Location: Electronic Resource- 

Montgomery Blencowe
Dec 23, 2020; 0:jlr.RA120000713v1-jlr.RA120000713
Research Articles

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

The Sigrity and Systems Analysis (SIGRITY/SYSANLS) 2024.1 release is now available for download at Cadence Downloads . For the list of CCRs fixed in this release, see the README.txt file in the installation hierarchy. SIGRITY/SYSANLS 2024.1 Here is a list of some of the key updates in the SIGRITY/SYSANLS 2024.1 release: For more details about these and all the other new and enhanced features introduced in this release , refer to the following document: Sigrity Release Overview and Common Tools What's New . Supported Platforms and Operating Systems Platform and Architecture X86_64 (lnx86) Windows (64 bit) Development OS RHEL 8.4 Windows Server 2022 Supported OS RHEL 8.4 and above RHEL 9 SLES 15 (SP3 and above) Windows 10 Windows 11 Windows Server 2019 Windows Server 2022 Systems Analysis 2024.1 Clarity 3D Solver Clarity 3D Layout Structure Optimization Workflow : A new workflow, Clarity 3D Layout Structure Optimization Workflow, has been added to Clarity 3D Layout. This workflow integrates Allegro PCB Designer with Clarity 3D Layout for high-speed structure optimization. Component Geometry Model Editor : The new Clarity 3D Layout editor lets you set up ports, solder bumps/balls/extrusions, and two-terminal and multi-terminal circuits using a single GUI. Coaxial Open Port Option Added to Port Setup Wizard : The Coaxial Open Port option lets you create ports for each target net pin and reference net pin in Clarity 3D Layout. The nearby reference net pins are then used as a reference for each target net pin, reducing the number of ports needed. In addition, the ports of unused reference net pins are shorted to the ground. Parametric Import Option Added : Two new options, Parametric Import and Default Import , have been added to the Tools – Launch Clarity3DWorkbench menu. The Parametric Import option lets you import the design along with its parameters into Clarity 3D Workbench. The Default Import option lets you ignore the parameters when importing the design into Clarity 3D Workbench. Component Library Added to Generate 3D Components : Clarity 3D Workbench now includes a new component library that lets you use predefined 3D component templates or add existing 3D components to create 3D designs and simulation models. AI-Powered Content Search Capability : Clarity 3D Workbench and Clarity 3D Transient Solver now support an AI-powered capability for searching the content and displaying relevant information. Expression Parser to Handle Undefined Parameters : Clarity 3D Workbench and Clarity 3D Transient Solver support writing expressions or equations containing undefined parameters in the Property window to describe a simulation variable. The improved expression parser automatically detects any undefined parameter in an expression and prompts users to specify their values. This capability lets you define a model or a simulation variable as a function instead of specifying static values. For detailed information, refer to Clarity 3D Layout User Guide and Clarity 3D Workbench User Guide on the Cadence Support portal. Clarity 3D Transient Solver Mesh Processing Improved to Simulate Large Use Cases : Clarity 3D Transient Solver leverages a new meshing algorithm that enhances overall mesh processing, specifically for large designs and use cases. The new algorithm dramatically improves the mesh quality, minimum mesh size, number of mesh key points, total mesh number, and memory usage. Advanced Material Processing Engine : The material processing capability has been enhanced to handle thin outer metal, which previously resulted in open and short issues in some designs. In addition, the material processing engine offers improved mode extraction for particular use cases, including waveguide and coaxial designs. Characteristic Impedance Calculation Improved : The solver engine now uses a new analytical calculation method to calculate the characteristic impedance of coaxial designs with improved accuracy. For detailed information, refer to Clarity 3D Transient Solver User Guide on the Cadence Support portal. Celsius Studio Celsius Interchange Model Introduced : Celsius Studio now supports Celsius Interchange Model generation, which is a 3D model derived from detailed physical designs for multi-physics and multi-scale analysis. This Celsius Interchange Model file ( .cim ) serves as a design information carrier across Celsius Studio tools, enabling a variety of simulation and analysis tasks . Celsius 3DIC Thermal Workflow Improvements : The Thermal Simulation workflows in Celsius 3DIC have been significantly enhanced. Key improvements include: Advanced Power Setup with Transient Power Function and Multi Mode options Enhanced GUI for the Mesh Control and Simulation Control tabs Improved meshing capabilities Celsius Interchange Model ( .cim ) generation Material library support for block and connections Import of Heat Transfer Coefficients (HTCs) from a CFD file Bump creation through the Bump Array Wizard Layer Stackup CSV file generation Celsius 3DIC Warpage and Stress Workflow Enhancements : The Warpage and Stress workflow in Celsius 3DIC has undergone significant improvements, such as: Improved multi-stage warpage simulation flow for 3DIC packaging process Enhanced GUI for the Mesh Control , Simulation Control , and Stress Boundary Conditions tabs Support for large deformations and temperature profiles Bump creation through the Bump Array Wizard New constraint types Enhanced meshing capabilities Geometric Nonlinearity Support in Warpage and Stress Analysis : Large deformation analysis is now supported in warpage and stress studies. This study uses the Total Lagrangian approach to model geometric nonlinearities in simulation, which allows accurate prediction of final deformations. Thermal Network Extraction and Simulation : In the solid extraction flow in Celsius 3D Workbench, you can now import area-based power map files to create terminals. For designs with