Cancer Likelihood in Plasma (CLiP) refers to a set of ensemble learning methods for integrating various genomic features useful for the noninvasive detection of early cancers from blood plasma. An application of this technique for early detection of lung cancer (Lung-CLiP) was originally described by Chabon et al. (2020) from the labs of Ash Alizadeh and Max Diehn at Stanford. This method relies on several improvements to cancer personalized profiling by deep sequencing (CAPP-Seq) for analysis of circulating tumor DNA (ctDNA). The CLiP technique integrates multiple distinctive genomic features of a cancer of interest findings within a machine-learning framework for cancer detection. For example, studies have shown that the majority of somatic mutations found in cell-free DNA (cfDNA) are not tumor derived, but instead reflect clonal hematopoeisis (also known as CHIP). Even though CHIP tends to target specific genes, it also involves many generally non-recurrent mutations that can be shed from leukocytes and detected in cfDNA, regardless of whether profiling patients with cancer and healthy adults. However, genuine tumor derived ctDNA mutations can be distinguished from CHIP-derived mutations. This is because unlike tumor-derived mutations, CHIP-derived mutations that are shed from leukocytes into plasma tend to occur on longer cfDNA fragments, and to lack specific mutational signatures such as those associated with tobacco smoking in lung cancer that are also found in tumor derived ctDNA molecules. CLiP integrates these features within hierarchical ensemble machine learning models that consider somatic mutations and copy number alternations, among other features. While the CLiP method is unique in relying exclusively on mutations and copy number alterations, it is related to a variety of other liquid biopsy methods being commercially developed for early cancer detection using ctDNA and proteins (e.g., CancerSEEK / DETECT-A ), cfDNA fragmentation patterns (e.g., DELFI), and DNA methylation (e.g., cfMeDIP-Seq, Grail). While the CLiP method has not yet been broadly applied for population-based cancer screening, it has been shown to distinguish discriminate early-stage lung cancers from risk-matched controls across multiple cohorts of patients enrolled across the US.
Perusall
Perusall is a social web annotation tool intended for use by students at schools and universities. It allows users to annotate the margins of a text in a virtual group setting that is similar to social media—with upvoting, emojis, chat functionality, and notification. It also includes automatic AI grading. == History == Perusall began as a research project at Harvard University. It later became an educational product for students and teachers. As of 2024, Perusall states more than 5 million students have used the tool at over 5,000 educational institutions in 112 countries." == Functionality == Perusall integrates with learning management systems such as Moodle, Canvas and Blackboard to aid with collaborative annotation. The tool supports annotation of a range of media including text, images, equations, videos, PDFs and snapshots of webpages.
Lex (software)
Lex is a computer program that generates lexical analyzers ("scanners" or "lexers"). It is commonly used with the yacc parser generator and is the standard lexical analyzer generator on many Unix and Unix-like systems. An equivalent tool is specified as part of the POSIX standard. Lex reads an input stream specifying the lexical analyzer and writes source code which implements the lexical analyzer in the C programming language. In addition to C, some old versions of Lex could generate a lexer in Ratfor. == History == Lex was originally written by Mike Lesk and Eric Schmidt and described in 1975. In the following years, Lex became the standard lexical analyzer generator on many Unix and Unix-like systems. In 1983, Lex was one of several UNIX tools available for Charles River Data Systems' UNOS operating system under the Bell Laboratories license. Although originally distributed as proprietary software, some versions of Lex are now open-source. Open-source versions of Lex, based on the original proprietary code, are now distributed with open-source operating systems such as OpenSolaris and Plan 9 from Bell Labs. One popular open-source version of Lex, called flex, or the "fast lexical analyzer", is not derived from proprietary coding. == Structure of a Lex file == The structure of a Lex file is intentionally similar to that of a yacc file: files are divided into three sections, separated by lines that contain only two percent signs, as follows: The definitions section defines macros and imports header files written in C. It is also possible to write any C code here, which will be copied verbatim into the generated source file. The rules section associates regular expression patterns with C statements. When the lexer sees text in the input matching a given pattern, it will execute the associated C code. The C code section contains C statements and functions that are copied verbatim to the generated source file. These statements presumably contain code called by the rules in the rules section. In large programs it is more convenient to place this code in a separate file linked in at compile time. == Example of a Lex file == The following is an example Lex file for the flex version of Lex. It recognizes strings of numbers (positive integers) in the input, and simply prints them out. If this input is given to flex, it will be converted into a C file, lex.yy.c. This can be compiled into an executable which matches and outputs strings of integers. For example, given the input: abc123z.!&2gj6 the program will print: Saw an integer: 123 Saw an integer: 2 Saw an integer: 6 == Using Lex with other programming tools == === Using Lex with parser generators === Lex, as with other lexical analyzers, limits rules to those which can be described by regular expressions. Due to this, Lex can be implemented by a finite-state automata as shown by the Chomsky hierarchy of languages. To recognize more complex languages, Lex is often used with parser generators such as Yacc or Bison. Parser generators use a formal grammar to parse an input stream. It is typically preferable to have a parser, one generated by Yacc for instance, accept a stream of tokens (a "token-stream") as input, rather than having to process a stream of characters (a "character-stream") directly. Lex is often used to produce such a token-stream. Scannerless parsing refers to parsing the input character-stream directly, without a distinct lexer. === Lex and make === make is a utility that can be used to maintain programs involving Lex. Make assumes that a file that has an extension of .l is a Lex source file. The make internal macro LFLAGS can be used to specify Lex options to be invoked automatically by make.
