The Common Crawl Foundation (Common Crawl) is a nonprofit 501(c)(3) organization that crawls the web and freely provides its archives and datasets to the public. Common Crawl was founded by Gil Elbaz. The data had mostly been primarily used by researchers and some startups until the 2020s, when AI companies started training large language models using the data. In November 2025, an investigation by The Atlantic revealed that Common Crawl misled publishers when it claimed it respected paywalls in its scraping and it was not honoring requests from publishers to have their content removed from its databases. == History == Common Crawl was founded in 2007 in San Francisco. It began publishing its crawls in 2011. By 2013, sites like TinEye were building their products off of Common Crawl. The crawl reduces the reliance of companies and researchers on Google, which has the biggest dataset. Common Crawl was designed to have more and fresher data that was more efficient to analyze and utilize than the Wayback Machine created by the Internet Archive. By 2015, 1.8 billion webpages were on the Common Crawl, which started by crawling a list of URLs donated by the search engine Blekko. They use Amazon Web Services, which provides some of its services for free, allowing computing costs to average $2-4000/month. The Common Crawl website listed 30 studies based on Common Crawl data. Before 2023, Common Crawl was not very well known outside of academic researchers who utilize the data. Common Crawl received its first requests to redact information in 2023 and increasingly started seeing its crawler, CCBot, blocked. In 2023, it began receiving significant financial support from AI companies, including Anthropic and OpenAI, each of which donated $250,000. It was also used to train Google DeepMind's large language model Gemini. By April 2023, Common Crawl was capturing 3.1 billion webpages, with an estimated 5% of pages before 2021 containing hate speech or slurs. As of 2024, Common Crawl had been cited in more than 10,000 academic studies. By 2024, The Pile and Common Crawl had been the two main training datasets being used to train AI models. In November 2025, an investigation by technology journalist Alex Reisner for The Atlantic revealed that Common Crawl misled publishers when it claimed it respected paywalls in its scraping and when it said that it was honoring requests from publishers to have their content removed from its databases. It included misleading results in the public search function on its website that showed no entries for websites that had requested their archives be removed, when in fact those sites were still included in its scrapes used by AI companies. As of 2025, Reisner found that CCBot was the most widely-blocked bot by the top 1000 websites. A 2026 article in LWN.net discussed an advantage to services like Common Crawl being that it can limit the scraping costs to websites by allowing companies and researchers to download the data from Common Crawl instead of scraping it themselves. In April 2026, Common Crawl experimentally began to distribute its data through Hugging Face Storage Bucket, in addition to its standard storage on Amazon S3. == Organization == Peter Norvig and Joi Ito have served on the advisory board. Rich Skrenta is the executive director. It has received funding almost exclusively from the Elbaz Family Foundation Trust until 2023 when it started receiving donations from the AI industry. == Refined versions == A number of organizations take raw Common Crawl data and refine it into datasets that exclude edgy content or are otherwise higher-quality for their purposes, such as FineWeb, DCLM and C4. === Colossal Clean Crawled Corpus === Google version of the Common Crawl is called the Colossal Clean Crawled Corpus, or C4 for short. It was constructed for the training of the T5 language model series in 2019. As of 2023, there were some concerns over copyrighted content in the C4 as well as racist content. A 2024 study found that 45% of content was explicitly restricted by websites' terms of service to be used for purposes like AI training by for-profit companies.
