Electrocatalytic Conversion of Small Molecules Utilizing Concerted Proton-electron Transfer Mediators

Activation of small molecules such as CO2, N2 or organic substrates and their subsequent transformation into complex value-added chemicals by electrocatalysis, utilizing renewable energy sources under ambient conditions, has gained considerable interest in the last few years. However, activation of these chemically inert molecules is hindered by their intrinsically high activation energy barrier presupposing the development of tailored catalytic systems, often precluding selective transformation to the desired target products. Recent studies have shown that the utilization of concerted proton-electron transfer (CPET) mediators (med-H) may facilitate these challenging electrocatalytic reactions

Identification of a novel motif in DNA ligases exemplified by DNA ligase IV

DNA ligase IV is an essential protein that functions in DNA non-homologous end-joining, the major mechanism that rejoins DNA double-strand breaks in mammalian cells. LIG4 syndrome represents a human disorder caused by mutations in DNA ligase IV that lead to impaired but not ablated activity. Thus far, five conserved motifs in DNA ligases have been identified. We previously reported G469E as a mutational change in a LIG4 syndrome patient. G469 does not lie in any of the previously reported motifs. A sequence comparison between DNA ligases led us to identify residues 468¿476 of DNA ligase IV as a further conserved motif, designated motif Va, present in eukaryotic DNA ligases. We carried out mutational analysis of residues within motif Va examining the impact on adenylation, double-stranded ligation, and DNA binding. We interpret our results using the DNA ligase I:DNA crystal structure. Substitution of the glycine at position 468 with an alanine or glutamic acid severely compromises protein activity and stability. Substitution of G469 with an alanine or glutamic acid is better tolerated but still impacts upon activity and protein stability. These finding suggest that G468 and G469 are important for protein stability and provide insight into the hypomorphic nature of the G469E mutation identified in a LIG4 syndrome patient. In contrast, residues 470, 473 and 476 within motif Va can be changed to alanine residues without any impact on DNA binding or adenylation activity. Importantly, however, such mutational changes do impact upon double-stranded ligation activity. Considered in light of the DNA ligase I:DNA crystal structure, our findings suggest that residues 470¿476 function as part of a molecular pincer that maintains the DNA in a conformation that is required for ligation

LUMIO, a Lunar Meteoroid Impacts Observer

Accurate models of the distribution of meteoroids in the Earth-Moon system are needed to predict impacts with space equipment and for safe space exploration. The Moon\u27s lack of atmosphere allows for observation of meteoroid impacts: understanding meteoroids is important for studying asteroids, comets, and near-Earth objects. The Lunar Meteoroid Impacts Observer (LUMIO) is a CubeSat mission designed to detect and characterize meteoroid impacts on the far side of the Moon. It can detect small meteoroids too faint for Earth-based observations. LUMIO operates in a Halo orbit at Earth-Moon L2 using the LUMIO-Cam, an optical instrument detecting visible light flashes. The mission is developed under ESA\u27s General Support Technology Program Fly Element. This work highlights the technical challenges and innovative solutions for the LUMIO platform, designed to meet scientific experiment requirements. The satellite will perform a transfer through a Weak Stability Boundary (WSB) trajectory to reach its final orbit. During nominal operations, LUMIO will detect meteoroids for half the lunar month when the Moon is not completely illuminated. The remaining time will be dedicated to station keeping, orbit determination, and optical navigation using an innovative approach. LUMIO features high-reliability technologies to ensure mission success despite mass, volume, power, and cost constraints

L-asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer

Abstract Recent work identified L-asparaginase (L-ASP) as a putative therapeutic target for ovarian cancer. We suggest that L-ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cell\u2014endothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human microvascular endothelial cells (HMVEC) were exposed to L-ASP at physiologically attainable concentrations and subjected to analyses of endothelial tube formation, invasion, adhesion and the assessment of sialylated proteins involved in matrix-associated and heterotypic cell adhesion. Marked reduction in HMVEC tube formation in vitro, HMVEC and ovarian cancer cell invasion, and heterotypic cell-cell and cell-matrix adhesion was observed (P < 0.05\u20130.0001). These effects were associated with reduced binding to f1integrin, activation of FAK, and cell surface sialyl LewisX (sLex) expression. No reduction in HMVEC E-selectin expression was seen consistent with the unidirectional inhibitory actions observed. L-ASP concentrations were non-toxic to either ovarian cancer or HMVEC lines in the time frame of the assays. However, early changes of autophagy were observed in both cell types with induction of ATG12, beclin-1, and cleavage of LC-3, indicating cell injury did occur. These data and the known mechanism of action of L-ASP on glycosylation of nascent proteins suggest that L-ASP reduces of ovarian cancer dissemination and progression through modification of its microenvironment. The reduction of ovarian cancer cell surface sLex inhibits interaction with HMVEC and thus HMVEC differentiation into tubes, inhibits interactio

The Large Magellanic Cloud globular cluster NGC 1866: new data, new models, new analysis

