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Methyl-CpG binding domain protein sequencing (MBD-seq) is widely used to survey DNA methylation patterns. However, the optimal experimental parameters for MBD-seq remain unclear and the data analysis remains challenging. In this study, we generated high depth MBD-seq data in MCF-7 cell and developed a bi-asymmetric-Laplace model (BALM) to perform data analysis. We found that optimal efficiency of MBD-seq experiments was achieved by sequencing ∼100 million unique mapped tags from a combination of 500 mM and 1000 mM salt concentration elution in MCF-7 cells. Clonal bisulfite sequencing results showed that the methylation status of each CpG dinucleotides in the tested regions was accurately detected with high resolution using the proposed model. These results demonstrated the combination of MBD-seq and BALM could serve as a useful tool to investigate DNA methylome due to its low cost, high specificity, efficiency and resolution.

Abstract Background: Acute Lymphoblastic Leukaemia (ALL) is the most common cancer in children. Over the past four decades, research has advanced the treatment of this cancer from a less than 60% chance of survival to over 85% today. The causal molecular mechanisms remain unclear. Here, we performed sequencing-based genomic DNA methylation profiling of eight paediatric ALL patients using archived bone marrow smear microscope slides. Findings: SOLiD™ sequencing data was collected from Methyl-Binding Domain (MBD) enriched fractions of genomic DNA. The primary tumour and remission bone marrow sample was analysed from eight patients. Four patients relapsed and the relapsed tumour was analysed. Input and MBD-enriched DNA from each sample was sequenced, aligned to the hg19 reference genome and analysed for enrichment peaks using MACS (Model-based Analysis for ChIP-Seq) and HOMER (Hypergeometric Optimization of Motif EnRichment). In total, 3.67 gigabases (Gb) were sequenced, 2.74 Gb were aligned to the reference genome (average 74.66% alignment efficiency). This dataset enables the interrogation of differential DNA methylation associated with paediatric ALL. Preliminary results reveal concordant regions of enrichment indicative of a DNA methylation signature. Conclusion: Our dataset represents one of the first SOLiD™MBD-Seq studies performed on paediatric ALL and is the first to utilise archival bone marrow smears. Differential DNA methylation between cancer and equivalent disease-free tissue can be identified and correlated with existing and published genomic studies. Given the rarity of paediatric haematopoietic malignancies, relative to adult counterparts, our demonstration of the utility of archived bone marrow smear samples to high-throughput methylation sequencing approaches offers tremendous potential to explore the role of DNA methylation in the aetiology of cancer.

Correlation analysis is one of the most prolific statistical methods used in data analysis problems, mining of knowledge focused on relationships of attributes in large datasets, and in various predictive tasks utilizing statistical, machine learning, and deep learning models. This approach to the analysis of functional relationships in multidimensional datasets is commonly used in conjunction with visual analysis approaches, which offer novel context for the relationships in data and clarify the results presented in large correlation matrices. One of such visualization methods uses graphical models called correlation graphs and chains, which visualize individual direct and indirect relationships between pairs of attributes in a dataset of interest as a graph structure, where vertices of the graph represent attributes of the dataset and edges between vertices represent the correlation of these attributes. This work focuses on the definition, identification, and exploration of so-called correlation cycles, which can be—through their deconstruction—used as an approach to lower error values in regression tasks. After the implementation of the correlation cycle identification and deconstruction, the proposed concept is evaluated on predictive analysis tasks in the context of three benchmarking datasets from the engineering field—the Sensor dataset, Superconductivity dataset, and Energy Farm dataset. The results obtained in this study show that when using simple, explainable regressors, the method utilizing deconstructed correlation cycles reaches a lower error rate in 83.3% of regression cases compared to the same regression models without the cycle incorporation.

DNA double-strand breaks (DSB) are considered to be a severe form of DNA damage, because if left unrepaired, they can cause a cell death and, if misrepaired, they can lead to genomic instability and, ultimately, the development of cancer in multicellular organisms. The budding yeast Saccharomyces cerevisiae repairs DSB primarily by homologous recombination (HR), despite the presence of the KU70, KU80, DNA ligase IV and XRCC4 homologues, essential factors of the mammalian non-homologous end-joining (NHEJ) machinery. S. cerevisiae, however, lacks clear DNA-PKcs and ARTEMIS homologues, two important additional components of mammalian NHEJ. On the other hand, S. cerevisiae is endowed with a regulatory NHEJ component, Nej1, which has not yet been found in other organisms. Furthermore, there is evidence in budding yeast for a requirement for the Mre11/Rad50/Xrs2 complex for NHEJ, which does not appear to be the case either in Schizosaccharomyces pombe or in mammals. Here, we comprehensively describe the functions of all the S. cerevisiae NHEJ components identified so far and present current knowledge about the NHEJ process in this organism. In addition, this review depicts S. cerevisiae as a powerful model system for investigating the utilization of either NHEJ or HR in DSB repair.

