AI-driven design automation is the use of artificial intelligence (AI) to automate and improve different parts of the electronic design automation (EDA) process. It is particularly important in the design of integrated circuits (chips) and complex electronic systems, where it can potentially increase productivity, decrease costs, and speed up design cycles. AI Driven Design Automation uses several methods, including machine learning, expert systems, and reinforcement learning. These are used for many tasks, from planning a chip's architecture and logic synthesis to its physical design and final verification. == History == === 1980s–1990s: Expert systems and early experiments === The use of AI for design automation originated in the 1980s and 1990s, mainly with the creation of expert systems. These systems tried to capture the knowledge and practical rules used by human design experts, and used these rules, along with reasoning engines, to direct the design process. A notable early project was the ULYSSES system from Carnegie Mellon University. ULYSSES was a CAD tool integration environment that let expert designers turn their design methods into scripts that could be run automatically. It treated design tools as sources of knowledge that a scheduler could manage. Another example was the ADAM (Advanced Design AutoMation) system at the University of Southern California, which used an expert system called the Design Planning Engine. This engine figured out design strategies on the fly and handled different design jobs by organizing specialized knowledge into structured formats called frames. Other systems like DAA (Design Automation Assistant) used a rule-based approach for specific jobs, such as register transfer level (RTL) design for systems like the IBM 370. Researchers at Carnegie Mellon University also created TALIB, an expert system for mask layout that used over 1200 rules, and EMUCS/DAA for CPU architectural design which used about 70 rules. These projects showed that AI worked better for problems where relatively few rules were required to describe much larger amounts of data. At the same time, there was a surge of tools called silicon compilers like MacPitts, Arsenic, and Palladio. They used algorithms and search techniques to explore different design paradigms. This was another way to automate design, even if it was not always based on expert systems. Early tests with neural networks in VLSI design also happened during this time, although they were not as common as systems based on rules. === 2000s: Introduction of machine learning === In the 2000s, interest in AI for design automation increased. This was mostly because of better machine learning (ML) algorithms and more available data from design and manufacturing. For example, they were used to model and reduce the effects of small manufacturing differences in semiconductor devices. This became very important as the size of components on chips became smaller. The large amount of data created during chip design provided the foundation needed to train smarter ML models. This allowed for predicting outcomes and optimizing in areas that were hard to automate before. === 2016–2020: Reinforcement learning and large scale initiatives === A major turning point happened in the mid to late 2010s, sparked by successes in other areas of AI. The success of DeepMind's AlphaGo in mastering the game of Go inspired researchers. They began to apply reinforcement learning (RL) to difficult EDA problems. These problems often require searching through many options and making a series of decisions. In 2018, the U.S. DARPA started the Intelligent Design of Electronic Assets (IDEA) program. A main goal of IDEA was to create a fully automated layout generator that required no human intervention, able to produce a chip design ready for manufacturing from RTL specifications in 24 hours. Another big initiative was the OpenROAD project, a large effort under IDEA led by UC San Diego with industry and university partners, aimed to build an open source, independent toolchain. It used machine learning, parallelization and divide and conquer approaches. A much-publicized but controversial demonstration of RL's potential came from Google researchers between 2020 and 2021. They created a deep reinforcement learning method for planning the layout of a chip, known as floorplanning. They reported that this method created layouts that were as good as or better than those made by human experts, and it did so in less than six hours. This method used a type of network called a graph convolutional neural network. It showed that it could learn general patterns that could be applied to new problems, getting better as it saw more chip designs. The technology was later used to design Google's Tensor Processing Unit (TPU) accelerators. However, in the original paper, the improvement (if any) from AI was not demonstrated. There was no comparison with existing non-AI tools performing the same task, and since the data is proprietary, no ability for anyone else to perform this comparison. Various efforts to reproduce the AI algorithm, and compare its results with various commercial and academic tools, have yielded mixed results with no conclusive advantage to AI. === 2020s: Autonomous systems and agents === Entering