AIOps
AIOps (Artificial Intelligence for IT Operations) refers to the use of artificial intelligence, machine learning, and big data analytics to automate and enhance data center management. It helps organizations manage complex IT environments by detecting, diagnosing, and resolving issues more efficiently than traditional methods. == History == AIOps was first defined by Gartner in 2016, combining "artificial intelligence" and "IT operations" to describe the application of AI and machine learning to enhance IT operations. This concept was introduced to address the increasing complexity and data volume in IT environments, aiming to automate processes such as event correlation, anomaly detection, and causality determination. == Definition == AIOps refers to multi-layered, complex technology platforms that enhance and automate IT operations by using machine learning and analytics to analyze the large amounts of data collected from various DevOps devices and tools, automatically identifying and responding to issues in real-time. AIOps represents a shift from isolated IT data to aggregated observational data (e.g., job logs and monitoring systems) and interaction data (such as ticketing, events, or incident records) within a big data platform. AIOps applies machine learning and analytics to this data, resulting in continuous visibility that, when combined with automation, can lead to ongoing improvements. AIOps connects three IT disciplines (automation, service management, and performance management) to achieve continuous visibility and improvement. This new approach in modern, accelerated, and hyper-scaled IT environments leverages advances in machine learning and big data to overcome previous limitations. == Components == AIOps includes, but is not limited to, the following processes and techniques: Anomaly Detection Log Analysis Root Cause Analysis Cohort Analysis Event Correlation Predictive Analytics Hardware Failure Prediction Automated Remediation Performance Prediction Incident Management Causality Determination Queue Management Resource Scheduling and Optimization Predictive Capacity Management Resource Allocation Service Quality Monitoring Deployment and Integration Testing System Configuration Auto-diagnosis and Problem Localization Efficient ML Training and Inferencing Using LLMs for Cloud Ops Auto Service Healing Data Center Management Customer Support Security and Privacy in Cloud Operations == Comparison with DevOps == AIOps is increasingly compared with DevOps in terms of impact on operational efficiency. While DevOps focuses on collaboration between development and operations teams to accelerate software delivery, AIOps integrates artificial intelligence to enhance monitoring, automation, and predictive capabilities. Various industry analyses have explored the similarities and differences between the two approaches, including discussions on how organizations can combine them to improve incident management and resource optimization. == Results == AI optimizes IT operations in five ways: First, intelligent monitoring powered by AI helps identify potential issues before they cause outages, improving metrics like Mean Time to Detect (MTTD) by 15-20%. Second, performance data analysis and insights enable quick decision-making by ingesting and analyzing large data sets in real time. Third, AI-driven automated infrastructure optimization efficiently allocates resources and thereby reducing cloud costs. Fourth, enhanced IT service management reduces critical incidents by over 50% through AI-driven end-to-end service management. Lastly, intelligent task automation accelerates problem resolution and automates remedial actions with minimal human intervention. In 2025, Atera Networks was identified as a leader in AIOps by the software review platform G2. == AIOps vs. MLOps == AIOps tools use big data analytics, machine learning algorithms, and predictive analytics to detect anomalies, correlate events, and provide proactive insights. This automation reduces the burden on IT teams, allowing them to focus on strategic tasks rather than routine operational issues. AIOps is widely used by IT operations teams, DevOps, network administrators, and IT service management (ITSM) teams to enhance visibility and enable quicker incident resolution in hybrid cloud environments, data centers, and other IT infrastructures. In contrast to MLOps (Machine Learning Operations), which focuses on the lifecycle management and operational aspects of machine learning models, AIOps focuses on optimizing IT operations using a variety of analytics and AI-driven techniques. While both disciplines rely on AI and data-driven methods, AIOps primarily targets IT operations, whereas MLOps is concerned with the deployment, monitoring, and maintenance of ML models. == Conferences == There are several conferences that are specific to AIOps: AIOps Summit AI Dev Summit IBM Think conference
DONE
The Data-based Online Nonlinear Extremumseeker (DONE) algorithm is a black-box optimization algorithm. DONE models the unknown cost function and attempts to find an optimum of the underlying function. The DONE algorithm is suitable for optimizing costly and noisy functions and does not require derivatives. An advantage of DONE over similar algorithms, such as Bayesian optimization, is that the computational cost per iteration is independent of the number of function evaluations. == Methods == The DONE algorithm was first proposed by Hans Verstraete and Sander Wahls in 2015. The algorithm fits a surrogate model based on random Fourier features and then uses a well-known L-BFGS algorithm to find an optimum of the surrogate model. == Applications == DONE was first demonstrated for maximizing the signal in optical coherence tomography measurements, but has since then been applied to various other applications. For example, it was used to help extending the field of view in light sheet fluorescence microscopy.
