Redox-inactive metals modulate the reduction potential in heterometallic manganese–oxido clusters

Redox-inactive metals are found in biological and heterogeneous water oxidation catalysts, but, at present, their roles in catalysis are not well understood. Here, we report a series of high-oxidation-state tetranuclear-dioxido clusters comprising three manganese centres and a redox-inactive metal (M). Crystallographic studies show an unprecedented Mn_3M(µ_4-O)(µ_2-O) core that remains intact on changing M or the manganese oxidation state. Electrochemical studies reveal that the reduction potentials span a window of 700 mV and are dependent on the Lewis acidity of the second metal. With the pK_a of the redox-inactive metal–aqua complex as a measure of Lewis acidity, these compounds demonstrate a linear dependence between reduction potential and acidity with a slope of ∼100 mV per pK_a unit. The Sr^(2+) and Ca^(2+) compounds show similar potentials, an observation that correlates with the behaviour of the oxygen-evolving complex of photosystem II, which is active only if one of these two metals is present

Role of oxido incorporation and ligand lability in expanding redox accessibility of structurally related Mn4 clusters

Photosystem II supports four manganese centers through nine oxidation states from manganese(II) during assembly through to the most oxidized state before O_2 formation and release. The protein-based carboxylate and imidazole ligands allow for significant changes of the coordination environment during the incorporation of hydroxido and oxido ligands upon oxidation of the metal centers. We report the synthesis and characterization of a series of tetramanganese complexes in four of the six oxidation states from Mn^(II)_(3)Mn^III to Mn^(III)_(2)Mn^(IV)_2 with the same ligand framework (L) by incorporating four oxido ligands. A 1,3,5-triarylbenzene framework appended with six pyridyl and three alkoxy groups was utilized along with three acetate anions to access tetramanganese complexes, Mn_(4)O_x, with x = 1, 2, 3, and 4. Alongside two previously reported complexes, four new clusters in various states were isolated and characterized by crystallography, and four were observed electrochemically, thus accessing the eight oxidation states from Mn^(II)_4 to Mn^(III)Mn^(IV)_3. This structurally related series of compounds was characterized by EXAFS, XANES, EPR, magnetism, and cyclic voltammetry. Similar to the ligands in the active site of the protein, the ancillary ligand (L) is preserved throughout the series and changes its binding mode between the low and high oxido-content clusters. Implications for the rational assembly and properties of high oxidation state metal–oxido clusters are presented

Molecular Mixed-Metal Manganese Oxido Cubanes as Precursors to Heterogeneous Oxygen Evolution Catalysts

Well-defined mixed-metal [CoMn_3O_4] and [NiMn_3O_4] cubane complexes were synthesized and used as precursors for heterogeneous oxygen evolution reaction (OER) electrocatalysts. The discrete clusters were dropcasted onto glassy carbon (GC) and indium tin oxide (ITO) electrodes, and the OER activities of the resulting films were evaluated. The catalytic surfaces were analyzed by various techniques to gain insight into the structure-function relationships of the electrocatalysts’ heterometallic composition. Depending on preparation conditions, the Co-Mn oxide was found to change metal composition during catalysis, while the Ni–Mn oxides maintained the NiMn_3 ratio. XAS studies provided structural insights indicating that the electrocatalysts are different from the molecular precursors, but that the original NiMn_3O_4 cubane-like geometry was maintained in the absence of thermal treatment (2-Ni). In contrast, the thermally generated 3-Ni develops an oxide-like extended structure. Both 2-Ni and 3-Ni undergo structural changes upon electrolysis, but they do not convert into the same material. The observed structural motifs in these heterogeneous electrocatalysts are reminiscent of the biological oxygen-evolving complex in Photosystem II, including the MMn_3O_4 cubane moiety. The reported studies demonstrate the use of discrete heterometallic oxide clusters as precursors for heterogeneous water oxidation catalysts of novel composition and the distinct behavior of two sets of mixed metal oxides

The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial

Background: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10+0-20+0weeks, and BMI ≥ 25 kg/m2were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. Results: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group 11261.19±14573.97 versus Standard Care Group 11306.70±14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to$45,000. Conclusions: Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes

Probing the heme structure and environment of bacterial Heme-Nitric oxide/OXygen binding domains with resonance Raman spectroscopy

