Multidimensional Phylogenetic Metrics Identify Class I Aminoacyl-tRNA Synthetase Evolutionary Mosaicity and Inter-Modular Coupling

The role of aminoacyl-tRNA synthetases (aaRS) in the emergence and evolution of genetic coding poses challenging questions concerning their provenance. We seek evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—mutation frequency, its uniformity, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from successive genetic sources. Metrics for different modules vary in accordance with their presumed functionality. Sequences derived from the ATP– and amino acid– binding sites exhibit specific two-way coupling to those derived from Connecting Peptide 1, a third module whose metrics suggest later acquisition. The data help validate: (i) experimental fragmentations of the canonical Class I structure into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that the ancestral Class I aaRS gene also encoded a Class II ancestor in frame on the opposite strand. A 46-residue Class I “protozyme” roots the Class I tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting implies near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.     

包容性工程—借助工程技术发明为身体或精神障碍人士赋能

1. Background The use of engineering tools, design, research, and thinking to create environments and capabilities whereby individuals who are currently under-e...     

The performance of a distributed combat simulation with the time warp operating system

This paper analyzes the performance of a discrete-event combat simulation executed on a parallel processor under control of the Time Warp Operating System. Time Warp is in a class of distributed simulation methods called Optimistic methods which have proven to be useful over a wide range of simulations. The combat simulation used for this performance study, called STB88, is a division-corps model incorporating a number of different types of computations. The speed-up for three versions of this model on the Caltech/JPL Mark III Hypercube and the BBN Butterfly parallel processors was measured relative to an efficient sequential execution of the same model on the same hardware. The results indicate that STB88 version 1 achieves a speed-up of 28.6 on 60 Mark III processors, while STB88 version 2 achieves a speed-up of 36.8 on 100 Butterfly processors. Version 3 of STB88 achieved a speed-up of 38.5 on 128 Mark III processors. The versions differed only in their interface to Time Warp. On the Butterfly, the sequential execution completed in 2 hours, while the 100 processor execution completed in 3.2 minutes.     

A taxonomic-based joint species distribution model for presence-only data

Species distribution models (SDMs) are an important class of model for mapping taxa spatially and are a key tool for tackling biodiversity loss. However, most common SDMs depend on presence–absence data and, despite the accumulation and exponential growth of biological occurrence data across the globe, the available data are predominantly presence-only (i.e. they lack real absences). Although presence-only SDMs do exist, they inevitably require assumptions about absences of the considered taxa and they are specified mostly for single species and, thus, do not exploit fully the information in related taxa. This greatly limits the utility of global biodiversity databases such as GBIF. Here, we present a Bayesian-based SDM for multiple species that operates directly on presence-only data by exploiting the joint distribution between the multiple ecological processes and, crucially, identifies the sampling effort per taxa which allows inference on absences. The model was applied to two case studies. One, focusing on taxonomically diverse taxa over central Mexico and another focusing on the monophyletic family Cactacea over continental Mexico. In both cases, the model was able to identify the ecological and sampling effort processes for each taxon using only the presence observations, environmental and anthropological data.     

The current perspective of the PA 1957 gas well pillar study and its implications for longwall gas well pillars