Geospatial metadata
Geospatial metadata (also geographic metadata) is a type of metadata applicable to geographic data and information. Such objects may be stored in a geographic information system (GIS) or may simply be documents, data-sets, images or other objects, services, or related items that exist in some other native environment but whose features may be appropriate to describe in a (geographic) metadata catalog (may also be known as a data directory or data inventory). == Definition == ISO 19115:2013 "Geographic Information – Metadata" from ISO/TC 211, the industry standard for geospatial metadata, describes its scope as follows: [This standard] provides information about the identification, the extent, the quality, the spatial and temporal aspects, the content, the spatial reference, the portrayal, distribution, and other properties of digital geographic data and services. ISO 19115:2013 also provides for non-digital mediums: Though this part of ISO 19115 is applicable to digital data and services, its principles can be extended to many other types of resources such as maps, charts, and textual documents as well as non-geographic data. The U.S. Federal Geographic Data Committee (FGDC) describes geospatial metadata as follows: A metadata record is a file of information, usually presented as an XML document, which captures the basic characteristics of a data or information resource. It represents the who, what, when, where, why and how of the resource. Geospatial metadata commonly document geographic digital data such as Geographic Information System (GIS) files, geospatial databases, and earth imagery but can also be used to document geospatial resources including data catalogs, mapping applications, data models and related websites. Metadata records include core library catalog elements such as Title, Abstract, and Publication Data; geographic elements such as Geographic Extent and Projection Information; and database elements such as Attribute Label Definitions and Attribute Domain Values. == History == The growing appreciation of the value of geospatial metadata through the 1980s and 1990s led to the development of a number of initiatives to collect metadata according to a variety of formats either within agencies, communities of practice, or countries/groups of countries. For example, NASA's "DIF" metadata format was developed during an Earth Science and Applications Data Systems Workshop in 1987, and formally approved for adoption in 1988. Similarly, the U.S. FGDC developed its geospatial metadata standard over the period 1992–1994. The Spatial Information Council of Australia and New Zealand (ANZLIC), a combined body representing spatial data interests in Australia and New Zealand, released version 1 of its "metadata guidelines" in 1996. ISO/TC 211 undertook the task of harmonizing the range of formal and de facto standards over the approximate period 1999–2002, resulting in the release of ISO 19115 "Geographic Information – Metadata" in 2003 and a subsequent revision in 2013. As of 2011 individual countries, communities of practice, agencies, etc. have started re-casting their previously used metadata standards as "profiles" or recommended subsets of ISO 19115, occasionally with the inclusion of additional metadata elements as formal extensions to the ISO standard. The growth in popularity of Internet technologies and data formats, such as Extensible Markup Language (XML) during the 1990s led to the development of mechanisms for exchanging geographic metadata on the web. In 2004, the Open Geospatial Consortium released the current version (3.1) of Geography Markup Language (GML), an XML grammar for expressing geospatial features and corresponding metadata. With the growth of the Semantic Web in the 2000s, the geospatial community has begun to develop ontologies for representing semantic geospatial metadata. Some examples include the Hydrology and Administrative ontologies developed by the Ordnance Survey in the United Kingdom. == ISO 19115: Geographic information – Metadata == ISO 19115 is a standard of the International Organization for Standardization (ISO). The standard is part of the ISO geographic information suite of standards (19100 series). ISO 19115 and its parts define how to describe geographical information and associated services, including contents, spatial-temporal purchases, data quality, access and rights to use. The objective of this International Standard is to provide a clear procedure for the description of digital geographic data-sets so that users will be able to determine whether the data in a holding will be of use to them and how to access the data. By establishing a common set of metadata terminology, definitions and extension procedures, this standard promotes the proper use and effective retrieval of geographic data. ISO 19115 was