As progressive managerial styles, the techniques based on \"lean thinking\" are being increasingly promoted. They are focused on applying lean production concepts to all phases of product lifecycle and also to business environment. This innovative approach strives to eliminate any wasting of resources and shortens the time to respond to customer requirements, including redesigning the structure of the organization’ supply chain. A lean organization is created mainly by employees, their creative potential, knowledge, self-realization and motivation for continuous improvement of the processes and the production systems. A set of tools, techniques and methods of lean production is basically always very similar. Only a form of their presentation or classification into individual phases of the product lifecycle may differ. The authors present the results of their research from the designing phases of production systems to optimize their dispositional solution with software support and 3D simulation and visualization. Modelling is based on use of Tecnomatix's and Photomodeler's progressive software tools and a dynamic model for capacitive dimensioning of more intelligent production systems.

We present the detector performance and early science results from GRBAlpha, a 1U CubeSat mission, which is a technological pathfinder to a future constellation of nanosatellites monitoring gamma-ray bursts (GRBs). GRBAlpha was launched in March 2021 and operates on a 550 km altitude sun-synchronous orbit. The gamma-ray burst detector onboard GRBAlpha consists of a 75x75x5 mm CsI(Tl) scintillator, read out by a dual-channel multi-pixel photon counter (MPPC) setup. It is sensitive in the ~30-900 keV range. The main goal of GRBAlpha is the in-orbit demonstration of the detector concept, verification of the detector's lifetime, and measurement of the background level on low-Earth orbit, including regions inside the outer Van Allen radiation belt and in the South Atlantic Anomaly. GRBAlpha has already detected five, both long and short, GRBs and two bursts were detected within a time-span of only 8 hours, proving that nanosatellites can be used for routine detection of gamma-ray transients. For one GRB, we were able to obtain a high resolution spectrum and compare it with measurements from the Swift satellite. We find that, due to the variable background, the time fraction of about 67 % of the low-Earth polar orbit is suitable for gamma-ray burst detection. One year after launch, the detector performance is good and the degradation of the MPPC photon counters remains at an acceptable level. The same detector system, but double in size, was launched in January 2022 on VZLUSAT-2 (3U CubeSat). It performs well and already detected three GRBs and two solar flares. Here, we present early results from this mission as well.

It is well known that silicon photomultipliers (SiPMs) are prone to radiation damage. With the increasing popularity of SiPMs among new spaceborne missions, especially on CubeSats, it is of paramount importance to characterize their performance in space environment. In this work, we report the in-orbit ageing of SiPM arrays, so-called multi-pixel photon counters (MPPCs), using measurements acquired by the GRBAlpha and VZLUSAT-2 CubeSats at low Earth orbit (LEO) spanning over three years, which in duration is unique. GRBAlpha is a 1U CubeSat launched on March 22, 2021, to a 550 km altitude sun-synchronous polar orbit (SSO) carrying on board a gamma-ray detector based on CsI(Tl) scintillator readout by eight MPPCs and regularly detecting gamma-ray transients such as gamma-ray bursts and solar flares in the energy range of ~30-900 keV. VZLUSAT-2 is a 3U CubeSat launched on January 13, 2022 also to a 550 km altitude SSO carrying on board, among other payloads, two gamma-ray detectors similar to the one on GRBAlpha. We have flight-proven the Hamamatsu MPPCs S13360-3050 PE and demonstrated that MPPCs, shielded by 2.5 mm of PbSb alloy, can be used in an LEO environment on a scientific mission lasting beyond three years. This manifests the potential of MPPCs being employed in future satellites.

GRBAlpha is a 1U CubeSat launched in March 2021 to a sun-synchronous LEO at an altitude of 550 km to perform an in-orbit demonstration of a novel gamma-ray burst detector developed for CubeSats. VZLUSAT-2 followed ten months later in a similar orbit carrying as a secondary payload a pair of identical detectors as used on the first mission. These instruments detecting gamma-rays in the range of 30-900 keV consist of a 56 cm2 5 mm thin CsI(Tl) scintillator read-out by a row of multi-pixel photon counters (MPPC or SiPM). The scientific motivation is to detect gamma-ray bursts and other HE transient events and serve as a pathfinder for a larger constellation of nanosatellites that could localize these events via triangulation. At the beginning of July 2024, GRBAlpha detected 140 such transients, while VZLUSAT-2 had 83 positive detections, confirmed by larger GRB missions. Almost a hundred of them are identified as gamma-ray bursts, including extremely bright GRB 221009A and GRB 230307A, detected by both satellites. We were able to characterize the degradation of SiPMs in polar orbit and optimize the duty cycle of the detector system also by using SatNOGS radio network for downlink.