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Kalman filter
In statistics and control theory, Kalman filtering (also known as linear quadratic estimation) is an algorithm that uses a series of measurements observed over time, including statistical noise and other inaccuracies, to produce estimates of unknown variables that tend to be more accurate than those based on a single measurement, by estimating a joint probability distribution over the variables for each time-step. The filter is constructed as a mean squared error minimiser, but an alternative derivation of the filter is also provided showing how the filter relates to maximum likelihood statistics. The filter is named after Rudolf E. Kálmán. Kalman filtering has numerous technological applications. A common application is for guidance, navigation, and control of vehicles, particularly aircraft, spacecraft and ships positioned dynamically. Furthermore, Kalman filtering is much applied in time series analysis tasks such as signal processing and econometrics. Kalman filtering is also important for robotic motion planning and control, and can be used for trajectory optimization. Kalman filtering also works for modeling the central nervous system's control of movement. Due to the time delay between issuing motor commands and receiving sensory feedback, the use of Kalman filters provides a realistic model for making estimates of the current state of a motor system and issuing updated commands. The algorithm works via a two-phase process: a prediction phase and an update phase. In the prediction phase, the Kalman filter produces estimates of the current state variables, including their uncertainties. Once the outcome of the next measurement (necessarily corrupted with some error, including random noise) is observed, these estimates are updated using a weighted average, with more weight given to estimates with greater certainty. The algorithm is recursive. It can operate in real time, using only the present input measurements and the state calculated previously and its uncertainty matrix; no additional past information is required. Optimality of Kalman filtering assumes that errors have a normal (Gaussian) distribution. In the words of Rudolf E. Kálmán, "The following assumptions are made about random processes: Physical random phenomena may be thought of as due to primary random sources exciting dynamic systems. The primary sources are assumed to be independent gaussian random processes with zero mean; the dynamic systems will be linear." Regardless of Gaussianity, however, if the process and measurement covariances are known, then the Kalman filter is the best possible linear estimator in the minimum mean-square-error sense, although there may be better nonlinear estimators. It is a common misconception (perpetuated in the literature) that the Kalman filter cannot be rigorously applied unless all noise processes are assumed to be Gaussian. Extensions and generalizations of the method have also been developed, such as the extended Kalman filter and the unscented Kalman filter which work on nonlinear systems. The basis is a hidden Markov model such that the state space of the latent variables is continuous and all latent and observed variables have Gaussian distributions. Kalman filtering has been used successfully in multi-sensor fusion, and distributed sensor networks to develop distributed or consensus Kalman filtering. == History == The filtering method is named for Hungarian émigré Rudolf E. Kálmán, although Thorvald Nicolai Thiele and Peter Swerling developed a similar algorithm earlier. Richard S. Bucy of the Johns Hopkins Applied Physics Laboratory contributed to the theory, causing it to be known sometimes as Kalman–Bucy filtering. Kalman was inspired to derive the Kalman filter by applying state variables to the Wiener filtering problem. Stanley F. Schmidt is generally credited with developing the first implementation of a Kalman filter. He realized that the filter could be divided into two distinct parts, with one part for time periods between sensor outputs and another part for incorporating measurements. It was during a visit by Kálmán to the NASA Ames Research Center that Schmidt saw the applicability of Kálmán's ideas to the nonlinear problem of trajectory estimation for the Apollo program resulting in its incorporation in the Apollo navigation computer. This digital filter is sometimes termed the Stratonovich–Kalman–Bucy filter because it is a special case of a more general, nonlinear filter developed by the Soviet mathematician Ruslan Stratonovich. In fact, some of the special case linear filter's equations appeared in papers by Stratonovich that were published before the summer of 1961, when Kalman met with Stratonovich during a conference in Moscow. This Kalman filtering was first described and developed partially in technical papers by Swerling (1958), Kalman (1960) and Kalman and Bucy (1961). The Apollo computer used 2k of magnetic core RAM and 36k wire rope [...]