the 2020s, the industry saw the commercial launch of autonomous AI driven EDA systems. For example, Synopsys launched DSO.ai (Design Space Optimization AI) in early 2020, calling it the first autonomous artificial intelligence application for chip design in the industry. This system uses reinforcement learning to search for the best ways to optimize a design within the huge number of possible solutions, trying to improve power, performance, and area (PPA). By 2023, DSO.ai had been used to produce over 100 commercial chips, showing mainstream adoption. Synopsys later grew its AI tools into a suite called Synopsys.ai. The goal was to use AI in the entire EDA workflow, including verification and testing. These advancements, which combine modern AI methods with cloud computing and large data resources, have led to talks about a new phase in EDA. Industry experts and participants sometimes call this 'EDA 4.0'. This new era is defined by the widespread use of AI and machine learning to deal with growing design complexity, automate more of the design process, and help engineers handle the huge amounts of data that EDA tools create. The purpose of EDA 4.0 is to optimize product performance, get products to market faster and make development and manufacturing smoother through intelligent automation. == Applications == Artificial intelligence (AI) is now used in many stages of the electronic design workflow. It aims to improve productivity, get better results, and handle the growing complexity of modern integrated circuits. AI helps designers from the very first ideas about architecture all the way to manufacturing and testing. === High level synthesis and architectural exploration === In the first phases of chip design, AI helps with High Level Synthesis (HLS) and exploring different system level design options (DSE). These processes are key for turning general ideas into detailed hardware plans. AI algorithms, often using supervised learning, are used to build simpler, substitute models. These models can quickly guess important design measurements like area, performance, and power for many different architectural options or HLS settings. For example, the Ithemal tool uses deep neural networks to estimate how fast basic code blocks will run, which helps in making processor architecture decisions. Similarly, PRIMAL uses machine learning estimate power use at the register transfer level (RTL), giving early information about how much power the chip will use. Reinforcement learning (RL) and Bayesian optimization are also used to guide the DSE process. They help search through the many parameters to find the best HLS settings or architectural details like cache sizes. LLMs are also being tested for creating architectural plans or initial C code for HLS, as seen with GPT4AIGChip. === Logic synthesis and optimization === Logic synthesis starts from a high level hardware description and generates an optimized list of electronic gates, known as a gate level netlist, that is ready for placement, routing, and then construction in a specific manufacturing process. AI methods help with different parts of this process, including logic optimization, technology mapping, and making improvements after mapping. Supervised learning, especially with Graph Neural Networks (GNNs), is good at handling data or problems that can be represented as graphs. Since circuit diagrams are instances of directed graphs, supervised learning can help create models that predict design properties like power or error rates in circuits. In logic synthesis and optimization reinforcement learning is used to perform logic optimization directly. In some cases ag
Joox
Joox (stylised in all caps) is a music streaming service owned by Tencent, launched in January 2015. Joox is the biggest music streaming app in Asian markets such as Hong Kong, Macau, Indonesia, Malaysia, Myanmar, Thailand and also in South Africa before it was shut down in early 2022. Joox is a freemium service, providing most of its songs free, while some songs are only available for premium users, offered via paid subscriptions or by doing different tasks offered. In 2017, Joox launched their service in their first non-Asian market, South Africa, which for an unknown reason shut down five years later. The service now accounts for more than 50% of all music streaming app downloads in their Asian markets. The number of music-streaming users in Hong Kong, Macau, Malaysia, Thailand, Myanmar and Indonesia was expected to reach 87 million by 2020. == Background == Before the emergence of Joox, Tencent owned QQ Music, one of the largest music streaming and download service in China. In 2015, they introduced Joox as their expansion of music services to overseas market instead of mainland China, starting first in Hong Kong. Instead of providing free services by playing audio ads to users like Spotify, another major music service, Joox focused on banner ads, splash ads and other advertising methods such as category playlists and in-app skins. They claimed it as a success. Joox offered their premium VIP access to DStv subscribers free of charge. DStv is the sister company to Tencent and is the primary pay-TV provider in South Africa. In November 2021, it was announced that Joox will stop streaming in South Africa in March 2022.
