AlphaFold-Predicted Structures of KCTD Proteins Unravel Previously Undetected Relationships among the Members of the Family

One of the most striking features of KCTD proteins is their involvement in apparently unrelated yet fundamental physio-pathological processes. Unfortunately, comprehensive structure–function relationships for this protein family have been hampered by the scarcity of the structural data available. This scenario is rapidly changing due to the release of the protein three-dimensional models predicted by AlphaFold (AF). Here, we exploited the structural information contained in the AF database to gain insights into the relationships among the members of the KCTD family with the aim of facilitating the definition of the structural and molecular basis of key roles that these proteins play in many biological processes. The most important finding that emerged from this investigation is the discovery that, in addition to the BTB domain, the vast majority of these proteins also share a structurally similar domain in the C-terminal region despite the absence of general sequence similarities detectable in this region. Using this domain as reference, we generated a novel and comprehensive structure-based pseudo-phylogenetic tree that unraveled previously undetected similarities among the protein family. In particular, we generated a new clustering of the KCTD proteins that will represent a solid ground for interpreting their many functions.

A COMPARISON OF PROJECT PLANNING AND SCHEDULING SOFTWARE’S PRIMAVERA AND MICROSOFT PROJECT USED IN THE CONSTRUCTION INDUSTRY

Planning and scheduling is extremely important role in construction projects thank to the increasing difficulties during this field. Construction Planning is that the necessary warning to Scheduling and determining general sequence, defining labour tasks, construction methods and assigning responsibilities, inappropriate planning can cause major delays with the project work. For the planning and scheduling work requires huge amount of paperwork, which makes the management very burdensome. These problems may be solved employing a project management software which helps to grant a planned approach to planning. Nowadays use of project management (PM) software as a tool for managing and organizing work has gained its importance in construction industry and continues to grow at a faster pace in other industries also. During this study, attempt is made to check project management software such as MS project and Primavera and their feasibility is studied.

14 Diaphragmatic Electrical Activity in Preterm Infants on Non-Invasive High Frequency Oscillatory Ventilation (DEAP-NHFO Study)

Primary Subject area Neonatal-Perinatal Medicine Background Continuous Positive Airway Pressure (CPAP) is a common form of non-invasive respiratory support for preterm infants. Non-invasive high frequency ventilation (NHFOV) is a relatively new method of non-invasive respiratory support. NHFOV is being increasingly utilized in clinical practice in an attempt to prevent intubation and minimize ventilator-induced lung injury in preterm infants. Preliminary studies suggest superiority of NHFOV over CPAP, but little is known about its mechanism of action and its effect on respiratory control in the newborn. We hypothesize that NHFOV reduces respiratory drive and improves ventilation, resulting in decreased patient diaphragm energy expenditure, which can be assessed by measuring the electrical activity of the diaphragm (Edi). Objectives The objective of this study is to compare the effects of non-invasive respiratory support delivered by nasal CPAP versus NHFOV on respiratory pattern, as assessed by the Edi in very low birth weight (VLBW) preterm infants. Design/Methods In a prospective, randomized, crossover study, 20 preterm infants with birth weights ≤1500 g requiring CPAP were randomized to either NHFOV or CPAP for 105 min, followed by crossover to the other method for the same duration. Edi was continuously measured by a feeding catheter with miniaturized sensors embedded in its wall (Maquet, Solna). The general sequence was 15 minutes for acclimation to the mode, 75 minutes for a feed to be completed, followed by 15 minutes for breath-by-breath analyses of neural breathing pattern. Primary outcome was difference in the peak Edi between CPAP and NHFOV. Secondary outcomes included difference in other measures of respiratory drive: neural respiratory rate, neural inspiratory time, diaphragm energy expenditure, transcutaneous pCO2, number of apnea episodes on the Edi, and episodes of clinically significant apnea. Results No significant differences in Edi timing, Edi min, Edi peak, apnea, or CO2 were observed between the two modes of respiratory support. Conclusion In this cohort of VLBW preterm infants, neural respiratory pattern was not significantly different between NHFOV and CPAP. With this baseline information in stable preterm infants, it would now be important to assess whether these results hold true in infants with more severe lung disease, where NHFOV is often used as escalating support from CPAP.