. The CPU was built from ICs [...]. Clock speed was under 100 kHz [...]. The fact that the MIT engineers were able to pack such good software (one of the very first applications of the Kalman filter) into such a tiny computer is truly remarkable. Kalman filters have been vital in the implementation of the navigation systems of U.S. Navy nuclear ballistic missile submarines, and in the guidance and navigation systems of cruise missiles such as the U.S. Navy's Tomahawk missile and the U.S. Air Force's Air Launched Cruise Missile. They are also used in the guidance and navigation systems of reusable launch vehicles and the attitude control and navigation systems of spacecraft which dock at the International Space Station. == Overview of the calculation == Kalman filtering uses a system's dynamic model (e.g., physical laws of motion), known control inputs to that system, and multiple sequential measurements (such as from sensors) to form an estimate of the system's varying quantities (its state) that is better than the estimate obtained by using only one measurement alone. As such, it is a common sensor fusion and data fusion algorithm. Noisy sensor data, approximations in the equations that describe the system evolution, and external factors that are not accounted for, all limit how well it is possible to determine the system's state. The Kalman filter deals effectively with the uncertainty due to noisy sensor data and, to some extent, with random external factors. The Kalman filter produces an estimate of the state of the system as an average of the system's predicted state and of the new measurement using a weighted average. The purpose of the weights is that values with better (i.e., smaller) estimated uncertainty are "trusted" more. The weights are calculated from the covariance, a measure of the estimated uncertainty of the prediction of the system's state. The result of the weighted average is a new state estimate that lies between the predicted and measured state, and has a better estimated uncertainty than either alone. This process is repeated at every time step, with the new estimate and its covariance informing the prediction used in the following iteration. This means that Kalman filter works recursively and requires only the last "best guess", rather than the entire history, of a system's state to calculate a new state. The measurements' certainty-grading and current-state estimate are important considerations. It is common to discuss the filter's response in terms of the Kalman filter's gain. The Kalman gain is the weight given to the measurements and current-state estimate, and can be "tuned" to achieve a particular performance. With a high gain, the filter places more weight on the most recent measurements, and thus conforms to them more responsively. With a low gain, the filter conforms to the model predictions more closely. At the extremes, a high gain (close to one) will result in a more jumpy estimated trajectory, while a low gain (close to zero) will smooth out noise but decrease the responsiveness. When performing the actual calculations for the filter (as discussed below), the state estimate and covariances are coded into matrices because of the multiple dimensions involved in a single set of calculations. This allows for a representation of linear relationships between different state variables (such as position, velocity, and acceleration) in any of the transition models or covariances. == Example application == As an example application, consider the problem of determining the precise location of a truck. The truck can be equipped with a GPS unit that provides an estimate of the position within a few meters. The GPS estimate is likely to be noisy; readings 'jump around' rapidly, though remaining within a few meters of the real position. In addition, since the truck is expected to follow the laws of physics, its position can also be estimated by integrating its velocity over time, determined by keeping track of wheel revolutions and the
Pixel aspect ratio
A pixel aspect ratio (PAR) is a mathematical ratio that describes how the width of a pixel in a digital image compares to the height of that pixel. Most digital imaging systems display an image as a grid of tiny, square pixels. However, some imaging systems, especially those that must be compatible with standard-definition television motion pictures, display an image as a grid of rectangular pixels, in which the pixel width and height are different. Pixel aspect ratio describes this difference. Use of pixel aspect ratio mostly involves pictures pertaining to standard-definition television and some other exceptional cases. Most other imaging systems, including those that comply with SMPTE standards and practices, use square pixels. PAR is also known