revised in 2013 to accommodate growing use of the internet for metadata management, as well as add many new categories of metadata elements (referred to as codelists) and the ability to limit the extent of metadata use temporally or by user. == ISO 19139 Geographic information Metadata XML schema implementation == ISO 19139:2012 provides the XML implementation schema for ISO 19115 specifying the metadata record format and may be used to describe, validate, and exchange geospatial metadata prepared in XML. The standard is part of the ISO geographic information suite of standards (19100 series), and provides a spatial metadata XML (spatial metadata eXtensible Mark-up Language (smXML)) encoding, an XML schema implementation derived from ISO 19115, Geographic information – Metadata. The metadata includes information about the identification, constraint, extent, quality, spatial and temporal reference, distribution, lineage, and maintenance of the digital geographic data-set. == Metadata directories == Also known as metadata catalogues or data directories. (need discussion of, and subsections on GCMD, FGDC metadata gateway, ASDD, European and Canadian initiatives, etc. etc.) GIS Inventory – National GIS Inventory System which is maintained by the US-based National States Geographic Information Council (NSGIC) as a tool for the entire US GIS Community. Its primary purpose is to track data availability and the status of geographic information system (GIS) implementation in state and local governments to aid the planning and building of statewide spatial data infrastructures (SSDI). The Random Access Metadata for Online Nationwide Assessment (RAMONA) database is a critical component of the GIS Inventory. RAMONA moves its FGDC-compliant metadata (CSDGM Standard) for each data layer to a web folder and a Catalog Service for the Web (CSW) that can be harvested by Federal programs and others. This provides far greater opportunities for discovery of user information. The GIS Inventory website was originally created in 2006 by NSGIC under award NA04NOS4730011 from the Coastal Services Center, National Oceanic and Atmospheric Administration, U.S. Department of Commerce. The Department of Homeland Security has been the principal funding source since 2008 and they supported the development of the Version 5 during 2011/2012 under Order Number HSHQDC-11-P-00177. The Federal Emergency Management Agency and National Oceanic and Atmospheric Administration have provided additional resources to maintain and improve the GIS Inventory. Some US Federal programs require submission of CSDGM-Compliant Metadata for data created under grants and contracts that they issue. The GIS Inventory provides a very simple interface to create the required Metadata. GCMD - Global Change Master Directory's goal is to enable users to locate and obtain access to Earth science data sets and services relevant to global change and Earth science research. The GCMD database holds more than 20,000 descriptions of Earth science data sets and services covering all aspects of Earth and environmental sciences. ECHO - The EOS Clearing House (ECHO) is a spatial and temporal metadata registry, service registry, and order broker. It allows users to more efficiently search and access data and services through the Reverb Client or Application Programmer Interfaces (APIs). ECHO stores metadata from a variety of science disciplines and domains, totalling over 3400 Earth science data sets and over 118 million granule records. GoGeo - GoGeo is a service run by EDINA (University of Edinburgh) and is supported by Jisc. GoGeo allows users to conduct geographically targeted searches to discover geospatial datasets. GoGeo searches many data portals from the HE and FE community and beyond. GoGeo also allows users to create standards compliant metadata through its Geodoc metadata editor. == Geospatial metadata tools == There are many proprietary GIS or geospatial products that support metadata viewing and editing on GIS resources. For example, ESRI's ArcGIS Desktop, SOCET GXP, Autodesk's AutoCAD Map 3D 2008, Arcitecta's Mediaflux and Intergraph's Geo
Hindley–Milner type system