ECNet is an evolutionary context-integrated deep learning framework for protein engineering

Machine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 β-lactamase and identified variants with improved ampicillin resistance with high success rates.

Evolution of the Reaction and Alteration of Mudstone with Ordinary Portland Cement Leachates: Sequential Flow Experiments and Reactive-Transport Modelling

The construction of a repository for geological disposal of radioactive waste will include the use of cement-based materials. Following closure, groundwater will saturate the repository and the extensive use of cement will result in the development of a highly alkaline porewater, pH > 12.5; this fluid will migrate into and react with the host rock. The chemistry of the fluid will evolve over time, initially high [Na] and [K], evolving to a Ca-rich fluid, and finally returning to the groundwater composition. This evolving chemistry will affect the long-term performance of the repository, altering the physical and chemical properties, including radionuclide behaviour. Understanding these changes forms the basis for predicting the long-term evolution of the repository. This study focused on the determination of the nature and extent of the chemical reaction, as well as the formation and persistence of secondary mineral phases within a mudstone, comparing data from sequential flow experiments with the results of reactive transport modelling. The reaction of the mudstone with the cement leachates resulted in small changes in pH with the precipitation of calcium aluminium silicate hydrate (C-(A-)S-H) phases of varying compositions. As the system evolves, secondary C-(A-)S-H phases re-dissolve and are replaced by secondary carbonates. This general sequence was successfully simulated using reactive transport modelling.

Paraspinal Muscle Activity Differences in Various Subtypes of Idiopathic Scoliosis

Background: Scoliosis refers to deviation of spinal alignment in three dimensional planes. In response to functional demands Muscle fibers change in motor unit function. Knowledge of difference in muscle fiber activity in functional situations allows us to plan curve specific effective physical therapy. Methodology: All study subjects were categorised based on Rigo Classification and assessed for para spinal muscle activity by Surface Electro Myography at cervical, thoracic, lumbar, concave- convex sides of apex and lumbar /lumbo sacral regions of spine in general sequence and curve specific sequence. Results: Total number of subjects were 25 (16 female and 9 male). Age ranging from 12 to 39 years and Risser from 1-5. Overall maximum amplitudes recorded in antigravity positions. Amplitudes of as low as (M±σ = mean± standard deviation) M±σ: 0.92±0.79µv to M± σ: 1411.6±734.9µv were found. Conclusion: Differences in right and left paraspinal activity was observed in general and specific sequences, but this difference was not consistent in general and specific sequence surface electro myography. Maximum amplitudes found at lumbar and lumbo sacral regions on antigravity positions than other positions. Convex side has more activity than concave sides at apex regions. Differences were not similar in all positions, this difference in left and right side was varying with curve type and type of movement. Results of paraspinal activity may be used for planning of suitable exercises after achieving best possible correction in sagittal and frontal planes. Key words: Paraspinal muscle activity differences, idiopathic scoliosis, deviation of spinal alignment.

Present structure of the Near-Bug area: conditions of formation and history of development

