Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator

At the molecular level, members of the NKx2.2 family of transcription factors establish neural compartment boundaries by repressing the expression of homeobox genes specific for adjacent domains [Muhr et al. (2001) Cell, 104, 861–873; Weiss et al. (1998) Genes Dev., 12, 3591–3602]. The Drosophila homologue, vnd, interacts genetically with the high-mobility group protein, Dichaete, in a manner suggesting co-operative activation [Zhao and Skeath (2002) Development, 129, 1165–1174]. However, evidence for direct interactions and transcriptional activation is lacking. Here, we present molecular evidence for the interaction of Vnd and Dichaete that leads to the activation of target gene expression. Two-hybrid interaction assays indicate that Dichaete binds the Vnd homeodomain, and additional Vnd sequences stabilize this interaction. In addition, Vnd has two activation domains that are typically masked in the intact protein. Whether vnd can activate or repress transcription is context-dependent. Full-length Vnd, when expressed as a Gal4 fusion protein, acts as a repressor containing multiple repression domains. A divergent domain in the N-terminus, not found in vertebrate Vnd-like proteins, causes the strongest repression. The co-repressor, Groucho, enhances Vnd repression, and these two proteins physically interact. The data presented indicate that the activation and repression domains of Vnd are complex, and whether Vnd functions as a transcriptional repressor or activator depends on both intra- and inter-molecular interactions

Combined Metformin and Resveratrol Confers Protection Against UVC-Induced DNA Damage in A549 Lung Cancer Cells via Modulation of Cell Cycle Checkpoints and DNA Repair

Aging in humans is a multi-factorial cellular process that is associated with an increase in the risk of numerous diseases including diabetes, coronary heart disease and cancer. Aging is linked to DNA damage, and a persistent source of DNA damage is exposure to ultraviolet (UV) radiation. As such, identifying agents that confer protection against DNA damage is an approach that could reduce the public health burden of age-related disorders. Metformin and resveratrol have both shown effectiveness in preventing several age-related diseases; using human A549 cells, we investigated whether metformin or resveratrol, alone or combined, prevent UVC-induced DNA damage. We found that metformin inhibited UVC-induced upregulation of p53, as well as downregulated the expression of two DNA damage markers: γH2AX and p-chk2. Metformin also upregulated DNA repair as evidenced by the increase in expression of p53R2. Treatment with metformin also induced cell cycle arrest in UVC-induced cells, in correlation with a reduction in the levels of cyclin E/cdk2/Rb and cyclin B1/cdk1. Compared to metformin, resveratrol as a single agent showed less effectiveness in counteracting UVC-elicited cellular responses. However, resveratrol displayed synergism when combined with metformin as shown by the downregulation of p53/γH2AX/p-chk2. In conclusion, the results of the present study validate the effectiveness of metformin, alone or with the addition of resveratrol, in reducing the risk of aging by conferring protection against UV-induced DNA damage

Usability and Usefulness of Circularity Indicators for Manufacturing Performance Management

Advances in industrial digitalization present many opportunities for process and product data exploitation in manufacturing, unlocking new systemic measures of performance beyond a single machine, process, facility area and even beyond the factory gates. However, existing data models and manufacturing systems\u27 performance measures are still focused on productivity, quality and delivery time, which could potentially lead to an accelerated linear economy. To shift to more circular industrial systems, we need to identify and assess circularity opportunities in ways that align the goals of sustainable and industrial development. In this study, micro-level circular indicators were reviewed, selected, analysed and tested in a manufacturing company to evaluate their usability and usefulness to guide process improvements. The aim is to enable circular and eco-efficient solutions towards sustainable production systems. Usability and usefulness of the indicators are essential to their integration into established environmental and operations management systems. The main contribution of this study is in the identification of key features making circularity indicators usable and useful from a manufacturer\u27s perspective. The conclusion also suggests directions for further research on tools and methods to support circular manufacturing

Data production models for the CDF experiment

The data production for the CDF experiment is conducted on a large Linux PC farm designed to meet the needs of data collection at a maximum rate of 40 MByte/sec. We present two data production models that exploits advances in computing and communication technology. The first production farm is a centralized system that has achieved a stable data processing rate of approximately 2 TByte per day. The recently upgraded farm is migrated to the SAM (Sequential Access to data via Metadata) data handling system. The software and hardware of the CDF production farms has been successful in providing large computing and data throughput capacity to the experiment.Comment: 8 pages, 9 figures; presented at HPC Asia2005, Beijing, China, Nov 30 - Dec 3, 200

Data processing model for the CDF experiment

The data processing model for the CDF experiment is described. Data processing reconstructs events from parallel data streams taken with different combinations of physics event triggers and further splits the events into datasets of specialized physics datasets. The design of the processing control system faces strict requirements on bookkeeping records, which trace the status of data files and event contents during processing and storage. The computing architecture was updated to meet the mass data flow of the Run II data collection, recently upgraded to a maximum rate of 40 MByte/sec. The data processing facility consists of a large cluster of Linux computers with data movement managed by the CDF data handling system to a multi-petaByte Enstore tape library. The latest processing cycle has achieved a stable speed of 35 MByte/sec (3 TByte/day). It can be readily scaled by increasing CPU and data-handling capacity as required.Comment: 12 pages, 10 figures, submitted to IEEE-TN

Sensory Processing and Community Participation in Autistic Adults

Background Sensory processing differences have been shown to impact involvement in community activities. However, relatively little is known about how these differences affect community participation in autistic adults. Objective The objective of this study was to explore how sensory processing patterns of autistic adults impact community participation, including where people go, what they do, the amount of time in the community, and preferred locations. Methods We used data gathered from six autistic adults and their caregivers who participated in two studies. From Study 1, we reviewed results of the Adolescent and Adult Sensory Profile (AASP) and transcripts from interviews with caregivers. From Study 2, we reviewed GPS tracking data and transcripts from structured interviews with autistic adults focused on community participation. We read transcript data, identified quotes related to sensory processing and community participation and constructed individual participant narratives which linked findings from interviews, AASP, and GPS tracking. Results Participants included three males and three females ranging in age from 29 to 51. Each participant had a unique sensory processing profile that influenced where they went, the activities in which they engaged, how much time they spent in the community, and their preferred locations. Those whose sensory processing patterns indicated sensory sensitivity and sensory avoiding described the experience of certain environments as overwhelming and fatiguing and thus spent less time in the community and visited fewer places than those with other sensory processing patterns. Conclusion Results highlight the importance of sensory processing, especially as it impacts participation in the community. Sensory processing patterns should be considered along with other personal and contextual factors when assessing community participation and personal sensory processing patterns should be matched with activities and environmental demands

Hierarchical colour image segmentation by leveraging RGB channels independently

In this paper, we introduce a hierarchical colour image segmentation based on cuboid partitioning using simple statistical features of the pixel intensities in the RGB channels. Estimating the difference between any two colours is a challenging task. As most of the colour models are not perceptually uniform, investigation of an alternative strategy is highly demanding. To address this issue, for our proposed technique, we present a new concept for colour distance measure based on the inconsistency of pixel intensities of an image which is more compliant to human perception. Constructing a reliable set of superpixels from an image is fundamental for further merging. As cuboid partitioning is a superior candidate to produce superpixels, we use the agglomerative merging to yield the final segmentation results exploiting the outcome of our proposed cuboid partitioning. The proposed cuboid segmentation based algorithm significantly outperforms not only the quadtree-based segmentation but also existing state-of-the-art segmentation algorithms in terms of quality of segmentation for the benchmark datasets used in image segmentation. © 2019, Springer Nature Switzerland AG