Comparison of vector graphics editors
A number of vector graphics editors exist for various platforms. Potential users of these editors will make comparisons based on factors such as the availability for the user's platform, the software license, the feature set, the merits of the user interface (UI) and the focus of the program. Some programs are more suitable for artistic work while others are better for technical drawings. Another important factor is the application's support of various vector and bitmap image formats for import and export. The tables in this article compare general and technical information for a number of vector graphics editors. See the article on each editor for further information. This article is neither all-inclusive nor necessarily up-to-date. == Some editors in detail == Adobe Fireworks (formerly Macromedia Fireworks) is a vector editor with bitmap editing capabilities with its main purpose being the creation of graphics for Web and screen. Fireworks supports RGB color scheme and has no CMYK support. This means it is mostly used for screen design. The native Fireworks file format is editable PNG (FWPNG or PNG). Adobe Fireworks has a competitive price, but its features can seem limited in comparison with other products. It is easier to learn than other products and can produce complex vector artwork. The Fireworks editable PNG file format is not supported by other Adobe products. Fireworks can manage the PSD and AI file formats which enables it to be integrated with other Adobe apps. Fireworks can also open FWPNG/PNG, PSD, AI, EPS, JPG, GIF, BMP, TIFF file formats, and save/export to FWPNG/PNG, PSD, AI (v.8), FXG (v.2.0), JPG, GIF, PDF, SWF and some others. Some support for exporting to SVG is available via a free Export extension. On May 6, 2013, Adobe announced that Fireworks would be phased out. Adobe Flash (formerly a Macromedia product) has straightforward vector editing tools that make it easier for designers and illustrators to use. The most important of these tools are vector lines and fills with bitmap-like selectable areas, simple modification of curves via the "selection" or the control points/handles through "direct selection" tools. Flash uses Actionscript for OOP, and has full XML functionality through E4X support. Adobe FreeHand (formerly Macromedia Freehand and Aldus Freehand) is mainly used by professional graphic designers. The functionality of FreeHand includes the flexibility of the application in the wide design environment, catering to the output needs of both traditional image reproduction methods and to contemporary print and digital media with its page-layout capabilities and text attribute controls. Specific functions of FreeHand include a superior image-tracing operation for vector editing, page layout features within multiple-page documents, and embedding custom print-settings (such as variable halftone-screen specifications within a single graphic, etc.) to each document independent of auxiliary printer-drivers. User-operation is considered to be more suited for designers with an artistic background compared to designers with a technical background. When being marketed, FreeHand lacked the promotional backing, development and PR support in comparison to other similar products. FreeHand was transferred to the classic print group after Macromedia was purchased by Adobe in 2005. On May 16, 2007, Adobe announced that no further updates to Freehand would be developed but continues to sell FreeHand MX as a Macromedia product. FreeHand continues to run on Mac OS X Snow Leopard (using an Adobe fix) and on Windows 7. For macOS, Affinity Designer is able to open version 10 & MX Freehand files. Adobe Illustrator is a commonly used editor because of Adobe's market dominance, but is more expensive than other similar products. It is primarily developed consistently in line with other Adobe products and is best integrated with Adobe's Creative Suite packages. The ai file format is proprietary, but some vector editors can open and save in that format. Illustrator imports over two dozen formats, including PSD, PDF and SVG, and exports AI, PDF, SVG, SVGZ, GIF, JPG, PNG, WBMP, and SWF. However, the user must be aware of unchecking the "Preserve Illustrator Editing Capabilities" option if generating interoperable SVG files is desired. Affinity Designer by Serif Europe (the successor to their previous product, DrawPlus) is non-subscription-based software that is often described as an alternative to Adobe Illustrator. The application can open Portable Document Format (PDF), Adobe Photoshop, and Adobe Illustrator files, as well as export to those formats and to the Scalable Vector Graphics (SVG) and Encapsulated PostScript (EPS) formats. It also supports import from some Adobe Freehand files (specifically versions 10 & MX). Apache OpenOffice Draw is the vector graphics editor of the Apache OpenOffice open source office suite. It supports many import and export file formats and is