as sample aspect ratio and abbreviated SAR, though it can be confused with storage aspect ratio. == Introduction == The ratio of the width to the height of an image is known as the aspect ratio, or more precisely the display aspect ratio (DAR) – the aspect ratio of the image as displayed; for TV, DAR was traditionally 4:3 (a.k.a. fullscreen), with 16:9 (a.k.a. widescreen) now the standard for HDTV. In digital images, there is a distinction with the storage aspect ratio (SAR), which is the ratio of pixel dimensions. If an image is displayed with square pixels, then these ratios agree; if not, then non-square, "rectangular" pixels are used, and these ratios disagree. The aspect ratio of the pixels themselves is known as the pixel aspect ratio (PAR) – for square pixels this is 1:1 – and these are related by the identity: Rearranging (solving for PAR) yields: For example: A 640 × 480 VGA image has a SAR of 640/480 = 4:3, and if displayed on a 4:3 display (DAR = 4:3) has square pixels, hence a PAR of 1:1. By contrast, a 720 × 576 D-1 PAL image has a SAR of 720/576 = 5:4, but if displayed on a 4:3 display (DAR = 4:3) the PAR is 4/3 : 5/4 = 16:15 ≈ 1.066. This means that the pixels of the PAL picture must be "stretched" by this amount to fit in the 4:3 display. In analog images such as film there is no notion of pixel, nor notion of SAR or PAR, but in the digitization of analog images the resulting digital image has pixels, hence SAR (and accordingly PAR, if displayed at the same aspect ratio as the original). Non-square pixels arise often in early digital TV standards, related to digitalization of analog TV signals – whose vertical and "effective" horizontal resolutions differ and are thus best described by non-square pixels – and also in some digital video cameras and computer display modes, such as Color Graphics Adapter (CGA). Today they arise also in transcoding between resolutions with different SARs. Actual displays do not generally have non-square pixels, though digital sensors might; they are rather a mathematical abstraction used in resampling images to convert between resolutions. There are several complicating factors in understanding PAR, particularly as it pertains to digitization of analog video: First, analog video does not have pixels, but rather a raster scan, and thus has a well-defined vertical resolution (the lines of the raster), but not a well-defined horizontal resolution, since each line is an analog signal. However, by a standardized sampling rate, the effective horizontal resolution can be determined by the sampling theorem, as is done below. Second, due to overscan, some of the lines at the top and bottom of the raster are not visible, as are some of the possible image on the left and right – see Overscan: Analog to digital resolution issues. Also, the resolution may be rounded (DV NTSC uses 480 lines, rather than the 486 that are possible). Third, analog video signals are interlaced – each image (frame) is sent as two "fields", each with half the lines. Thus either the pixels are twice as tall as they would be without interlacing, or the image is deinterlaced. == Background == Video is presented as a sequential series of images called video frames. Historically, video frames were created and recorded in analog form. As digital display technology, digital broadcast technology, and digital video compression evolved separately, it resulted in video frame differences that must be addressed using pixel aspect ratio. Digital video frames are generally defined as a grid of pixels used to present each sequential image. The horizontal component is defined by pixels (or samples), and is known as a video line. The vertical component is defined by the number of lines, as in 480 lines. Standard-definition television standards and practices were developed as broadcast technologies and intended for terrestrial broadcasting, and were therefore not designed for digital video presentation. Such standards define an image as an array of well-defined horizontal "Lines", well-defined vertical "Line Duration" and a well-defined picture center. However, there is not a standard-definition television standard that properly defines image edges or explicitly demands a certain number of picture elements per line. Furthermore, analog video systems such as NTSC 480i and PAL 576i, instead of employing progressively displayed frames, employ fields or interlaced half-frames displayed in an interwoven manner to reduce flicker and double the image rate for smoother motion. === Analog-to-digital conversion === As a result of computers becoming powerful enough to serve as video editing tools, video digital-to-analog converters and analog-to-digital converters were made to overcome this incompatibility. To convert analog video lines into a series of square pixels, the industry adopted a default sampling rate at which luma values were extracted into