multiple blocks, this capability allows automatic terminal creation, eliminating the need to manually create and set up 2D sheets individually. Additionally, thermal throttling feature is now supported in Celsius Thermal Network. This makes it ideal for preliminary analyses or when a quick estimation is required. It runs significantly faster than 3D models, allowing for quicker iterations and more efficient decision-making. For detailed information, refer to the Celsius 3DIC User Guide , Celsius Layout User Guide and Celsius 3D Workbench User Guide on the Cadence Support portal. Sigrity 2024.1 Layout Workbench Improved Graphical User Interface : A new option, Use Improved User Interface , has been added in the Themes page of the Options dialog box in the Layout Workbench GUI. In the new GUI, the toolbar icons and menu options have been enhanced and rearranged. For detailed information, refer to Layout Workbench User Guide on the Cadence Support portal. Broadband SPICE Python Script Integration with Command Line for Simulation Tasks : Broadband SPICE lets you run Python scripts directly from the command line for performing simulation and analysis. The new -py and *.py options make it easier to integrate Python scripts with the command-line operations. This update streamlines the process of automating and customizing simulations from the command line, which makes your simulation tasks faster and easier. For detailed information, refer to Broadband SPICE User Guide on the Cadence Support portal. Celsius PowerDC Block Power Assignment (BPA) File Format Support : PowerDC now supports the BPA file format. Similar to the Pin Location (PLOC) file, the BPA file is a current assignment file that defines the total current of a power grid cell, which is then equally distributed across the power pins within the cell. This provides better control over the power distribution. Ability to Run Multiple IR Drop Cases Sequentially : You can now select multiple result sinks from the Current-Limited IR Drop flow and run IR Drop analysis for them sequentially. PowerDC automatically runs the simulations in sequence after you select multiple result sinks. This saves time by automating the process. Enhanced Support for Mixed Conversion Devices : PowerDC now supports mixing different conversion devices, such as switching regulators and linear regulators within a single DC-DC/LDO instance. This enhancement offers added flexibility by letting you configure each instance in your design according to your specific needs. For detailed information, refer to PowerDC User Guide on the Cadence Support portal. PowerSI Monte Carlo Method Added : A new option, Monte Carlo Method, has been added in the Optimality dialog box. This option lets you create multiple random samples to depict variations in the input parameters and assess the output. Channel Check Optimization Added : The S-Parameter Assessment workflow in PowerSI now supports Channel Check Optimization . It uses the AI-driven Multidisciplinary Analysis and Optimization (MDAO) technology that lets you optimize your design quickly and efficiently with no accuracy loss. For detailed information, refer to PowerSI User Guide on the Cadence Support portal. SPEEDEM Multi-threaded Matrix Solver Support Added : The Enable Multi-threaded Matrix Solver check box has been added that lets you accelerate the simulation speed for high-performance computing. This check box provides two options, Automatic and Always, to include the -lhpc4 or -lhpc5 parameter, respectively, in the SPEEDEM Simulator (SPDSIM) before running the simulation. For detailed information, refer to the SPEEDEM User Guide on the Cadence Support portal. XtractIM Options to Skip or Calculate Special DC-R Simulation Results : The Skip DC_R of Each Path and Only DC_R of Each Path options have been added to the Setup menu. Skip DC_R of Each Path : This option lets you skip the calculation of the DC-R result during the simulation. Other results, such as SPICE T-model , RL_C of Each Path , Coupling of Each Path , etc., are still calculated. Only DC_R of Each Path : This option lets you calculate the DC-R result only during the simulation. Other results, such as SPICE T-model , RL_C of Each Path , Coupling of Each Path , etc., are not calculated. Color Assignment for Pin Matching : The MCP Auto Connection window includes the Display Color Editor , which lets you assign a color for pin matching. It helps you easily identify the matching pins in the left and right sections of the MCP Auto Connection window . Ability to Save Simulations Individually : The Save each simulation individually check box has been added to the Tools - Options - Edit Options - Simulation (Basic) - General form. Select this check box and run the simulation to generate a simulation results folder containing files and logs with a timestamp for each simulation. Reuse of SPD File Settings : The XtractIM setup check box lets you import an existing package setup to reuse the configurations and settings from one .spd file to another. For detailed information, refer to XtractIM User Guide on the Cadence Support portal. Documentation Enhancements Cloud-Based Help System Upgraded The cloud-based help system, Doc Assistant, has been upgraded to version 24.10, which contains several new features and enhancements over the previous 2.03 version. Sigrity Release Team Please send your questions and feedback to sigrity_rmt@cadence.com .

The Sigrity and Systems Analysis (SIGRITY/SYSANLS) 2022.1 HF2 release is now available for download at Cadence Downloads. For the list of CCRs fixed in the 2022.1 HF2 release, see the README.txt file in the installation hierarchy.(read more)

Microwaves & RF's David Maliniak interviews Sherry Hess of Cadence about recently announced products of Optimality and OnCloud.(read more)

Announcement Number: SE-18-EI-00844-DE
Closing Date: 13 November 2018

Announcement Number: SE-18-EI-00844-MP
Closing Date: 13 November 2018

Geoffrey M. Boynton
Jul 1, 1996; 16:4207-4221
Articles

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.

Online Resource

Online Resource