available for multiple desktop operating systems. Boxy SVG is a chromium-based vector graphics editor for creating illustrations, as well as logos, icons, and other elements of graphic design. It is primarily focused on editing drawings in the SVG file format. The program is available as both a web app and a desktop application for Windows, macOS, ChromeOS, and Linux-based operating systems. Collabora Online Draw is the vector graphics editor of the Collabora Online open source office suite. It supports many import and export file formats and is accessible via any modern web browser, it also supports desktop editing features, Collabora Office is available for desktop and mobile operating systems, it is the enterprise ready version of LibreOffice. ConceptDraw PRO is a business diagramming tool and vector graphics editor available for both Windows and macOS. It supports multi-page documents, and includes an integrated presentation mode. ConceptDraw PRO supports imports and exports several formats, including Microsoft Visio and Microsoft PowerPoint. Corel Designer (originally Micrografx Designer) is one of the earliest vector-based graphics editors for the Microsoft Windows platform. The product is mainly used for the creation of engineering drawings and is shipped with extensive libraries for the needs of engineers. It is also flexible enough for most vector graphics design applications. CorelDRAW is an editor used in the graphic design, sign making and fashion design industries. CorelDRAW is capable of limited interoperation by reading file formats from Adobe Illustrator. CorelDRAW has over 50 import and export filters, on-screen and dialog box editing and the ability to create multi-page documents. It can also generate TrueType and Type 1 fonts, although refined typographic control is better suited to a more specific application. Some other features of CorelDRAW include the creation and execution of VBA macros, viewing of colour separations in print preview mode and integrated professional imposing options. Dia is a free and open-source diagramming and vector graphics editor available for Windows, Linux and other Unix-based computer operating systems. Dia has a modular design and several shape packages for flowcharting, network diagrams and circuit diagrams. Its design was inspired by Microsoft Visio, although it uses a Single Document Interface similar to other GNOME software (such as GIMP). DrawPlus, first built for the Windows platform in 1993, has matured into a full featured vector graphics editor for home and professional users. Also available as a feature-limited free 'starter edition': DrawPlus SE. DrawPlus developers, Serif Europe, have now ceased its development in order to focus on its successor, Affinity Designer. Edraw Max is a cross-platform diagram software and vector graphics editor available for Windows, Mac and Linux. It supports kinds of diagram types. It supports imports and exports SVG, PDF, HTML, Multiple page TIFF, Microsoft Visio and Microsoft PowerPoint. Embroidermodder is a free machine embroidery software tool that supports a variety of formats and allows the user to add custom modifications to their embroidery designs. Fatpaint is a free, light-weight, browser-based graphic design application with built-in vector drawing tools. It can be accessed through any browser with Flash 9 installed. Its integration with Zazzle makes it particularly suitable for people who want to create graphics for custom printed products such as T-shirts, mugs, iPhone cases, flyers and other promotional products. Figma is a collaborative web-based online vector graphics editor, used primarily for UX design and prototyping. GIMP, which works mainly with raster images, offers a limited set of features to create and record SVG files. It can also load and handle SVG files created with other software like Inkscape. Inkscape is a free and open-source vector editor with the primary native format being SVG. Inkscape is available for Linux, Windows, Mac OS X, and
Breakup Notifier
Breakup Notifier was a web application written by product developer and programmer Dan Loewenherz that enabled its registered users to track the relationship status of their Facebook friends. An email notification was sent to the user when one of their Facebook friends changed their relationship status. The app was one of the most viral Facebook app's at the time of its release. It was mentioned in a skit on The Jay Leno Show and news of its popularity was published in Time magazine, The New York Post, CNET, and The Globe and Mail. == Popularity and Facebook controversy == Breakup Notifier gathered 100,000 users in less than 24 hours of its launch and reached a user base of more than 3,000,000 in February 2011. Facebook then blocked the app. Loewenherz later created an app named Crush Notifier, which differs from the original app in that users can check if they have a mutual crush. Breakup Notifier was later unblocked by Facebook and monetized.