The Heme-Nitric oxide/OXygen binding (H-NOX) domain encompasses a family of proteins closely related (≤ 40% sequence identity) to the heme domain of soluble guanylate cyclase (sGC), the eukaryotic enzyme receptor for NO [1, 2]. sGC discriminates between NO and O2, and exclusively binds NO even in the presence of excess O2. Although some H-NOX domains have ligand binding properties that are identical to sGC, others additionally bind O2, including the atypical sGCs from Drosophila melanogaster and Caenorhabditis elegans [1, 3, 4]. The molecular basis of this ligand selectivity is not fully understood. In order to better understand the H-NOX domain, resonance Raman (RR) spectroscopy was employed in combination with isotopic substitution and site-directed mutagenesis to probe the heme pocket in Thermoanaerobacter tengcongensis (Tt H-NOX) as a model system for this family of heme proteins. Thus, the expression, purification, and RR characterization of Tt H-NOX and selected mutants were performed to elucidate the heme environmental properties that influence ligand binding.A striking feature of the O2-bound WT Tt H-NOX crystal structure is the presence of a distorted heme molecule [5]. RR investigation of Tt H-NOX proteins containing mutations at key conserved residues, Ile-5 and Pro-115, determined that the most dramatic heme conformational changes occurred in the O2-bound forms, and that the single P115A mutation generated a significantly relaxed chromophore. Decreased RR intensities were observed for several out-of-plane modes in the 400-750 cm-1 region known to be sensitive to ruffling and saddling deformations, as well as increased vibrational frequencies for the core heme skeletal modes. These changes demonstrated that the P115A heme conformation was considerably more relaxed than WT, with increased flexibility within the protein pocket that allowed for rapid sampling of alternate conformations.Another remarkable feature of this family is the spectroscopic observation of an unusually high ν(C-O) frequency. To elucidate the interactions responsible for this property, mutations were made in Tt H-NOX to probe the distal pocket, the conserved Tyr-Ser-Arg (YxSxR) motif, and the heme-linkage site (His-102). RR spectra of these mutants indicated that H-bonding interactions between these residues and the heme significantly affected the CO bond by increasing the back-donation of the FeII dπ electrons into the CO π* orbitals. The most significant change occurred upon disruption of the H-bonds between the YxSxR motif and the heme propionate groups, producing two dominant CO-bound heme conformations; one was structurally similar to WT, and the other conformer displayed ν(C-O) downshifts of up to ~70 cm-1. Based on these shifts, the most important factor contributing to the C-O stretching mode may be the neutralization of the negative charges on the propionate groups via the strictly conserved YxSxR motif.Finally, the role of the Tt H-NOX binding pocket in stabilizing the O2 complex was investigated. Evidence of H-bonds to the bound O2 was demonstrated in the RR spectra of Trp-9 and Tyr-140 mutants; the disruption of the H-bond network in these mutations increased ν(Fe-O2) upon returning electron density to the Fe-O2 bond. In contrast, the addition of steric bulk to the H-NOX pocket decreased the ν(Fe-O2) frequency relative to the WT protein. These shifts suggested that the bulky distal residues forced the H-NOX binding pocket into a more open position that increased the distance between Tyr-140 and the O2, thereby weakening this crucial H-bond. Thus, two distinct factors influence the ν(Fe-O2) in Tt H-NOX: (i) electrostatic effects from H-bonding with Tyr-140, which increased the ν(Fe-O2) frequency upon its removal; and (ii) steric effects which decreased ν(Fe-O2) due to bond lengthening from a more loosely held O2 ligand.In summary, this work presents a comparative analysis of the heme environmental effects in Tt H-NOX. By directly probing the interactions between the heme chromophore and the protein pocket through a combination of RR spectroscopy and site-directed mutagenesis, this study may elucidate the biochemical properties of these H-NOX domains, and bring insight into the relationship between heme structure and protein function in this family

Velocity and Color Estimation Using Event-Based Clustering

International audienceEvent-based clustering provides a low-power embedded solution for low-level feature extraction in a scene. The algorithm utilizes the non-uniform sampling capability of event-based image sensors to measure local intensity variations within a scene. Consequently, the clustering algorithm forms similar event groups while simultaneously estimating their attributes. This work proposes taking advantage of additional event information in order to provide new attributes for further processing. We elaborate on the estimation of the object velocity using the mean motion of the cluster. Next, we are examining a novel form of events, which includes intensity measurement of the color at the concerned pixel. These events may be processed to estimate the rough color of a cluster, or the color distribution in a cluster. Lastly, this paper presents some applications that utilize these features. The resulting algorithms are applied and exercised thanks to a custom event-based simulator, which generates videos of outdoor scenes. The velocity estimation methods provide satisfactory results with a trade-off between accuracy and convergence speed. Regarding color estimation, the luminance estimation is challenging in the test cases, while the chrominance is precisely estimated. The estimated quantities are adequate for accurately classifying objects into predefined categories.</p

An improved event-by-event clustering algorithm for noisy acquisition

International audienceEvent-based image sensors are a new class of sensors developed thanks to non-uniform sampling and asynchronous technology, which overcomes many image sensor limitations such as a high throughput or a huge power consumption. As their behavior and outputs are really different from traditional image sensors, the produced data stream imposes to completely rethink image processing. Indeed, dedicated algorithms are mandatory to take advantage of this specific data stream, known as Address Event Representation (AER). This paper presents an improved and dedicated event-by-event clustering algorithm allowing the object detection in a noisy environment which is still performant with a SNR of 1/4. We measure high recall and precision for different simulated scenarios with multiple objects and show an improvement compared to the previous algorithm. The approach especially demonstrates a low computational complexity and a reduced memory footprint, which is perfectly suited for low-cost and low-power embedded image sensing applications.</p

Low-Throughput Event-Based Image Sensors and Processing

International audienceThis paper presents new kinds of image sensors based on TFS (Time to First Spike) pixels and DVS (Dynamic Vision Sensor) pixels, which take advantage of non-uniform sampling and redundancy suppression to reduce the data throughput. The DVS pixels only detect a luminance variation, while TFS pixels quantized luminance by measuring the required time to cross a threshold. Such image sensors output requests through an Address Event Representation (AER), which helps to reduce the data stream The resulting event bitstream is composed by time, position, polarity, and magnitude information. Such a bitstream offers new possibilities for image processing such as event-by-event object tracking. In particular, we propose some processing to cluster events, filter noise and extract other useful features, such as a velocity estimation.</p