enabling the formation of the active catalyst via the low energy pathway. By careful control of electrode material, solvent and electrolyte salt, it should therefore be possible to attain levels of activity with group 6 complexes equivalent to their much more widely studied group 7 analogues

Roles for KCC transporters in the maintenance of lens transparency

PURPOSE. To determine whether the potassium chloride cotransporter (KCC) family is expressed in the rat lens and to ascertain whether the transporters are involved in the regulation of lens volume and transparency. METHODS. RT-PCR was performed on RNA extracted from fiber cells to identify members of the KCC family expressed in the lens. Western blot analysis and immunocytochemistry, using KCC isoform-specific antibodies, were used to verify expression at the protein level and to localize KCC isoform expression. Organ-cultured rat lenses were incubated in isotonic artificial aqueous humor (AAH) that contained either the KCCspecific inhibitor [(dihydronindenyl)oxy] alkanoic acid (DIOA), the KCC activator N-ethylmaleimide (NEM), or the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) for up to 18 hours. Lens wet weight was monitored, and lens transparency and tissue morphology were recorded with dark-field and confocal microscopy, respectively. RESULTS. Molecular experiments to characterize KCC isoform expression showed that KCC1, -3, and -4 were all expressed in the lens at both the transcript and protein levels and that KCC2 was not. Immunocytochemistry indicated that the three KCC isoforms exhibited distinct differentiation-dependent expression patterns, with KCC1 and -3 being restricted to the lens cortex, whereas KCC4 was found throughout the entire lens, including the lens core. In the lens cortex, most of the labeling for all KCC isoforms was cytoplasmic, whereas in the lens core, KCC4 labeling was associated with the membrane. Incubation of lenses in 100 M DIOA for 18 hours caused lenses to increase their wet weight and induced a cortical opacity that was caused by extensive damage to peripheral fiber cells located up to 150 m in from the lens capsule, whereas deeper fiber cells appeared unaffected by DIOA exposure. Lower concentrations of DIOA (10 M) revealed that this damage was initiated primarily by the swelling of peripheral fiber cells. In contrast, NPPB-treated lenses exhibited a deeper zone (Ͼ100 m) of cell damage that was initiated by the dilation of the extracellular space between fiber cells. Exposure of lenses to the KCC activator NEM caused cell shrinkage in peripheral fiber cells but extensive cell swelling in deeper fiber cells. Peripheral cell swelling caused a differential recruitment of KCC isoforms from a cytoplasmic pool to the plasma membrane. DIOA-induced cell swelling increased the association of KCC4 with membrane, whereas hypotonic cell swelling dramatically increased the association of KCC1 with the membrane. CONCLUSIONS. The rat lens expresses three KCC transporter isoforms (KCC1, -3, and -4) in a differentiation-dependent manner. Modulation of transporter activity and subcellular localization suggests that multiple KCC transporters mediate KCl efflux in peripheral fiber cells in a dynamic fashion. These results indicate that, in addition to Cl Ϫ channels, KCC transporters play a role in mediating a circulating flux of Cl T he maintenance of lens transparency is critically dependent on the ability of the lens to regulate the volume of its constituent fiber cells. Fiber cell swelling or shrinkage not only disrupts the regular arrangement of these cells, but also changes the solubility of the crystallin proteins, thereby producing light scattering and eventually lens cataract. 1 Earlier studies have shown that lenses placed in hypotonic medium initially swell, but then undergo a regulatory volume decrease (RVD) through the loss of K ϩ and Cl Ϫ ions. 2 More recently, the role that Cl Ϫ ions play in this process has been further investigated by culturing rat lenses in the presence of a range of Cl Ϫ channel inhibitors, including 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). 3 This indicates that, under normal isotonic conditions, a constitutively active flux of Cl Ϫ ions exists in the lens that regulates fiber cell volume and thereby maintains lens transparency. Mathias et al. 4 NPPB-treated lenses exhibited two distinct damage phenotypes: an initial deeper (150 -300 m) zone of extracellular space dilations, due to the blockage of Cl Ϫ influx, and a more peripheral zone of mild cell swelling, caused by the inhibition of Cl Ϫ efflux. To verify the involvement of chloride channels in these two processes, Webb et al. 7 conducted patch clamp experiments on isolated fiber cells. Fiber cells that were greater than 120 m in length originated from the zone of extracellular space dilations and exhibited an outwardly rectifying chloride conductance that was blocked by Cl Ϫ channel inhibitors. In contrast, shorter, more peripheral fiber cells isolated from the zone of cell swelling appeared to lack constitutively active Cl Ϫ channels (Donaldson PJ, et al. IOVS 2005;46:ARVO E-Abstract 1129)