Comparison of user features of messaging platforms
Comparison of user features of messaging platforms refers to a comparison of all the various user features of various electronic instant messaging platforms. This includes a wide variety of resources; it includes standalone apps, platforms within websites, computer software, and various internal functions available on specific devices, such as iMessage for iPhones. This entry includes only the features and functions that shape the user experience for such apps. A comparison of the underlying system components, programming aspects, and other internal technical information, is outside the scope of this entry. == Overview and background == Instant messaging technology is a type of online chat that offers real-time text transmission over the Internet. A LAN messenger operates in a similar way over a local area network. Short messages are typically transmitted between two parties when each user chooses to complete a thought and select "send". Some IM applications can use push technology to provide real-time text, which transmits messages character by character, as they are composed. More advanced instant messaging can add file transfer, clickable hyperlinks, Voice over IP, or video chat. Non-IM types of chat include multicast transmission, usually referred to as "chat rooms", where participants might be anonymous or might be previously known to each other (for example collaborators on a project that is using chat to facilitate communication). Instant messaging systems tend to facilitate connections between specified known users (often using a contact list also known as a "buddy list" or "friend list"). Depending on the IM protocol, the technical architecture can be peer-to-peer (direct point-to-point transmission) or client-server (an Instant message service center retransmits messages from the sender to the communication device). By 2010, instant messaging over the Web was in sharp decline, in favor of messaging features on social networks. The most popular IM platforms were terminated, such as AIM which closed down and Windows Live Messenger which merged into Skype. Instant messaging has since seen a revival in popularity in the form of "messaging apps" (usually on mobile devices) which by 2014 had more users than social networks. As of 2010, social networking providers often offer IM abilities. Facebook Chat is a form of instant messaging, and Twitter can be thought of as a Web 2.0 instant messaging system. Similar server-side chat features are part of most dating websites, such as OkCupid or PlentyofFish. The spread of smartphones and similar devices in the late 2000s also caused increased competition with conventional instant messaging, by making text messaging services still more ubiquitous. Many instant messaging services offer video calling features, voice over IP and web conferencing services. Web conferencing services can integrate both video calling and instant messaging abilities. Some instant messaging companies are also offering desktop sharing, IP radio, and IPTV to the voice and video features. The term "Instant Messenger" is a service mark of Time Warner and may not be used in software not affiliated with AOL in the United States. For this reason, in April 2007, the instant messaging client formerly named Gaim (or gaim) announced that they would be renamed "Pidgin". In the 2010s, more people started to use messaging apps on modern computers and devices like WhatsApp, WeChat, Viber, Facebook Messenger, Telegram, Signal and Line rather than instant messaging on computers like AIM and Windows Live Messenger. For example, WhatsApp was founded in 2009, and Facebook acquired in 2014, by which time it already had half a billion users. === Concepts === ==== Backchannel ==== Backchannel is the practice of using networked computers to maintain a real-time online conversation alongside the primary group activity or live spoken remarks. The term was coined in the field of linguistics to describe listeners' behaviours during verbal communication. (See Backchannel (linguistics).) The term "backchannel" generally refers to online conversation about the conference topic or speaker. Occasionally backchannel provides audience members a chance to fact-check the presentation. First growing in popularity at technology conferences, backchannel is increasingly a factor in education where WiFi connections and laptop computers allow participants to use ordinary chat like IRC or AIM to actively communicate during presentation. More recent research include works where the backchannel is brought publicly visible, such as the ClassCommons, backchan.nl and Fragmented Social Mirror. Twitter is also widely used today by audiences to create backchannels during broadcasting of content or at conferences. For example, television drama, other forms of entertainment and magazine programs. This practice is often also called live tweeting. Many conferences nowadays also have a hashtag that can be used by the participants to share notes and experiences; furthermore such hashtags can be user generated. == Features == Various platforms and apps are distinguished by their strengths and features in regards to specific functions. === Group messaging === === Official channels === Some apps include a feature known as "official channels" which allows companies, especially news media outlets, publications, and other mass media companies, to offer an official channel, which users can join, and thereby receive regular updates, published articles, or news updates from companies or news outlets. Two apps which have a large amount of such channels available are Line and Telegram. === Video group calls === == Basic default platforms == Basic platforms which are common across entire categories of mobile devices, computers, or operating systems. === SMS === SMS (short message service) is a text messaging service component of most telephone, Internet, and mobile device systems. It uses standardized communication protocols to enable mobile devices to exchange short text messages. An intermediary service can facilitate a text-to-voice conversion to be sent to landlines. SMS, as used on modern devices, originated from radio telegraphy in radio memo pagers that used standardized phone protocols. These were defined