Structure Editor Research Articles

Improved prime editing allows for routine predictable gene editing in Physcomitrium patens.

Efficient and precise gene editing is the gold standard of any reverse genetic study. The recently developed prime editing approach, a modified CRISPR/Cas9 [clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein] editing method, has reached the precision goal but its editing rate can be improved. We present an improved methodology that allows for routine prime editing in the model plant Physcomitrium patens, whilst exploring potential new prime editing improvements. Using a standardized protoplast transfection procedure, multiple prime editing guide RNA (pegRNA) structural and prime editor variants were evaluated targeting the APT reporter gene through direct plant selection. Together, enhancements of expression of the prime editor, modifications of the 3' extension of the pegRNA, and the addition of synonymous mutation in the reverse transcriptase template sequence of the pegRNA dramatically improve the editing rate without affecting the quality of the edits. Furthermore, we show that prime editing is amenable to edit a gene of interest through indirect selection, as demonstrated by the generation of a Ppdek10 mutant. Additionally, we determine that a plant retrotransposon reverse transcriptase enables prime editing. Finally, we show for the first time the possibility of performing prime editing with two independently coded peptides.

CSDB/SNFG Structure Editor: An Online Glycan Builder with 2D and 3D Structure Visualization.

This article describes features, usage, and application of an CSDB/SNFG Structure Editor, a new online tool for quick and intuitive input of carbohydrate and derivative structures using Symbol Nomenclature for Glycans (SNFG). The Editor is built on a platform of the Carbohydrate Structure Database (CSDB) and relies on its online services via the dedicated web-API. The Editor allows building of oligo- and polymeric glycan structures and supports most features of natural glycans, such as underdetermined structures, alternative branches, repeating subunits, SMILES specification of atypical monomers, and others. The vocabulary of building blocks contains 600+ monomeric residues, including 327 monosaccharides. Support for SMILES allows input and visualization of chemical structures of virtually unlimited complexity. On the other hand, the interface follows the recognized GlycanBuilder style easy to novice users. The export feature includes support for CSDB Linear, GlycoCT, WURCS, SweetDB, and Glycam notations, SMILES codes, MOL/PDB atomic coordinate formats, raster and vector SNFG images, and on-the-fly visualization as 2D structural formulas and 3D molecular models. Integration of the Editor into any web-based glycoinformatics project is straightforward and simple, similarly to any other modern JavaScript application.

Twitter integration of chemistry software tools

Social media activity on a research article is considered to be an altmetric, a new measure to estimate research impact. Demonstrating software on Twitter is a powerful way to attract attention from a larger audience. Twitter integration of software can also lower the barriers to trying the tools and make it easier to save and share the output. We present three case studies of Twitter bots for cheminformatics: retrosynthetic analysis, 3D molecule viewer, and 2D chemical structure editor. These bots make software research more accessible to a broader range of people and facilitate the sharing of chemical knowledge, concepts, and ideas.

MFsim\u2014an open Java all-in-one rich-client simulation environment for mesoscopic simulation

MFsim is an open Java all-in-one rich-client computing environment for mesoscopic simulation with Jdpd as its default simulation kernel for Molecular Fragment (Dissipative Particle) Dynamics. The new environment comprises the complete preparation-simulation–evaluation triad of a mesoscopic simulation task and especially enables biomolecular simulation tasks with peptides and proteins. Productive highlights are a SPICES molecular structure editor, a PDB-to-SPICES parser for particle-based peptide/protein representations, a support of polymer definitions, a compartment editor for complex simulation box start configurations, interactive and flexible simulation box views including analytics, simulation movie generation or animated diagrams. As an open project, MFsim allows for customized extensions for different fields of research.