What is the risk of death or severe harm due to bone cement implantation syndrome among patients undergoing hip hemiarthroplasty for fractured neck of femur? A patient safety surveillance study.

OBJECTIVE: To estimate the risk of death or severe harm due to bone cement implantation syndrome (BCIS) among patients undergoing hip hemiarthroplasty for fractured neck of femur. SETTING: Hospitals providing secondary and tertiary care throughout the National Health Service (NHS) in England and Wales. PARTICIPANTS: Cases reported to the National Reporting and Learning System (NRLS) in which the reporter clearly describes severe acute patient deterioration associated with cement use in hip hemiarthroplasty for fractured neck of femur (assessed independently by two reviewers). OUTCOME MEASURES: Primary-number of reported deaths, cardiac arrests and periarrests per year. Secondary-timing of deterioration and outcome in relation to cement insertion. RESULTS: Between 2005 and 2012, the NRLS received 62 reports that clearly describe death or severe harm associated with the use of cement in hip hemiarthroplasty for fractured neck of femur. There was one such incident for every 2900 hemiarthroplasties for fractured neck of femur during the period. Of the 62 reports, 41 patients died, 14 were resuscitated from cardiac arrest and 7 from periarrest. Most reports (55/62, 89%) describe acute deterioration occurring during or within a few minutes of cement insertion. The vast majority of deaths (33/41, 80%) occurred on the operating table. CONCLUSIONS: These reports provide narrative evidence from England and Wales that cement use in hip hemiarthroplasty for fractured neck of femur is associated with instances of perioperative death or severe harm consistent with BCIS. In 2009, the National Patient Safety Agency publicised this issue and encouraged the use of mitigation measures. Three-quarters of the deaths in this study have occurred since that alert, suggesting incomplete implementation or effectiveness of those mitigation measures. There is a need for stronger evidence that weighs the risks and benefits of cement in hip hemiarthroplasty for fractured neck of femur

Hamiltonian 2-forms in Kahler geometry, III Extremal metrics and stability

This paper concerns the explicit construction of extremal Kaehler metrics on total spaces of projective bundles, which have been studied in many places. We present a unified approach, motivated by the theory of hamiltonian 2-forms (as introduced and studied in previous papers in the series) but this paper is largely independent of that theory. We obtain a characterization, on a large family of projective bundles, of those `admissible' Kaehler classes (i.e., the ones compatible with the bundle structure in a way we make precise) which contain an extremal Kaehler metric. In many cases, such as on geometrically ruled surfaces, every Kaehler class is admissible. In particular, our results complete the classification of extremal Kaehler metrics on geometrically ruled surfaces, answering several long-standing questions. We also find that our characterization agrees with a notion of K-stability for admissible Kaehler classes. Our examples and nonexistence results therefore provide a fertile testing ground for the rapidly developing theory of stability for projective varieties, and we discuss some of the ramifications. In particular we obtain examples of projective varieties which are destabilized by a non-algebraic degeneration.Comment: 40 pages, sequel to math.DG/0401320 and math.DG/0202280, but largely self-contained; partially replaces and extends math.DG/050151

MP20, the second most abundant lens membrane protein and member of the tetraspanin superfamily, joins the list of ligands of galectin-3