in 1985 as part of the Global System for Mobile Communications (GSM) series of standards. The first test SMS message was sent on December 3, 1992, when Neil Papwort, a test engineer for Sema Group, used a personal computer to send "Merry Christmas" to the phone of colleague Richard Jarvis. It commercially rolled out to many cellular networks that decade. SMS became hugely popular worldwide as a way of text communication. By the end of 2010, SMS was the most widely used data application, with an estimated 3.5 billion active users, or about 80% of all mobile phone subscribers. The protocols allowed users to send and receive messages of up to 160 characters (when entirely alpha-numeric) to and from GSM mobiles. Although most SMS messages are sent from one mobile phone to another, support for the service has expanded to include other mobile technologies, such as ANSI CDMA networks and Digital AMPS. Mobile marketing, a type of direct marketing, uses SMS. According to a 2018 market research report the global SMS messaging business was estimated to be worth over US$100 billion, accounting for almost 50 percent of all the revenue generated by mobile messaging. A Flash SMS is a type of SMS that appears directly on the main screen without user interaction and is not automatically stored in the inbox. It can be useful in emergencies, such as a fire alarm or cases of confidentiality, as in delivering one-time passwords. ==== Threaded SMS format ==== Threaded SMS is a visual styling orientation of SMS message history that arranges messages to and from a contact in chronological order on a single screen. It was first invented by a developer working to implement the SMS client for the BlackBerry, who was looking to make use of the blank screen left below the message on a device with a larger screen capable of displaying far more than the usual 160 characters, and was inspired by threaded Reply conversations in email. Visually, this style of representation provides a back-and-forth chat-like history for each individual contact. Hierarchical-threading at the conversation-level (as typical in blogs and on-line messaging boards) is not widely supported by SMS messaging clients. This limitation is due to the fact that there is no session identifier or subject-line passed back and forth between sent and received messages in the header data (as specified by SMS protocol) from which the client device can properly thread an incoming message to a specific dialogue, or even to a specific message within a dialogue. Most smart phone text-messaging-clients are able to create some contextual threading of "group messages" which narrows the context of the thread around the common interests shared by
Three-factor learning
In neuroscience and machine learning, three-factor learning is the combination of Hebbian plasticity with a third modulatory factor to stabilise and enhance synaptic learning. This third factor can represent various signals such as reward, punishment, error, surprise, or novelty, often implemented through neuromodulators. == Description == Three-factor learning introduces the concept of eligibility traces, which flag synapses for potential modification pending the arrival of the third factor, and helps temporal credit assignement by bridging the gap between rapid neuronal firing and slower behavioral timescales, from which learning can be done. Biological basis for Three-factor learning rules have been supported by experimental evidence. This approach addresses the instability of classical Hebbian learning by minimizing autocorrelation and maximizing cross-correlation between inputs.
Single particle analysis
Single particle analysis is a group of related computerized image processing techniques used to analyze images from transmission electron microscopy (TEM). These methods were developed to improve and extend the information obtainable from TEM images of particulate samples, typically proteins or other large biological entities such as viruses. Individual images of stained or unstained particles are very noisy, making interpretation difficult. Combining several digitized images of similar particles together gives an image with stronger and more easily interpretable features. An extension of this technique uses single particle methods to build up a three-dimensional reconstruction of the particle. Using cryo-electron microscopy it has become possible to generate reconstructions with sub-nanometer, near-atomic resolution resolution first in the case of highly symmetric viruses, and now in smaller, asymmetric proteins as well. == Techniques == Single particle analysis can be done on both negatively stained and vitreous ice-embedded transmission electron cryomicroscopy (CryoTEM) samples. Single particle analysis methods are, in general, reliant on the sample being homogeneous, although techniques for dealing with conformational heterogeneity are being developed. Images (micrographs) are taken with an electron microscope using charged-coupled device (CCD) detectors coupled to a phosphorescent layer (in the past, they were instead collected on film and digitized using high-quality scanners). The image processing is carried out using specialized software programs, often run on multi-processor computer clusters. Depending on the sample or the desired results, various steps of two- or three-dimensional processing can be done. === Alignment and classification === Biological samples, and especially samples embedded in thin vitreous ice, are highly radiation sensitive, thus only low electron doses can be used to image the sample. This low dose, as well as variations in the metal stain used (if used) means images have high noise relative to the signal given by the particle being observed. By aligning several similar images to each other so they are in register and then averaging them, an image with higher signal-to-noise ratio can be obtained. As the noise is mostly randomly distributed and the underlying image features constant, by averaging the intensity of each pixel over several images only the constant features are reinforced. Typically, the optimal alignment (a translation and an in-plane rotation) to map one image onto another is calculated by cross-correlation. However, a micrograph often contains particles in multiple different