Developing the Guard Ring Topology of Power Silicon Diodes with a Blocking Voltage of up to 6.7 kV

High-voltage fast recovery diodes (FRDs) are characterized by a small forward voltage drop and low power dissipation. The main characteristics of such diodes is the reverse blocking voltage or the breakdown voltage. The aim of this work is to develop a guard ring topology allowing us to obtain the maximum possible blocking voltage of the diode and definite localization of the breakdown place under the conditions of the standard technological processes and without using new materials or substrates. The topology of the high-voltage part of silicon fast recovery power diodes is developed to obtain the maximum reverse blocking voltage. The calculations are carried out in the TCAD environment in the structure editor of which we included a program for the automatic creation of device models with dimensions of about several millimeters. The arrangement of guard rings is calculated according to the proposed principle allowing us to obtain power diodes with different breakdown voltages. The topology is developed so that the breakdown occurs under the edge of the active region, which guarantees the absence of catastrophic failures of the device. Power fast recovery diodes manufactured according to the proposed topology have the maximum reverse blocking voltage within the range of 3.3–6.7 kV, which indicates the reliability of the calculation methodology.

Model of HfO2/Al2O3 Dielectric ALNINNAlganmos HEMT for Power Application

The work involves to devise dielectric HfO2 /Al2O3MOS-HEMT stack to validate for the device structure through the refinement of mesh analysis. The structure of the AlN\InN\AlGaN HEMT MOS-HEMTs are designed and meshed using the script file in the Sentaurus structure editor. TheAlN\InN\AlGaN MOS-HEMTs output characteristic are examined for physics of MOS-HEMT in Hydrodynamic model TCAD. The amalgamation formation ofthe Al0.30GaN0.70 barrierinterface with the channelofhigh 2DEG density result in anincreaseddrain current density and high trans conductance. Additional the device performance of DC transfer characteristics, small signal analysis of AlN/InN/AlGaNMOS-HEMT are analyzed and simulated.

Structure Editors and Autonomous Agents

Rational agents are becoming prevalent in many domains, from data analysis to entertainment and games. The increased prevalence of agents has evolved new tools and techniques to work with and design new agents. One such technique is system simulation. Systems simulation is a technique an author can use to imitate tasks, processes, or systems, and in particular, agents. Systems simulation has a variety of uses, ranging from simulating ecological systems to entertainment, such as interactive narratives and digital games. However, many system simulators use specialized programming languages and require prior programming experience. This causes a disconnect between individuals with limited programming experience who wish to use the simulation tools, and the software itself. New users may find the specialized languages daunting, and the initial learning process too intense for the anticipated reward. This research strives to bridge the gap between system simulation tools and users with little to no programming experience. Future work includes a corpus of narrative and autonomous agent creation tools designed for users with little to no programming experience.

Challenges in Creating Online Exercises and Exams in Organic Chemistry.

e-Learning has become increasingly important in chemical education and online exams can be an attractive alternative to traditional exams written on paper, particularly in classes with a large number of students. Ten years ago, we began to set up an e-course complementing our lecture courses Organic Chemistry I and II within the open-source e-learning environment Moodle. In this article, we retrace a number of decisions we took over time, thereby illustrating the challenges one faces when creating online exercises and exams in (organic) chemistry. Special emphasis is put on the development of MOSFECCS (MOlecular Structural Formula Editor and Calculator of Canonical SMILES), our new editor for drawing structural formulae and converting them to alphanumeric SMILES codes that can be submitted as answers to e-problems. Convinced that the possibility for structure input is essential to set up sensible chemistry quizzes and exams, and realising that existing tools present major flaws in an educational context, we decided to embark on the implementation of MOSFECCS which takes into account a number of didactic aspects.

Hazelnut: a bidirectionally typed structure editor calculus

Structure editors allow programmers to edit the tree structure of a program directly. This can have cognitive benefits, particularly for novice and end-user programmers. It also simplifies matters for tool designers, because they do not need to contend with malformed program text. This paper introduces Hazelnut, a structure editor based on a small bidirectionally typed lambda calculus extended with holes and a cursor . Hazelnut goes one step beyond syntactic well-formedness: its edit actions operate over statically meaningful incomplete terms. Naïvely, this would force the programmer to construct terms in a rigid "outside-in" manner. To avoid this problem, the action semantics automatically places terms assigned a type that is inconsistent with the expected type inside a hole. This meaningfully defers the type consistency check until the term inside the hole is finished . Hazelnut is not intended as an end-user tool itself. Instead, it serves as a foundational account of typed structure editing. To that end, we describe how Hazelnut's rich metatheory, which we have mechanized using the Agda proof assistant, serves as a guide when we extend the calculus to include binary sum types. We also discuss various interpretations of holes, and in so doing reveal connections with gradual typing and contextual modal type theory, the Curry-Howard interpretation of contextual modal logic. Finally, we discuss how Hazelnut's semantics lends itself to implementation as an event-based functional reactive program. Our simple reference implementation is written using js_of_ocaml.

Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement

Exercise is effective for prevention and management of acute and chronic health conditions. However, trial descriptions of exercise interventions are often suboptimal, leaving readers unclear about the content of effective...

A Study on Self-Heating and Mutual Thermal Coupling in SiGe Multi-Finger HBTs

In this paper, the self-heating and mutual thermal coupling in a state-of-the-art SiGe:C multi-finger heterojunction bipolar transistor (HBT) was investigated in static dc operation conditions. Multi-finger HBT structure was created using Sentaurus structure editor with dimensions similar to the layout of SiGe:C multi-finger HBTs in ST-Microelectronics BiCMOS55 (B55) technology (f T > 300 GHz, f max > 400 GHz) as per ST’s BiCMOS55 process design kit guidelines. Three-dimensional thermal technology computer aided design (TCAD) simulations were carried out to obtain the temperature distribution in static dc operation. The lattice temperature (T Lattice) and heat flux (F Heat) distribution inside the device were studied. The impact of back-end-of-line (BEOL) layers on static thermal behavior of the state-of-the-art SiGe:C multi finger HBTs was also investigated. The temperature dependent thermal resistance of different fingers of the trench isolated SiGe multi-finger HBT was extracted without and with back-end-of-line (BEOL) effect. An electro-thermal dc compact model of self-heating and mutual thermal coupling in multi-finger HBTs was proposed and applied to compare the modeling results with the TCAD simulation results. Very good agreement was achieved between results obtained from TCAD simulation and those obtained from compact model-based simulation.

In-silico bonding schemes to encode chemical bonds involving sharing of electrons in molecular structures

Encoding of covalent and coordinate covalent bonds in molecular structures using ground state valence electronic configuration is achieved. The bonding due to electron sharing in the molecular structures is described with five fundamental bonding categories viz. uPair–uPair, lPair–uPair, uPair–lPair, vPair–lPair, and lPair–lPair. The involvement of lone pair electrons and the vacant electron orbitals in chemical bonding are explained with bonding schemes namely “target vacant promotion”, “source vacant promotion”, “target pairing promotion”, “source pairing promotion”, “source cation promotion”, “source pairing double bond”, “target vacant occupation”, and “double pairing promotion” schemes. The bonding schemes are verified with a chemical structure editor. The bonding in the structures like ylides, PCl5, SF6, IF7, N-Oxides, BF4−, AlCl4− etc. are explained and encoded unambiguously. The encoding of bonding in the structures of various organic compounds, transition metals compounds, coordination complexes and metal carbonyls is accomplished.

Database-oriented annotation of early modern plays: a proposal

This essay proposes that the electronic texts of plays constituting a database-collection (in this case early modern drama) should be “annotated” by marking up not only its structural components but also the editorial annotations about a given feature or aspect of the play (usually included in the commentary notes of print editions), and that these annotations should be conceived having in mind the functionalities of a database. By marking up both the text's structural components and editor's information they constitute related data to be processed by the computer for searches and statistical analysis. This implies that texts should not be annotated individually and independently from the other anthologized works, but rather as part of an organized collection of data that, adequately encoded, will allow users to make queries into the whole database. A second section of the essay discusses three encoding mechanisms, based on the Guidelines of the Text Encoding Initiative, necessary to mark up these “annotations,” and possible ad hoc extensions of the TEI schema in order to represent the annotated features. Finally, a third section comments on practical examples showing how to encode a set of features: scene location, image, theme, allusion, proverb, wordplay, grammar, swearing expression, address form, as well as features covered by the TEI Guidelines such as roles, stage directions, names and place-names, verse form and textual issues.