General sequence establishment of geological Precambrian events and associating formations, which were created in them, to the results of isotope age definition, is the task, which has no single valued solution for southwestern part of the Ukrainian Shield. Important is to create a general development model, which will describe the modern geological structure of an area, structural and textural rocks features, accounting PT-conditions in the Earth's crust during the Archean—Paleoproterozoic. Isotopic age determination demonstrates, that from the moment of protolith creation (not later than 3.75 billion years ago, up to 1.9 billion years ago), intrusion of mantle melts and partial melting of the lower crustal rocks, occurred many times over. Pobuzhie formation cannot be imagined, as a single process of accumulation, plunge, crumpling into folds and sedimentary strata metamorphism. It is necessary, to take into account, the plume (mantle) component of the general geodynamic process. In the structure of the Bug megablock and Golovanevskaya suture zone, two main structural plans are displayed. The main part of the territory displays a region of areal distribution of Archean enderbites (generated 2.8 billion years ago) and Proterozoic granites (generated 2.03 billion years ago). The paper compares the temperature distribution with depth, corresponding to the thermal model of the metamorphic temperatures found in the samples, and the solidus temperatures of the basic rocks. It is shown that at the time of the metamorphism development, 2.0 billion years ago, the rocks were at a depth of more than 20 km, and before that — at an even greater depth. During the Archean and Paleoproterozoic, the center of partial melting was repeatedly renewed here, since the temperatures were higher than the solidus temperature of gabbro. Metamorphic changes (and more often migmatization, partial melting and following crystallization in the granulite facies conditions) happened after the presence of the thermal asthenosphere on the core—mantle border, and were accompanied by bringing the substance from it. Therefore the main part of modern surface is folded by palingenic granites. In Archean and Paleoproterozoic the composition of substances were different. After 2.0 billion years ago the level of modern surface was located higher. The second structural plan is presented with vertical structures, building of which often close to concentrically zonal or linear monoclinal. They are confined to fault zones and nodes of their intersections. These structures contain rock complexes, which did not occur until 2.0 billion years ago on any craton in the world.

Functional characterization of splicing regulatory elements

Background: RNA binding protein-RNA interactions mediate a variety of processes including pre-mRNA splicing, translation, decay, polyadenylation and many others. Previous high-throughput studies have characterized general sequence features associated with increased and decreased splicing of certain exons, but these studies are limited by not knowing the mechanisms, and in particular, the mediating RNA binding proteins, underlying these associations. Results: Here we utilize ENCODE data from diverse data modalities to identify functional splicing regulatory elements and their associated RNA binding proteins. We identify features which make splicing events more sensitive to depletion of RNA binding proteins, as well as which RNA binding proteins act as splicing regulators sensitive to depletion. To analyze the sequence determinants underlying RBP-RNA interactions impacting splicing, we assay tens of thousands of sequence variants in a high-throughput splicing reporter called Vex-seq and confirm a small subset in their endogenous loci using CRISPR base editors. Finally, we leverage other large transcriptomic datasets to confirm the importance of RNA binding proteins which we designed experiments around and identify additional RBPs which may act as additional splicing regulators of the exons studied. Conclusions: This study identifies sequence and other features underlying splicing regulation mediated specific RNA binding proteins, as well as validates and identifies other potentially important regulators of splicing in other large transcriptomic datasets.

A Note on the Asymptotic Behavior of the Distribution Function of a General Sequence

The aim of this note is to study the distribution function of certain sequences of positive integers, including, for example, Bell numbers, factorials and primorials. In fact, we establish some general asymptotic formulas in this regard. We also prove some limits that connect these sequences with the number e. Furthermore, we present a generalization of the primorial.

Predicting Long non-coding RNAs through feature ensemble learning

Background Many transcripts have been generated due to the development of sequencing technologies, and lncRNA is an important type of transcript. Predicting lncRNAs from transcripts is a challenging and important task. Traditional experimental lncRNA prediction methods are time-consuming and labor-intensive. Efficient computational methods for lncRNA prediction are in demand. Results In this paper, we propose two lncRNA prediction methods based on feature ensemble learning strategies named LncPred-IEL and LncPred-ANEL. Specifically, we encode sequences into six different types of features including transcript-specified features and general sequence-derived features. Then we consider two feature ensemble strategies to utilize and integrate the information in different feature types, the iterative ensemble learning (IEL) and the attention network ensemble learning (ANEL). IEL employs a supervised iterative way to ensemble base predictors built on six different types of features. ANEL introduces an attention mechanism-based deep learning model to ensemble features by adaptively learning the weight of individual feature types. Experiments demonstrate that both LncPred-IEL and LncPred-ANEL can effectively separate lncRNAs and other transcripts in feature space. Moreover, comparison experiments demonstrate that LncPred-IEL and LncPred-ANEL outperform several state-of-the-art methods when evaluated by 5-fold cross-validation. Both methods have good performances in cross-species lncRNA prediction. Conclusions LncPred-IEL and LncPred-ANEL are promising lncRNA prediction tools that can effectively utilize and integrate the information in different types of features.