BACKGROUND: Although MP20 is the second most highly expressed membrane protein in the lens its function remains an enigma. Putative functions for MP20 have recently been inferred from its assignment to the tetraspanin superfamily of integral membrane proteins. Members of this family have been shown to be involved in cellular proliferation, differentiation, migration, and adhesion. In this study, we show that MP20 associates with galectin-3, a known adhesion modulator. RESULTS: MP20 and galectin-3 co-localized in selected areas of the lens fiber cell plasma membrane. Individually, these proteins purified with apparent molecular masses of 60 kDa and 22 kDa, respectively. A 104 kDa complex was formed in vitro upon mixing the purified proteins. A 102 kDa complex of MP20 and galectin-3 could also be isolated from detergent-solubilized native fiber cell membranes. Binding between MP20 and galectin-3 was disrupted by lactose suggesting the lectin site was involved in the interaction. CONCLUSIONS: MP20 adds to a growing list of ligands of galectin-3 and appears to be the first representative of the tetraspanin superfamily identified to possess this specificity

Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

<p>Abstract</p> <p>Background</p> <p>A symposium on the mechanisms of action of inhaled airborne particulate matter (PM), pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental Protection Agency (EPA) Conference Center in Research Triangle Park, North Carolina. The meeting was the eighth in a series of transatlantic conferences first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit (1979), that have fostered long-standing collaborations between researchers in the fields of mineralogy, cell and molecular biology, pathology, toxicology, and environmental/occupational health.</p> <p>Results</p> <p>The goal of this meeting, which was largely supported by a conference grant from the NHLBI, was to assemble a group of clinical and basic research scientists who presented and discussed new data on the mechanistic effects of inhaled particulates on the onset and development of morbidity and mortality in the lung and cardiovascular system. Another outcome of the meeting was the elucidation of a number of host susceptibility factors implicated in adverse health effects associated with inhaled pathogenic particulates.</p> <p>Conclusion</p> <p>New models and data presented supported the paradigm that both genetic and environmental (and occupational) factors affect disease outcomes from inhaled particulates as well as cardiopulmonary responses. These future studies are encouraged to allow the design of appropriate strategies for prevention and treatment of particulate-associated morbidity and mortality, especially in susceptible populations.</p

Inversion symmetric 3-monopoles and the Atiyah-Hitchin manifold

We consider 3-monopoles symmetric under inversion symmetry. We show that the moduli space of these monopoles is an Atiyah-Hitchin submanifold of the 3-monopole moduli space. This allows what is known about 2-monopole dynamics to be translated into results about the dynamics of 3-monopoles. Using a numerical ADHMN construction we compute the monopole energy density at various points on two interesting geodesics. The first is a geodesic over the two-dimensional rounded cone submanifold corresponding to right angle scattering and the second is a closed geodesic for three orbiting monopoles.Comment: latex, 22 pages, 2 figures. To appear in Nonlinearit

2D-infrared spectroscopy of proteins in water : using the solvent thermal response as an internal standard

Ultrafast two-dimensional infrared (2D-IR) spectra can now be obtained in a matter of seconds, opening up the possibility of high-throughput screening applications of relevance to the biomedical and pharmaceutical sectors. Determining quantitative information from 2D-IR spectra recorded on different samples and different instruments is however made difficult by variations in beam alignment, laser intensity, and sample conditions. Recently, we demonstrated that 2D-IR spectroscopy of the protein amide I band can be performed in aqueous (H2O) rather than deuterated (D2O) solvents, and we now report a method that uses the magnitude of the associated thermal response of H2O as an internal normalization standard for 2D-IR spectra. Using the water response, which is temporally separated from the protein signal, to normalize the spectra allows significant reduction of the impact of measurement-to-measurement fluctuations on the data. We demonstrate that this normalization method enables creation of calibration curves for measurement of absolute protein concentrations and facilitates reproducible difference spectroscopy methodologies. These advances make significant progress toward the robust data handling strategies that will be essential for the realization of automated spectral analysis tools for large scale 2D-IR screening studies of protein-containing solutions and biofluids