Block2: a comprehensive open source framework to develop and apply state-of-the-art DMRG algorithms in electronic structure and beyond

Block2 is an open source framework to implement and perform density matrix renormalization group and matrix product state algorithms. Out-of-the-box it supports the eigenstate, time-dependent, response, and finite-temperature algorithms. In addition, it carries special optimizations for ab initio electronic structure Hamiltonians and implements many quantum chemistry extensions to the density matrix renormalization group, such as dynamical correlation theories. The code is designed with an emphasis on flexibility, extensibility, and efficiency, and to support integration with external numerical packages. Here we explain the design principles and currently supported features and present numerical examples in a range of applications.Comment: 20 pages, 8 figure

A Genome-Wide siRNA Screen to Identify Modulators of Insulin Sensitivity and Gluconeogenesis

BACKGROUND: Hepatic insulin resistance impairs insulin's ability to suppress hepatic glucose production (HGP) and contributes to the development of type 2 diabetes (T2D). Although the interests to discover novel genes that modulate insulin sensitivity and HGP are high, it remains challenging to have a human cell based system to identify novel genes. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes that modulate hepatic insulin signaling and HGP, we generated a human cell line stably expressing beta-lactamase under the control of the human glucose-6-phosphatase (G6PC) promoter (AH-G6PC cells). Both beta-lactamase activity and endogenous G6PC mRNA were increased in AH-G6PC cells by a combination of dexamethasone and pCPT-cAMP, and reduced by insulin. A 4-gene High-Throughput-Genomics assay was developed to concomitantly measure G6PC and pyruvate-dehydrogenase-kinase-4 (PDK4) mRNA levels. Using this assay, we screened an siRNA library containing pooled siRNA targeting 6650 druggable genes and identified 614 hits that lowered G6PC expression without increasing PDK4 mRNA levels. Pathway analysis indicated that siRNA-mediated knockdown (KD) of genes known to positively or negatively affect insulin signaling increased or decreased G6PC mRNA expression, respectively, thus validating our screening platform. A subset of 270 primary screen hits was selected and 149 hits were confirmed by target gene KD by pooled siRNA and 7 single siRNA for each gene to reduce G6PC expression in 4-gene HTG assay. Subsequently, pooled siRNA KD of 113 genes decreased PEPCK and/or PGC1alpha mRNA expression thereby demonstrating their role in regulating key gluconeogenic genes in addition to G6PC. Last, KD of 61 of the above 113 genes potentiated insulin-stimulated Akt phosphorylation, suggesting that they suppress gluconeogenic gene by enhancing insulin signaling. CONCLUSIONS/SIGNIFICANCE: These results support the proposition that the proteins encoded by the genes identified in our cell-based druggable genome siRNA screen hold the potential to serve as novel pharmacological targets for the treatment of T2D

Dynamic Air Target Threat Assessment Based on Interval-Valued Intuitionistic Fuzzy Sets, Game Theory, and Evidential Reasoning Methodology

In order to reduce the uncertainty of target threat assessment results and improve exact target assessment in the complicated and changeable air combat environment, a novel method based on the combination of interval-valued intuitionistic fuzzy sets (IVIFSs), game theory, and evidential reasoning methodology is proposed in this paper. First, the imprecise and fuzzy information of battlefield air target is expressed by IVIFS. Second, the optimal index weight is determined by the interval intuitionistic fuzzy entropy and game theory. And the time series weight is calculated by the inverse Poisson distribution method. Then, the target evaluation information at different times is dynamically fused through an evidential reasoning algorithm. Finally, the accuracy function is applied to obtain the threat ranking of all the targets. A case of the threat assessment of air targets is provided to demonstrate the implementation process of the method proposed in this paper. Simulation experiments show that in a rapidly evolving combat environment, this algorithm can effectively reduce the uncertainty of target threat assessment results. It provides us with a useful way for target threat assessment based on interval-valued intuitionistic fuzzy sets, game theory, and evidential reasoning methodology

Tracking the extracellular and intracellular antibiotic resistance genes across whole year in wastewater of intensive dairy farm