orientations and/or conformations, and so to get more representative image averages, a method is required to group similar particle images together into multiple sets. This is normally carried out using one of several data analysis and image classification algorithms, such as multi-variate statistical analysis and hierarchical ascendant classification, or k-means clustering. Often data sets of tens of thousands of particle images are used, and to reach an optimal solution an iterative procedure of alignment and classification is used, whereby strong image averages produced by classification are used as reference images for a subsequent alignment of the whole data set. === Image filtering === Image filtering (band-pass filtering) is often used to reduce the influence of high and/or low spatial frequency information in the images, which can affect the results of the alignment and classification procedures. This is particularly useful in negative stain images. The algorithms make use of fast Fourier transforms (FFT), often employing Gaussian shaped soft-edged masks in reciprocal space to suppress certain frequency ranges. High-pass filters remove low spatial frequencies (such as ramp or gradient effects), leaving the higher frequencies intact. Low-pass filters remove high spatial frequency features and have a blurring effect on fine details. === Contrast transfer function === Due to the nature of image formation in the electron microscope, bright-field TEM images are obtained using significant underfocus. This, along with features inherent in the microscope's lens system, creates blurring of the collected images visible as a point spread function. The combined effects of the imaging conditions are known as the contrast transfer function (CTF), and can be approximated mathematically as a function in reciprocal space. Specialized image processing techniques such as phase flipping and amplitude correction / Wiener filtering can (at least partially) correct for the CTF, and allow high resolution reconstructions. === Three-dimensional reconstruction === Transmission electron microscopy images are projections of the object showing the distribution of density through the object, similar to medical X-rays. By making use of the projection-slice theorem a three-dimensional reconstruction of the object can be generated by combining many images (2D projections) of the object taken from a range of viewing angles. Proteins in vitreous ice ideally adopt a random distribution of orientations (or viewing angles), allowing a fairly isotropic reconstruction if a large number of particle images are used. This contrasts with electron tomography, where the viewing angles are limited due to the geometry of the sample/imaging set up, giving an anisotropic reconstruction. Filtered back projection is a commonly used method of generating 3D reconstructions in single particle analysis, although many alternative algorithms exist. Before a reconstruction can be made, the orientation of the object in each image needs to be estimated. Several methods have been developed to work out the relative Euler angles of each image. Some are based on common lines (common 1D projections and sinograms), others use iterative projection matching algorithms. The latter works by beginning with a simple, low resolution 3D starting model and compares the experimental images to projections of the model and creates a new 3D to bootstrap towards a solution. Methods are also available for making 3D reconstructions of helical samples (such as tobacco mosaic virus), taking advantage of the inherent helical symmetry. Both real space methods (treating sections of the helix as single particles) and reciprocal space methods (using diffraction patterns) can be used for these samples. === Tilt methods === The specimen stage of the microscope can be tilted (typically along a single axis), allowing the single particle technique known as random conical tilt. An area of the specimen is imaged at both zero and at high angle (~60-70 degrees) tilts, or in the case of the related method of orthogonal tilt reconstruction, +45 and −45 degrees. Pairs of particles corresponding to the same object at two different tilts (tilt pairs) are selected, and by following the parameters used in subsequent alignment and classification steps a three-dimensional reconstruction can be generated relatively easily. This is because the viewing angle (defined as three Euler angles) of each particle is known from the tilt geometry. 3D reconstructions from random conical tilt suffer from missing information resulting from a restricted range of orientations. Known as the missing cone (due to the shape in reciprocal space), this causes distortions in the 3D maps. However, the missing cone problem can often be overcome by combining several tilt reconstructions. Tilt methods are best suited to negatively stained samples, and can be used for particles that adsorb to the carbon support film in preferred orientations. The phenomenon known as charging or beam-induced movement makes collecting high-tilt images of samples in vitreous ice challenging. === Map visualization and fitting === Various software programs are available that allow viewing the 3D maps. These often enable the user to manually dock in protein coordinates (structures from X-ray crystallography, NMR, or a computational model such as one found in the AlphaFold Protein Structure Database) of subunits into the electron density. Several programs can also fit subunits computationally; as of the 2020s using these programs tend to produce better accuracy than manual docking because they can perform labor-intensive tasks such as: The scale of SPA-derived maps depends on knowing the pixel size (angstorms per pixel), which is not always accurate. Programs can automatically correct for this difference by using coordinate data or by using knowledge of chemical bonds. Many proteins are made up of several roughly rigid protein domains linked by flexible parts. Pre-existing coordinate data, whether experimental or computational, may not exactly match the inter-domain positioning of the cyro-EM map. Modern programs can automatically "chop" pre-existing coordinate data into individual domains and fit them in individually. For higher-resolution structures, it is pos