Proactive Anomaly Detection in Large-Scale Cloud-Native Databases

This disclosure describes techniques to identify anomalous patterns in customer workloads from database logs and to enable timely, corrective action that ensures uninterrupted operation of the database. Examples of anomalies include sudden increases (bursts) in the number of error messages written to a log file. An adaptive behavior norm is defined for each message type. Time instances or periods when the gap between messages of a given type in the database log deviate from the expected behavior norms are detected. A deviation from the behavior norm is a potential indicator of database problems. An anomaly detection tool outputs a ranked list of log statements exhibiting spikes of activity along with their time intervals that a database administrator (DBA) can examine to take corrective action. By automating anomaly detection, the valuable time of DBAs can be spent acting on issues rather than finding them

Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for Transcriptional Interactions Related to Growth and Synaptic Plasticity

Background: Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Methodology: We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. Conclusions: The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment i

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Novel Grey Seasonal Model for Natural Gas Production Forecasting

To accurately predict the time series of energy data, an optimized Hausdorff fractional grey seasonal model was proposed based on the complex characteristics of seasonal fluctuations and local random oscillations of seasonal energy data. This paper used a new seasonal index to eliminate the seasonal variation of the data and weaken the local random fluctuations. Furthermore, the Hausdorff fractional accumulation operator was introduced into the traditional grey prediction model to improve the weight of new information, and the particle swarm optimization algorithm was used to find the nonlinear parameters of the model. In order to verify the reliability of the new model in energy forecasting, the new model was applied to two different energy types, hydropower and wind power. The experimental results indicated that the model can effectively predict quarterly time series of energy data. Based on this, we used China’s quarterly natural gas production data from 2015 to 2021 as samples to forecast those for 2022–2024. In addition, we also compared the proposed model with the traditional statistical models and the grey seasonal models. The comparison results showed that the new model had obvious advantages in predicting quarterly data of natural gas production, and the accurate prediction results can provide a reference for natural gas resource allocation

Advances in the pathogenesis of Alzheimer’s disease: a re-evaluation of amyloid cascade hypothesis

Abstract Alzheimer’s disease (AD) is a common neurodegenerative disease characterized clinically by progressive deterioration of memory, and pathologically by histopathological changes including extracellular deposits of amyloid-beta (A-beta) peptides forming senile plaques (SP) and the intracellular neurofibrillary tangles (NFT) of hyperphosphorylated tau in the brain. This review focused on the new developments of amyloid cascade hypothesis with details on the production, metabolism and clearance of A-beta, and the key roles of some important A-beta-related genes in the pathological processes of AD. The most recent research advances in genetics, neuropathology and pathogenesis of the disease were also discussed.</p

Identification of a Small Molecule that Binds to the PD-L1 Dimer Interface

In recent years, antibody drugs targeting PD-1/PD-L1 immune checkpoints have shown immense clinical benefits in cancer treatment. However, these drugs suffer from poor patient tolerance, large and difficult-to-control adverse reactions, insufficient oral bioavailability, and low response rates for most solid tumours, which hinder their further application. Due to the poor pharmacodynamic properties and the shallow interface of the PD-1/PD-L1 binding pocket, progress in developing small molecule PD-1/PD-L1 inhibitors that can overcome the limitations of monoclonal antibodies has been slow. Recently, many compounds have been discovered that bind to the PD-L1/PD-L1 dimer interface, providing a promising avenue for inhibiting the interaction of PD-1/PD-L1 with small molecules. Among them, biphenyl compounds that induce PD-L1 dimerization and block the interaction of PD-1 and PD-L1 have shown strong activity. In this study, we conducted virtual screening against the PD-L1 dimer interface and identified a novel biphenyl small molecule inhibitor, ZQ-4, with a unique structure. Molecular dynamics simulations were used to determine the possible binding conformations of ZQ-4 and PD-L1 dimer, and the Alanine Scanning-Interaction Entropy method was used to compare the binding free energy of ZQ-4 and BMS-200. These results provide a foundation for optimizing the hit compound and exploring novel PD-1/PD-L1 small molecule inhibitors