We present a new deep (down to V ~ 24) photometry of a wide region (6'x 6') around the LMC globular cluster NGC1866: our sample is complete, down to 3 mag below the brightest MS star. Detailed comparisons with various theoretical scenarios using models computed with the evolutionary code FRANEC have been done reaching the following conclusions: both standard models (i.e. computed by adopting the Schwarzschild criterion to fix the border of the convective core) and models with an enlarged convective core (overshooting) lead to a fair fit of the MS but are not able to reproduce the luminosity and/or the number of He burning giants. Models including a fraction of 30% of binaries leads to a good fit both to the MS luminosity function and to the He clump, if standards models are considered, for a visual distance modulus (m-M)v = 18.8, age t ~ 100 Myr and mass function slope alpha ~ 2.4, thus largely removing the "classical" discrepancy between observed and predicted number of stars in the He burning clump. The fit obtained with models computed with an enlarged convective core gets worse when a binary component is taken into account, because the presence of binary systems increases the existing discrepancy between the observed and predicted clump luminosity. As a consequence of this analysis, we conclude that the next step towards a proper understanding of NGC 1866, and similar clusters, must include the accurate determination of the frequency of binary systems that will be hopefully performed with the incoming Cycle 8 HST observations of NGC~1866.Comment: AASTEX 5.0, 33 pages, 35 figures. Two tables of photometry and full resolution figures available on request from the first author ([email protected]). Accepted on A

Approximate Analytical Model for the Squeeze-Film Lubrication of the Human Ankle Joint with Synovial Fluid Filtrated by Articular Cartilage

The aim of this article is to propose an analytical approximate squeeze-film lubrication model of the human ankle joint for a quick assessment of the synovial pressure field and the load carrying due to the squeeze motion. The model starts from the theory of boosted lubrication for the human articular joints lubrication (Walker et al., Rheum Dis 27:512–520, 1968; Maroudas, Lubrication and wear in joints. Sector, London, 1969) and takes into account the fluid transport across the articular cartilage using Darcy’s equation to depict the synovial fluid motion through a porous cartilage matrix. The human ankle joint is assumed to be cylindrical enabling motion in the sagittal plane only. The proposed model is based on a modified Reynolds equation; its integration allows to obtain a quick assessment on the synovial pressure field showing a good agreement with those obtained numerically (Hlavacek, J Biomech 33:1415–1422, 2000). The analytical integration allows the closed form description of the synovial fluid film force and the calculation of the unsteady gap thickness

Interaction between the Rev1 C-Terminal Domain and the PolD3 Subunit of Polζ Suggests a Mechanism of Polymerase Exchange upon Rev1/Polζ-Dependent Translesion Synthesis

Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first step, a Y-family TLS enzyme, typically Polη, Polι, or Polκ, inserts a nucleotide across a DNA lesion. In the second step, a four-subunit B-family DNA polymerase Polζ (Rev3/Rev7/PolD2/PolD3 complex) extends the distorted DNA primer-template. The coordinated action of error-prone TLS enzymes is regulated through their interactions with the two scaffold proteins, the sliding clamp PCNA and the TLS polymerase Rev1. Rev1 interactions with all other TLS enzymes are mediated by its C-terminal domain (Rev1-CT), which can simultaneously bind the Rev7 subunit of Polζ and Rev1-interacting regions (RIRs) from Polη, Polι, or Polκ. In this work, we identified a previously unknown RIR motif in the C-terminal part of PolD3 subunit of Polζ whose interaction with the Rev1-CT is among the tightest mediated by RIR motifs. Three-dimensional structure of the Rev1-CT/PolD3-RIR complex determined by NMR spectroscopy revealed a structural basis for the relatively high affinity of this interaction. The unexpected discovery of PolD3-RIR motif suggests a mechanism of “inserter” to “extender” DNA polymerase switch upon Rev1/Polζ-dependent TLS, in which the PolD3-RIR binding to the Rev1-CT (i) helps displace the “inserter” Polη, Polι, or Polκ from its complex with Rev1, and (ii) facilitates assembly of the four-subunit “extender” Polζ through simultaneous interaction of Rev1-CT with Rev7 and PolD3 subunits

Geminate and nongeminate recombination of triplet excitons formed by singlet fission.

We report the simultaneous observation of geminate and nongeminate triplet-triplet annihilation in a solution-processable small molecule TIPS-tetracene undergoing singlet exciton fission. Using optically detected magnetic resonance, we identify recombination of triplet pairs directly following singlet fission, as well as recombination of triplet excitons undergoing bimolecular triplet-triplet annihilation. We show that the two processes give rise to distinct magnetic resonance spectra, and estimate the interaction between geminate triplet excitons to be 60 neV.EPSRC [grant no. EP/J017361/1 and EP/G060738/1]. E. Oppenheimer Foundation and St. Catherine's College, Cambridge. NSF [CMMI- 1255494].This is the author accepted manuscript. The final version is available at http://journals.aps.org/prl/abstract/10.1103/PhysRevLett.112.238701

Current-Fed Isolated DC/DC Converter for Future Aerospace Microgrids

High-performance power conversion equipment is currently gaining an increasing interest for aircraft applications. In particular, isolated bidirectional dc/dc converters are often proposed for modern aircraft distribution systems. A current-fed isolated dc/dc converter, named active-clamp active-bridge topology, is identified as the most promising for the proposed application, interfacing a 270-V dc network with a 28-V dc network. A comparison between the selected topology and the well-known dual-active-bridge topology has been carried out and an experimental prototype has been manufactured for the selected conversion architecture. Simulation and experimental results are provided in order to validate the tradeoff and the design of the proposed converter