Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids

Recent developments in Origins of Life research have focused on substantiating the narrative of an abiotic emergence of nucleic acids from organic molecules of low molecular weight, a paradigm that typically sidelines the roles of peptides. Nevertheless, the simple synthesis of amino acids, the facile nature of their activation and condensation, their ability to recognize metals and cofactors and their remarkable capacity to self-assemble make peptides (and their analogues) favourable candidates for one of the earliest functional polymers. In this mini-review, we explore the ramifications of this hypothesis. Diverse lines of research in molecular biology, bioinformatics, geochemistry, biophysics and astrobiology provide clues about the progression and early evolution of proteins, and lend credence to the idea that early peptides served many central prebiotic roles before they were encodable by a polynucleotide template, in a putative ‘peptide-polynucleotide stage’. For example, early peptides and mini-proteins could have served as catalysts, compartments and structural hubs. In sum, we shed light on the role of early peptides and small proteins before and during the nucleotide world, in which nascent life fully grasped the potential of primordial proteins, and which has left an imprint on the idiosyncratic properties of extant proteins.     

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide

The selectivity of encapsulation of leflunomide and teriflunomide by native α-, β- and γ-cyclodextrins was investigated through ¹H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For α-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity. The interactions via hydrogen bonding are responsible for high negative enthalpy and entropy changes accompanying the complexation of cyclodextrins with teriflunomide. These results were in agreement with the molecular modeling calculations, which provide a clearer picture of the involved interactions at the atomic level.     

Evolution of MicroRNA Biogenesis Genes in the Sterlet (Acipenser ruthenus) and Other Polyploid Vertebrates

MicroRNAs play a crucial role in eukaryotic gene regulation. For a long time, only little was known about microRNA-based gene regulatory mechanisms in polyploid animal genomes due to difficulties of polyploid genome assembly. However, in recent years, several polyploid genomes of fish, amphibian, and even invertebrate species have been sequenced and assembled. Here we investigated several key microRNA-associated genes in the recently sequenced sterlet (Acipenser ruthenus) genome, whose lineage has undergone a whole genome duplication around 180 MYA. We show that two paralogs of drosha, dgcr8, xpo1, and xpo5 as well as most ago genes have been retained after the acipenserid-specific whole genome duplication, while ago1 and ago3 genes have lost one paralog. While most diploid vertebrates possess only a single copy of dicer1, we strikingly found four paralogs of this gene in the sterlet genome, derived from a tandem segmental duplication that occurred prior to the last whole genome duplication. ago1,3,4 and exportins1,5 look to be prone to additional segment duplications producing up to four-five paralog copies in ray-finned fishes. We demonstrate for the first time exon microsatellite amplification in the acipenserid drosha2 gene, resulting in a highly variable protein product, which may indicate sub- or neofunctionalization. Paralogous copies of most microRNA metabolism genes exhibit different expression profiles in various tissues and remain functional despite the rediploidization process. Subfunctionalization of microRNA processing gene paralogs may be beneficial for different pathways of microRNA metabolism. Genetic variability of microRNA processing genes may represent a substrate for natural selection, and, by increasing genetic plasticity, could facilitate adaptations to changing environments.     

A 2D quadrangular pyramid photoelectric autocollimator with extended angle measurement range

A photoelectric autocollimator with high accuracy and extended measurement range based on the quadrangular pyramid is proposed, and the corresponding algorithms are also deduced. A new image processing algorithm has been proposed to improve the accuracy, and the corresponding errors are also estimated, the error does not exceed half a pixel when the distance between the marks more than two radii. The experimental results have verified that the measurement range of the proposed two-dimensional (2D) quadrangular pyramid photoelectric autocollimator can be increased times than that of the flat mirror photoelectric autocollimator from 10′ to 15′. The accuracy is better than 1″ when the deflection is less than 15′.     

Decentralised decision making in heterogeneous teams using anonymous optimisation

This paper considers the scenario where multiple autonomous agents must cooperate in making decisions to minimise a continuous and differentiable team cost function. A distributed and asynchronous optimisation algorithm is presented which allows each agent to incrementally refine their decisions while intermittently communicating with the rest of the team. A convergence analysis provides quantitative requirements on the frequency agents must communicate that is prescribed by the structure of the decision problem. In general the solution method will require every agent to communicate to and have a model of every other agent in the team. To overcome this, a specific subset of systems, called Partially Separable, is defined. These systems only require each agent to have a combined summary of the rest of the team and allows each agent to communicate locally over an acyclic communication network, greatly increasing the scalability of the system.     

Genuinity Signatures: Designing Signatures for Verifying 3D Object Genuinity

3D computer graphics models and digitally-controlled manufacturing have come together to enable the design, visualization, simulation, and automated creation of complex 3D objects. In our work, we propose and implement a framework for designing computer graphics objects and digitally manufacturing them such that no adversary can make imitations or counterfeit copies of the physical object, even if the adversary has a large number of original copies of the object, knowledge of the original object design, and has manufacturing precision that is comparable to or superior to that of the legitimate creator of the object. Our approach is to design and embed a signature on the surface of the object which acts as a certificate of genuinity of the object. The signature is detectable by a signature-reading device, based on methods in computer graphics and computer vision, which contains some of the secret information that was used when marking the physical object. Further, the compromise of a signature-reading device by an adversary who is able to extract all its secrets, does not enable the adversary to create counterfeit objects that fool other readers, thereby still enabling reliable copy detection. We implemented a prototype of our scheme end-to-end, including the production of the physical object and the genuinity-testing device.     

低k集成的曙光

随着对新化学品和集成方案了解的加深，我们不但可以减轻介电层孔隙率增加引起的负担还可以降低工艺对超低k薄膜的损伤。     

Integrated energy performance modeling for a retail store building

This paper presents an integrated energy performance modeling approach that considers heat and mass transfer through building envelope, HVAC (heating, ventilation, and air conditioning) and refrigeration systems of a retail store building with limited measured data. The internal heat gains/losses were estimated based on an Extended Kalman Filter. The simulation coupling strategy among room top units (RTUs), refrigeration display cases and zones is based on the ping-pong coupling strategy. The integrated model was validated against measured data from June to August, 2011. The results show that temperature prediction is within the ±1.5°C error band and the RTU electricity energy use prediction is within the ±10% error band. The difference between measured and simulated annual electricity consumption from the refrigeration system is 3%. Based on further analysis and diagnostics, deviations of model predictions from measured data were found to be partially due to the faults in the RTUs. Such deviation accounts for a 4% saving of the total building electrical energy consumption.