Monitoring the annual variation of antibiotic resistance genes (ARGs) in livestock wastewater is important for determining the high-risk period of transfer and spread of animal-derived antibiotic resistance into the environment. However, the knowledge regarding the variation patterns of ARGs, especially intracellular ARGs (iARGs) and extracellular ARGs (eARGs), over time in livestock wastewater is still unclear. Herein, we conducted a year-round study to trace the profiles of ARGs at a Chinese-intensive dairy farm, focusing on the shifts observed in different months. The results showed significant differences in the composition and variation between iARGs and eARGs. Tetracycline, sulfonamide, and macrolide resistance genes were the major types of iARGs, while cfr was the major type of eARG. The environmental adaptations of the host bacteria determine whether ARGs appear as intracellular or extracellular forms. The total abundance of ARGs was higher from April to September, which can be attributed to the favorable climatic conditions for bacterial colonization and increased antibiotic administration during this period. Integron was found to be highly correlated with most iARGs, potentially playing a role in the presence of these genes within cells and their similar transmission patterns in wastewater. The intracellular and extracellular bacterial communities were significantly different, primarily because of variations in bacterial adaptability to the high salt and anaerobic environment. The intracellular co-occurrence network indicated that some dominant genera in wastewater, such as Turicibacter, Clostridium IV, Cloacibacillus, Subdivision5_genera_incertae_sedis, Saccharibacteria_genera_incertae_sedis and Halomonas, were potential hosts for many ARGs. To the best of our knowledge, this study demonstrates, for the first time, the annual variation of ARGs at critical points in the reuse of dairy farm wastewater. It also offers valuable insights into the prevention and control of ARGs derived from animals

Construction of a virtual reality platform for computer-aided navigation Lingnan bone setting technique

ABSTRACTTo establish a standard Traditional Chinese medicine (TCM) bone setting technique, standardize the operation and inherit the TCM bone setting technique. This project was based on the interactive tracking of bone setting techniques with a dedicated position tracker, the motion tracking of bone setting techniques based on RGBD (Red Green Blue Depth) cameras, the digital analysis of bone setting techniques, and the design of the virtual reality platform for bone setting techniques. These key technical researches were combined to construct an interactive bone setting technique. The virtual simulation system can reproduce the implementation process of the expert’s bone setting technique. The user can observe the implementation of the manipulative technique from multiple angles; through human-computer interaction, the whole process of implementation of the bone setting technique can be simulated, and the movement and reduction of the affected bone can be observed at the same time. It can be used as a teaching and training system for assisting bone setting techniques. Students can use the system to carry out repeated self-training, and can instantly compare with the standard techniques of the expert database, breaking the traditional teaching mode of ‘expected and unspeakable’ and avoid directly using patients. Therefore, this research makes it possible to reduce teaching costs, reduce risks, improve teaching quality, and make up for the lack of teaching conditions. It is very positive for the inheritance of the traditional Chinese ‘intangible culture’ of bone setting techniques, and to promote the digitalization and standardization of bone setting techniques

Suppression of β Cell Energy Metabolism and Insulin Release by PGC-1α

β cell dysfunction is an important component of type 2 diabetes, but the molecular basis for this defect is poorly understood. The transcriptional coactivator PGC-1α mRNA and protein levels are significantly elevated in islets from multiple animal models of diabetes; adenovirus-mediated expression of PGC-1α to levels similar to those present in diabetic rodents produces a marked inhibition of glucose-stimulated insulin secretion from islets in culture and in live mice. This inhibition coincides with changes in metabolic gene expression associated with impaired β cell function, including the induction of glucose-6-phosphatase and suppression of GLUT2, glucokinase, and glycerol-3-phosphate dehydrogenase. These changes result in blunting of the glucose-induced rise in cellular ATP levels and membrane electrical activity responsible for Ca 2+ influx and insulin exocytosis. These results strongly suggest that PGC-1α plays a key functional role in the β cell and is involved in the pathogenesis of the diabetic phenotype