Generating 3D Visual Language Editors: Encapsulating Interaction Techniques in Visual Patterns

The implementation of three-dimensional visual languages requires a wide range of conceptual and technical knowledge on issues for 3D graphics and textual language processing. Our generator framework DEViL3D incorporates such knowledge and supports the design of visual 3D languages and their implementation from high-level specifications. Such 3D languages arise from different modeling domains that make use of three-dimensional representations, e.g. the "ball-and-stick" models of molecules. The front-end of a 3D language implementation is a dedicated 3D graphical structure editor, which offers interaction and navigation techniques to construct programs in their domain. These techniques allow to manipulate the 3D program directly using operations to insert, move, and restructure objects. We have developed canned solutions for all such techniques that are encapsulated in visual patterns, which are provided by our generator. The designer of a particular 3D language only has to apply visual patterns to constructs of the abstract syntax, which defines the basic structure of the language. We have complemented our development with a usability study. Participants had to solve several tasks with different interaction or navigation techniques. Furthermore, we equipped the 3D editors with the opportunity to let users gain an immersive 3D perception by using stereoscopic hardware.

Facilitate earth science data interoperability using the SCIDIP-ES data virtualisation toolkit

Ensuring long-term accessibility of Earth Science archive data is a recurrent issue for data centers. Heterogeneity of data adds particular challenges. The Data Virtualisation Toolkit (DVT) has been developed by the SCIDIP-ES project to support long-term access and use of heterogeneous Earth Science (ES) data in a format-independent manner. DVT provides four key functions: (a) edit format description, (b) interpret bit stream into data values using the format description, (c) construct legacy information from data values via coherent information models, and (d) visualize the retrieved legacy information if the information model is supported by the visualization component. The toolkit incorporates a tree structure editor, a bit stream interpretation engine, information models in XQuery, and a visualization component. DVT is designed to provide long term access to Earth Science data with the proper representation information which contains the technical knowledge required for interpretation. A trial application using both vector and raster data shows that DVT could provide interoperable solutions to support the long-term preservation of ES data. This paper reports on the concept, development, and implementation of DVT.

SMMRNA: a database of small molecule modulators of RNA.

We have developed SMMRNA, an interactive database, available at http://www.smmrna.org, with special focus on small molecule ligands targeting RNA. Currently, SMMRNA consists of ∼770 unique ligands along with structural images of RNA molecules. Each ligand in the SMMRNA contains information such as Kd, Ki, IC50, ΔTm, molecular weight (MW), hydrogen donor and acceptor count, XlogP, number of rotatable bonds, number of aromatic rings and 2D and 3D structures. These parameters can be explored using text search, advanced search, substructure and similarity-based analysis tools that are embedded in SMMRNA. A structure editor is provided for 3D visualization of ligands. Advance analysis can be performed using substructure and OpenBabel-based chemical similarity fingerprints. Upload facility for both RNA and ligands is also provided. The physicochemical properties of the ligands were further examined using OpenBabel descriptors, hierarchical clustering, binning partition and multidimensional scaling. We have also generated a 3D conformation database of ligands to support the structure and ligand-based screening. SMMRNA provides comprehensive resource for further design, development and refinement of small molecule modulators for selective targeting of RNA molecules.

A Unified Proteochemometric Model for Prediction of Inhibition of Cytochrome P450 Isoforms

A unified proteochemometric (PCM) model for the prediction of the ability of drug-like chemicals to inhibit five major drug metabolizing CYP isoforms (i.e. CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) was created and made publicly available under the Bioclipse Decision Support open source system at www.cyp450model.org. In regards to the proteochemometric modeling we represented the chemical compounds by molecular signature descriptors and the CYP-isoforms by alignment-independent description of composition and transition of amino acid properties of their protein primary sequences. The entire training dataset contained 63 391 interactions and the best PCM model was obtained using signature descriptors of height 1, 2 and 3 and inducing the model with a support vector machine. The model showed excellent predictive ability with internal AUC = 0.923 and an external AUC = 0.940, as evaluated on a large external dataset. The advantage of PCM models is their extensibility making it possible to extend our model for new CYP isoforms and polymorphic CYP forms. A key benefit of PCM is that all proteins are confined in one single model, which makes it generally more stable and predictive as compared with single target models. The inclusion of the model in Bioclipse Decision Support makes it possible to make virtual instantaneous predictions (∼100 ms per prediction) while interactively drawing or modifying chemical structures in the Bioclipse chemical structure editor.