pixels. The luma sampling rate for 480i pictures was 12+3⁄11 MHz and for 576i pictures was 14+3⁄4 MHz. The term pixel aspect ratio was first coined when ITU-R BT.601 (commonly known as Rec. 601) specified that standard-definition television pictures are made of lines of exactly 720 non-square pixels. ITU-R BT.601 did not define the exact pixel aspect ratio but did provide enough information to calculate the exact pixel aspect ratio based on industry practices: The standard luma sampling rate of precisely 13+1⁄2 MHz. Based on this information: The pixel aspect ratio for 480i would be 10:11 as: 12 3 11 ÷ 13 1 2 = 10 11 {\displaystyle 12{\tfrac {3}{11}}\div 13{\tfrac {1}{2}}={\tfrac {10}{11}}} The pixel aspect ratio for 576i would be 59:54 as: 14 3 4 ÷ 13 1 2 = 59 54 {\displaystyle 14{\tfrac {3}{4}}\div 13{\tfrac {1}{2}}={\tfrac {59}{54}}} SMPTE RP 187 further attempted to standardize the pixel aspect ratio values for 480i and 576i. It designated 177:160 for 480i or 1035:1132 for 576i. However, due to significant difference with practices in effect by industry and the computational load that they imposed upon the involved hardware, SMPTE RP 187 was simply ignored. SMPTE RP 187 information annex A.4 further suggested the use of 10:11 for 480i. As of this writing, ITU-R BT.601-6, which is the latest edition of ITU-R BT.601, still implies that the pixel aspect ratios mentioned above are correct. === Digital video processing === As stated above, ITU-R BT.601 specified that standard-definition television pictures are made of lines of 720 non-square pixels, sampled with a precisely specified sampling rate. A simple mathematical calculation reveals that a 704 pixel width would be enough to contain a 480i or 576i standard 4:3 picture: A 4:3 480-line picture, digitized with the Rec. 601-recommended sampling rate, would be 704 non-square pixels wide. x 480 × 10 11 = 4 3 ⇒ x = 480 × 11 × 4 10 × 3 = 704 {\displaystyle {\frac {x}{480}}\times {\frac {10}{11}}={\frac {4}{3}}\Rightarrow x={\frac {480\times 11\times 4}{10\times 3}}=704} A 4:3 576-line picture, digitized with the Rec. 601-recommended sampling rate, would be 702+54⁄59 non-square pixels wide. x 576 × 59 54 = 4 3 ⇒ x = 576 × 54 × 4 59 × 3 = 702 54 59 {\displaystyle {\frac {x}{576}}\times {\frac {59}{54}}={\frac {4}{3}}\Rightarrow x={\frac {576\times 54\times 4}{59\times 3}}=702{\tfrac {54}{59}}} Unfortunately, not all standard TV pictures are exactly 4:3: As mentioned earlier, in analog video, the center of a picture is well-defined but the edges of the picture are not standardized. As a result, some analog devices (mostly PAL devices but also some NTSC devices) generated motion pictures that were horizontally (slightly) wider. This also proportionately applies to anamorphic widescreen (16:9) pictures. Therefore, to maintain a safe margin of error, ITU-R BT.601 required sampling 16 more non-square pixels per line (8 more at each edge) to ensure saving all video data near the margins. This requirement, however, had implications for PAL motion pictures. PAL pixel aspect ratios for standard (4:3) and anamorphic wide screen (16:9), respectively 59:54 and 118:81, were awkward for digital image processing, especially for mixing PAL and NTSC video clips. Therefore, video editing products chose the almost equivalent value
JOONE
JOONE (Java Object Oriented Neural Engine) is a component based neural network framework built in Java. == Features == Joone consists of a component-based architecture based on linkable components that can be extended to build new learning algorithms and neural networks architectures. Components are plug-in code modules that are linked to produce an information flow. New components can be added and reused. Beyond simulation, Joone also has to some extent multi-platform deployment capabilities. Joone has a GUI Editor to graphically create and test any neural network, and a distributed training environment that allows for neural networks to be trained on multiple remote machines. == Comparison == As of 2010, Joone, Encog and Neuroph are the major free component based neural network development environment available for the Java platform. Unlike the two other (commercial) systems that are in existence, Synapse and NeuroSolutions, it is written in Java and has direct cross-platform support. A limited number of components exist and the graphical development environment is rudimentary so it has significantly fewer features than its commercial counterparts. Joone can be considered to be more of a neural network framework than a full integrated development environment. Unlike its commercial counterparts, it has a strong focus on code-based development of neural networks rather than visual construction. While in theory Joone can be used to construct a wider array of adaptive systems (including those with non-adaptive elements), its focus is on backpropagation based neural networks.