Binding prediction of multi-domain cellulases with a dual-CNN

Cellulases hold great promise for the production of biofuels and biochemicals. However, they are modular enzymes acting on a complex heterogeneous substrate. Because of this complexity, the computational prediction of their catalytic properties remains scarce, which restricts both enzyme discovery and enzyme design. Here, we present a dual-input convolutional neural network to predict the binding of multi-domain enzymes. This regression model outperformed previous molecular dynamics-based methods for binding prediction for cellulases in a fraction of the time. Also, we show that when changed to a classification problem, the same network can be back-propagated to suggest mutations to improve enzyme binding. A similar approach could increase our understanding of the structure-activity relationship of enzymes, and suggest new promising mutations for enzyme design using explainable artificial intelligence

Towards net zero CO2 in 2050: an emission reduction pathway for organic soils in Germany

The Paris Agreement reflects the global endeavour to limit the increase of global average temperature to 2 °C, better 1.5 °C above pre-industrial levels to prevent dangerous climate change. This requires that global anthropogenic net carbon dioxide (CO2) emissions are reduced to zero around 2050. The German Climate Protection Plan substantiates this goal and explicitly mentions peatlands, which make up 5 % of the total area under land use and emit 5.7 % of total annual greenhouse gas emissions in Germany. Based on inventory reporting and assumptions of land use change probability, we have developed emission reduction pathways for organic soils in Germany that on a national level comply with the IPCC 1.5 °C pathways. The more gradual pathway 1 requires the following interim (2030, 2040) and ultimate (2050) milestones: Cropland use stopped and all Cropland converted to Grassland by 2030; Water tables raised to the soil surface on 15 % / 60 % / 100 % of all Grassland, on 50 % / 75 % / 100 % of all Forest land, and ultimately on 2/3 of all Settlements and on 100 % of all Wetlands. Also a more direct pathway 2 without interim ‘moist’ water tables and the climate effect (radiative forcing) of different scenarios is presente

A new approach to electromagnetic wave tails on a curved spacetime

We present an alternative method for constructing the exact and approximate solutions of electromagnetic wave equations whose source terms are arbitrary order multipoles on a curved spacetime. The developed method is based on the higher-order Green's functions for wave equations which are defined as distributions that satisfy wave equations with the corresponding order covariant derivatives of the Dirac delta function as the source terms. The constructed solution is applied to the study of various geometric effects on the generation and propagation of electromagnetic wave tails to first order in the Riemann tensor. Generally the received radiation tail occurs after a time delay which represents geometrical backscattering by the central gravitational source. It is shown that the truly nonlocal wave-propagation correction (the tail term) takes a universal form which is independent of multipole order. In a particular case, if the radiation pulse is generated by the source during a finite time interval, the tail term after the primary pulse is entirely determined by the energy-momentum vector of the gravitational field source: the form of the tail term is independent of the multipole structure of the gravitational source. We apply the results to a compact binary system and conclude that under certain conditions the tail energy can be a noticeable fraction of the primary pulse energy. We argue that the wave tails should be carefully considered in energy calculations of such systems.Comment: RevTex, 28 pages, 5 eps figures, http://www.tpu.ee/~tony/texdocs/, 4 changes made (pp. 2, 4, 22, 24), 2 references adde

Avalanche dynamics, surface roughening and self-organized criticality - experiments on a 3 dimensional pile of rice

We present a two-dimensional system which exhibits features of self-organized criticality. The avalanches which occur on the surface of a pile of rice are found to exhibit finite size scaling in their probability distribution. The critical exponents are $\tau$ = 1.21(2) for the avalanche size distribution and $D$ = 1.99(2) for the cut-off size. Furthermore the geometry of the avalanches is studied leading to a fractal dimension of the active sites of $d_B$ = 1.58(2). Using a set of scaling relations, we can calculate the roughness exponent $\alpha = D - d_B$ = 0.41(3) and the dynamic exponent $z = D(2 - \tau)$ = 1.56(8). This result is compared with that obtained from a power spectrum analysis of the surface roughness, which yields $\alpha$ = 0.42(3) and $z$ = 1.5(1) in excellent agreement with those obtained from the scaling relations.Comment: 7 pages, 8 figures, accepted for publication in PR

Glucagon-like Peptide 1 Conjugated to Recombinant Human Serum Albumin Variants with Modified Neonatal Fc Receptor Binding Properties. Impact on Molecular Structure and Half-Life

Glucagon-like peptide 1 (GLP-1) is a small incretin hormone stimulated by food intake, resulting in an amplification of the insulin response. Though GLP-1 is interesting as a drug candidate for the treatment of type 2 diabetes mellitus, its short plasma half-life of <3 min limits its clinical use. A strategy for extending the half-life of GLP-1 utilizes the long half-life of human serum albumin (HSA) by combining the two via chemical conjugation or genetic fusion. HSA has a plasma half-life of around 21 days because of its interaction with the neonatal Fc receptor (FcRn) expressed in endothelial cells of blood vessels, which rescues circulating HSA from lysosomal degradation. We have conjugated GLP-1 to C34 of native sequence recombinant HSA (rHSA) and two rHSA variants, one with increased and one with decreased binding affinity for human FcRn. We have investigated the impact of conjugation on FcRn binding affinities, GLP-1 potency, and pharmacokinetics, combined with the solution structure of the rHSA variants and GLP-1–albumin conjugates. The solution structures, determined by small-angle X-ray scattering, show the GLP-1 pointing away from the surface of rHSA. Combining the solution structures with the available structural information about the FcRn and GLP-1 receptor obtained from X-ray crystallography, we can explain the observed <i>in vitro</i> and <i>in vivo</i> behavior. We conclude that the conjugation of GLP-1 to rHSA does not affect the interaction between rHSA and FcRn, while the observed decrease in the potency of GLP-1 can be explained by a steric hindrance of binding of GLP-1 to its receptor

Active afforestation of drained peatlands is not a viable option under the EU Nature Restoration Law

The EU Nature Restoration Law (NRL) is critical in restoring degraded ecosystems. However, active afforestation of degraded peatlands has been suggested by some as a restoration measure under the NRL. Here, we discuss the current state of scientific evidence on the climate mitigation effects of peatlands under forestry and its limitations, uncertainties and evidence gaps. Based on this discussion we conclude: Afforestation of drained peatlands, while maintaining their drained state, is not equivalent to ecosystem restoration. This approach will not restore the peatland ecosystem's flora, fauna, and functions. There is insufficient evidence to support the long-term climate change mitigation benefits of active afforestation of drained peatlands. Most studies only focus on the short-term gains in standing biomass and rarely explore the full life cycle emissions associated with afforestation of drained peatlands. Thus, it is unclear whether the CO2 sequestration of a forest on drained peatland can offset the carbon loss from the peat over the long term. In some ecosystems, such as abandoned or certain cutaway peatlands, afforestation may provide short-term benefits for climate change mitigation compared to taking no action. However, this approach violates the concept of sustainability by sacrificing the most space-effective carbon store of the terrestrial biosphere, the long-term peat store, for a shorter-term, less space-effective, and more vulnerable carbon store, namely tree biomass. Consequently, active afforestation of drained peatlands is not a viable option for climate mitigation under the EU Nature Restoration Law and might even impede future rewetting/restoration efforts. To restore degraded peatlands, hydrological conditions must first be improved, primarily through rewetting