Design & Development of a New and Efficient Approach for Line Text Editing in Turbo Pascal 5.5 for Windows/Netware/MS-DOS*

Text editors come in the forms viz. Line editors, Stream editors, Screen editors, Word processors, Structure editors, etc. There are many text editors provided with Windows viz. Notepad, WordPad, Microsoft Office Word, etc. The MS-DOS editors viz. EDLIN and EDIT also work in Windows. MS-DOS had very good word processors viz. Word Star, Word Perfect, etc. All the editors which work in MS-DOS, also work in the Novell’s Netware OS as well. But none of the above editors is interactive. The process of entering the programs/text shall be greatly enhanced, for the newcomers, if the editor is an interactive one. This paper gives the design & development of a new and efficient approach for line text editing, the most basic and fundamental editing, in Turbo Pascal 5.5 for Windows/Netware/MS-DOS OS. It is proposed to give a new, interactive, and more user friendly approach to line text editing for document / non document (program) files using singly- linked lists. A menu driven program is designed and developed which works like an IDE, Integrated Development Environment, available in most of the programming languages viz. Turbo C, Turbo Pascal, etc . The program displays all the options and once a user chooses a particular option, he is prompted further interactively. The program is fully tested on Windows XP, with total RAM = 256 MB and shall work efficiently on Novell’s Netware and MS-DOS as well. This research work has, in all, twenty eight options and is academically (not available in any book) very useful for the Computer Science & Engineering and Information Technology disciplines.

MyChemise: A 2D drawing program that uses morphing for visualisation purposes

MyChemise (My Chemical Structure Editor) is a new 2D structure editor. It is designed as a Java applet that enables the direct creation of structures in the Internet using a web browser. MyChemise saves files in a digital format (.cse) and the import and export of .mol files using the appropriate connection tables is also possible.MyChemise is available as a free online version in English and German. The MyChemise GUI is designed to be user friendly and can be used intuitively. There is also an English and German program description available as a PDF file.In addition to the known ways of drawing chemical structure formulas, there are also parts implemented in the program that allow the creation of different types of presentation. The morphing module uses this technology as a component for dynamic visualisation. For example, it enables a clear and simple illustration of molecule vibrations and reaction sequences.

Ketcher: web-based chemical structure editor

Ketcher is an open-source web-based chemical structure editor developed by SciTouch LLC. Being written on pure JavaScript it incorporates high performance, good portability and light weight. Editor supports late versions of all most popular browsers, such as Internet Explorer, Firefox, Safari, Opera and Chrome. It is developed with minimum third-party code to remain its light weight. It is platform-independent and can be used as a structure viewer as well. SciTouch keeps on working to add more features to Ketcher in near future. Ketcher is available under Affero GPL license. Features: • Standalone mode. Ketcher supports standalone mode in which no server support is required. • Scalable Vector Graphics (SVG) for rendering. Ketcher uses SVG to achieve the best quality of in-browser chemical structure rendering. SVG standard is supported by most of modern browsers and provides smooth and light-weight drawing. IE rendering is based on VML (Vector Markup Language) instead. • SMILES strings. SMILES is a compact format for chemical structure representation. Ketcher gives you ability to load and save structure in this useful format. • Automatic layout (clean up). Server-side structure layout is implemented basing on Indigo cheminformatics library with a Python wrapper. Indigo provides fast 2D structure representation which satisfies common chemical drawing standards. • And also: MDL (Symyx) molfiles support, hot keys, stereochemistry support, complete undo/redo history and much more. Ketcher web site: http://scitouch.net/ketcher Try Ketcher demo: http://scitouch.net/ketcher-demo/ketcher.html