Many states rely upon the Pennsylvania 1957 Gas Well Pillar Study to evaluate the coal barrier surrounding gas wells. The study included 77 gas well failure cases that occurred in the Pittsburgh and Freeport coal seams over a 25-year span. At the time, coal was mined using the room-and-pillar mining method with full or partial pillar recovery, and square or rectangle pillars surrounding the gas wells were left to protect the wells. The study provided guidelines for pillar sizes under different overburden depths up to213 m(700 ft). The 1957 study has also been used to determine gas well pillar sizes in longwall mines since longwall mining began in the 1970 s. The original study was developed for room-and-pillar mining and could be applied to gas wells in longwall chain pillars under shallow cover. However, under deep cover, severe deformations in gas wells have occurred in longwall chain pillars. Presently, with a better understanding of coal pillar mechanics, new insight into subsidence movements induced by retreat mining, and advances in numerical modeling, it has become both critically important and feasible to evaluate the adequacy of the 1957 study for longwall gas well pillars. In this paper, the data from the 1957 study is analyzed from a new perspective by considering various factors, including overburden depth, failure location, failure time, pillar safety factor(SF), and floor pressure. The pillar SF and floor pressure are calculated by considering abutment pressure induced by full pillar recovery. A statistical analysis is performed to find correlations between various factors and helps identify the most significant factors for the stability of gas wells influenced by retreat mining. Through analyzing the data from the 1957 study, the guidelines for gas well pillars in the 1957 study are evaluated for their adequacy for roomand-pillar mining and their applicability to longwall mining. Numerical modeling is used to model the stability of gas wells by quantifying the mining-induced stresses in gas well casings. Results of this study indicate that the guidelines in the 1957 study may be appropriate for pillars protecting conventional gas wells in both room-and-pillar mining and longwall mining under overburden depths up to 213 m(700 ft),but may not be sufficient for protective pillars under deep cover. The current evaluation of the 1957 study provides not only insights about potential gas well failures caused by retreat mining but also implications for what critical considerations should be taken into account to protect gas wells in longwall mining.     

Effect of phase maldistribution on performance of two-phase catalytic monolith reactor and its comparison with trickle bed reactor

Monolith reactors are widely considered as an alternative to the conventional trickle bed reactor. For the commercial deployment of monolith reactors, comparative performance studies are required. Reliable comparative and performance studies require a detailed understanding of the effect of phase distribution/maldistribution on the performance studies. In this work, performance and comparative studies were carried out in a relatively large column that was 4.8 cm in diameter. Experiments were performed in the same conditions that were used in studies for which phase distribution data were available. Since the properties of the catalyst used were different in both the reactors, the apparent kinetics were studied to facilitate the comparison. The hydrogenation of alpha-methyl styrene (AMS) was used as a test reaction. From the performance studies, it was found that the effect of maldistribution on the performance was stronger than the catalyst availability. From the comparative studies, it was found that the monolith reactor with maldistributed flow conditions provides higher productivity than the trickle bed reactor.     

Klärschlammverbrennung in einer stationären Wirbelschicht mit integrierter Phosphor-Rückgewinnung

Currently, wet-chemical and thermochemical processes in particular are being discussed for the future obligatory recovery of phosphorus from sewage sludge. The coupling of phosphorus recovery with incineration in stationary fluidized bed incinerators, the dominant mono-incineration technology, offers potential advantages in terms of aftertreatment costs and economic efficiency. Tests have shown that by adjusting the incineration conditions and adding additives, an ash could be produced that corresponds to the fertilizer ordinance (DüMV) and can, therefore, potentially be used as phosphorus recyclate.     

PET Recycling – Contributions of Crystallization to Sustainability

Polyethylene terephthalate (PET) is one of the most common thermoplastic polymers and its durability has become a major environmental concern. The current public debate on plastic debris also triggered the revision of PET recycling technologies. This Research Article focuses on the chemical recycling of PET by means of methanolysis. The process degrades PET into two main reaction products, dimethyl terephthalate (DMT) and ethylene glycol (EG). Subsequent separation by distillation combined with crystallization removes critical impurities and non-PET components from co-polymers, providing monomers of high purity needed for re-polymerization purposes.     

Mechanisms of EGFR Resistance in Glioblastoma

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite numerous efforts to target epidermal growth factor receptor (EGFR), commonly dysregulated in GBM, approaches directed against EGFR have not achieved the same degree of success as seen in other tumor types, particularly as compared to non-small cell lung cancer (NSCLC). EGFR alterations in glioblastoma lie primarily in the extracellular domain, unlike the kinase domain alterations seen in NSCLC. Small molecule inhibitors are difficult to develop for the extracellular domain. Monoclonal antibodies can be developed to target the extracellular domain but must contend with the blood brain barrier (BBB). We review the role of EGFR in GBM, the history of trialed treatments, and the potential paths forward to target the pathway that may have greater success.     

Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

Ru^II-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new Ru^II-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes ( 2 a , b and 5 ) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC₅₀=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.