Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases

Iron is an especially important redox-active cofactor in biology because of its ability to mediate reactions with atmospheric O₂. Iron-dependent oxygenases exploit this earth-abundant transition metal for the insertion of oxygen atoms into organic compounds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C–H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiological transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges associated with engineering these platforms and comment on their roles in biocatalysis moving forward

Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases

Iron is an especially important redox-active cofactor in biology because of its ability to mediate reactions with atmospheric O₂. Iron-dependent oxygenases exploit this earth-abundant transition metal for the insertion of oxygen atoms into organic compounds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C–H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiological transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges associated with engineering these platforms and comment on their roles in biocatalysis moving forward

Evolutionary Signatures In The Formation Of Low-Mass Protostars. II. Toward Reconciling Models And Observations

A long-standing problem in low-mass star formation is the "luminosity problem," whereby protostars are underluminous compared to the accretion luminosity expected both from theoretical collapse calculations and arguments based on the minimum accretion rate necessary to form a star within the embedded phase duration. Motivated by this luminosity problem, we present a set of evolutionary models describing the collapse of low-mass, dense cores into protostars. We use as our starting point the evolutionary model following the inside-out collapse of a singular isothermal sphere as presented by Young & Evans. We calculate the radiative transfer of the collapsing core throughout the full duration of the collapse in two dimensions. From the resulting spectral energy distributions, we calculate standard observational signatures (L(bol), T(bol), L(bol)/L(smm)) to directly compare to observations. We incorporate several modifications and additions to the original Young & Evans model in an effort to better match observations with model predictions; we include (1) the opacity from scattering in the radiative transfer, (2) a circumstellar disk directly in the two-dimensional radiative transfer, (3) a two-dimensional envelope structure, taking into account the effects of rotation, (4) mass-loss and the opening of outflow cavities, and (5) a simple treatment of episodic mass accretion. We find that scattering, two-dimensional geometry, mass-loss, and outflow cavities all affect the model predictions, as expected, but none resolve the luminosity problem. On the other hand, we find that a cycle of episodic mass accretion similar to that predicted by recent theoretical work can resolve this problem and bring the model predictions into better agreement with observations. Standard assumptions about the interplay between mass accretion and mass loss in our model give star formation efficiencies consistent with recent observations that compare the core mass function and stellar initial mass function. Finally, the combination of outflow cavities and episodic mass accretion reduces the connection between observational class and physical stage to the point where neither of the two commonly used observational signatures (T(bol) and L(bol)/L(smm)) can be considered reliable indicators of physical stage.NASA 1224608, 1288664, 1288658, RSA 1377304, NNX 07-AJ72GNSF AST0607793UT Austin University Continuing FellowshipAstronom

Driving success towards zero carbon energy targets for UK's Local Authorities

This paper draws on three case studies which show feasible and economic results in meeting net zero carbon emissions targets through Smart Local Energy Systems (SLES) in different localities across England, exploring opportunities to utilise waste heat from industry. They are based on the GreenSCIES model for which the blueprint was developed in London, Study 1. It consists of a fifth generation (5G) ambient loop district heat network using waste heat from a data centre, integrated with electric vehicle charging, storage and solar PV. The network includes decentralised heat pumps and allows for (i) heat sharing between buildings and (ii) applications for heat recovery from local sources. Study 2 is based on a heat network with waste heat from a foundry and some cooling supply and heat storage in the aquifer. Study 3 explored waste heat from a glassworks and considered mine workings for providing heat storage. These SLES projects illustrate how to integrate local waste heat sources in 3G and 4G heat networks, adapting the original GreenSCIES concept, providing pathways towards net zero carbon for a diverse range of urban locations with different waste heat sources, and further demonstrate the importance of collaboration between researchers, local government and industry

Centrifugal terms in the WKB approximation and semiclassical quantization of hydrogen

A systematic semiclassical expansion of the hydrogen problem about the classical Kepler problem is shown to yield remarkably accurate results. Ad hoc changes of the centrifugal term, such as the standard Langer modification where the factor l(l+1) is replaced by (l+1/2)^2, are avoided. The semiclassical energy levels are shown to be exact to first order in $\hbar$ with all higher order contributions vanishing. The wave functions and dipole matrix elements are also discussed.Comment: 5 pages, to appear in Phys. Rev.

An investigation of the existence of a surface water layer on aircraft radomes during simulated flight in heavy precipitation

An experiment to investigate the electromagnetic attenuation effects of an impacting water spray on an aircraft weather radome was conducted in Langley's 4 X 7 m. wind tunnel equipped with a water spray system. Results indicate no significant liquid water film formed at the stagnation point of the radome under the test conditions. However, a water sheath was observed standing away from the radome surface, which could possibly have significant attenuation properties of its own. Due to the lack of fidelity in modeling both the natural environment with the tunnel apparatus and the water sheath, it is recommended that further studies be undertaken to better define the water distribution in the vicinity of the radome and measure its effect on weather radar performance

The WKB Approximation without Divergences

In this paper, the WKB approximation to the scattering problem is developed without the divergences which usually appear at the classical turning points. A detailed procedure of complexification is shown to generate results identical to the usual WKB prescription but without the cumbersome connection formulas.Comment: 13 pages, TeX file, to appear in Int. J. Theor. Phy

Chronic pain through COVID

Objectives: To identify good practice in the community management of chronic pain, and to understand the perspective of a group of healthcare service users towards the management of chronic pain using technology during the COVID-19 pandemic. Methods: Forty-five people, recruited via social media and Pain Association Scotland, participated in three focus groups hosted over Zoom. Focus groups were conducted using semi-structured questions to guide the conversation. Data were analysed using Ritchie / Spencer's Framework Analysis. Results: The participants shared observations of their experiences of remotely supported chronic pain services and insights into the potential for future chronic pain care provision. Experiences were in the majority positive with some describing their rapid engagement with technology during the COVID pandemic. Conclusion: Results suggest there is strong potential for telehealth to complement and support existing provision of pain management services

The Importance of Heat Pump COP in the Economics of 5th Generation District Heating and Cooling Networks

This paper describes the investigation of heat pumps for GreenSCIES, a 5th Generation heat network in Islington, London. The paper describes the GreenSCIES concept integrating Mobility, Power and Heat into a local energy system. At the heart of the system is a 5th generation heat network, which utilises an ambient heat network to capture secondary heat and share heat between different applications. The GreenSCIES network, technology utilised and buildings connected are described. Heat pumps are used to amplify the temperature of the ambient loop to deliver heat at the required temperature in connected buildings. A number of different heat pumps using different refrigerants and configurations were appraised in this study. This considered the performance, safety, environmental impact, operational and capital expenditure point of view. The study shows the importance of heat pump COP on the economics of operating the system and suggests innovative series arrangements in order to improve performance and economics