A Hindley–Milner (HM) type system is a classical type system for the lambda calculus with parametric polymorphism. It is also known as Damas–Milner or Damas–Hindley–Milner. It was first described by J. Roger Hindley and later rediscovered by Robin Milner. Luis Damas contributed a close formal analysis and proof of the method in his PhD thesis. Among HM's more notable properties are its completeness and its ability to infer the most general type of a given program without programmer-supplied type annotations or other hints. Algorithm W is an efficient type inference method in practice and has been successfully applied on large code bases, although it has a high theoretical complexity. HM is preferably used for functional programming languages. It was first implemented as part of the type system of the programming language ML. Since then, HM has been extended in various ways, most notably with type class constraints like those in Haskell. == Introduction == As a type inference method, Hindley–Milner is able to deduce the types of variables, expressions and functions from programs written in an entirely untyped style. Being scope sensitive, it is not limited to deriving the types only from a small portion of source code, but rather from complete programs or modules. Being able to cope with parametric types, too, it is core to the type systems of many functional programming languages. It was first applied in this manner in the ML programming language. The origin is the type inference algorithm for the simply typed lambda calculus that was devised by Haskell Curry and Robert Feys in 1958. In 1969, J. Roger Hindley extended this work and proved that their algorithm always inferred the most general type. In 1978, Robin Milner, independently of Hindley's work, provided an equivalent algorithm, Algorithm W. In 1982, Luis Damas finally proved that Milner's algorithm is complete and extended it to support systems with polymorphic references. === Monomorphism vs. polymorphism === In the simply typed lambda calculus, types T are either atomic type constants or function types of form T → T {\displaystyle T\rightarrow T} . Such types are monomorphic. Typical examples are the types used in arithmetic values: 3 : N u m b e r a d d 3 4 : N u m b e r a d d : N u m b e r → N u m b e r → N u m b e r {\displaystyle {\begin{array}{ll}3&:{\mathtt {Number}}\\{\mathtt {add}}\ 3\ 4&:{\mathtt {Number}}\\{\mathtt {add}}&:{\mathtt {Number}}\rightarrow {\mathtt {Number}}\rightarrow {\mathtt {Number}}\end{array}}} Contrary to this, the untyped lambda calculus is neutral to typing at all, and many of its functions can be meaningfully applied to all type of arguments. The trivial example is the identity function i d ≡ λ x . x {\displaystyle {\mathtt {id}}\equiv \lambda x.x} which simply returns whatever value it is applied to. Less trivial examples include parametric types like lists. While polymorphism in general means that operations accept values of more than one type, the polymorphism used here is parametric. One finds the notation of type schemes in the literature, too, emphasizing the parametric nature of the polymorphism. Additionally, constants may be typed with (quantified) type variables. For example, the following type schemes quantify universally over α {\displaystyle \alpha } , meaning that they are true for all possible α {\displaystyle \alpha } : c o n s : ∀ α . α → L i s t α → L i s t α n i l : ∀ α . L i s t α i d : ∀ α . α → α {\displaystyle {\begin{array}{ll}{\mathtt {cons}}&:\forall \alpha .\alpha \rightarrow {\mathtt {List}}\ \alpha \rightarrow {\mathtt {List}}\ \alpha \\{\mathtt {nil}}&:\forall \alpha .{\mathtt {List}}\ \alpha \\{\mathtt {id}}&:\forall \alpha .\alpha \rightarrow \alpha \end{array}}} Polymorphic types can become monomorphic by consistent substitution of their variables. Examples of monomorphic instances are: i d ′ : S t r i n g → S t r i n g n i l ′ : L i s t N u m b e r {\displaystyle {\begin{array}{ll}{\mathtt {id}}'&:{\mathtt {String}}\rightarrow {\mathtt {String}}\\{\mathtt {nil}}'&:{\mathtt {List}}\ {\mathtt {Number}}\end{array}}} More generally, types are polymorphic when they contain type variables, while types without them are monomorphic. Contrary to the type systems used for example in Pascal (1970) or C (1972), which only support monomorphic types, HM is designed with emphasis on parametric polymorphism. The successors of the languages mentioned, like C++ (1985), focused on different types of polymorphism, namely subtyping in connection with object-oriented programming and overloading. While subtyping is incompatible with HM, a variant of systematic overloading is available in the HM-based type system of Haskell. === Let-polymorphism === When extending the type inference for the simply-typed lambda calculus towards polymorphism, one has to decide whether assigning a polymorphic type not only as type of an expression, but also as the type of a λ-bound variable is admissible. This would allow the generic identity type to be assigned to the variable 'id' in: (λ id . ... (id 3) ... (id "text") ... ) (λ x . x) Allowing this gives rise to the polymorphic lambda calculus; however, type inference in this system is not decidable. Instead, HM distinguishes variables that are immediately bound to an expression from more general λ-bound variables, calling the former let-bound variables, and allows polymorphic types to be assigned only to these. This leads to let-polymorphism where the above example takes the form let id = λ x . x in ... (id 3) ... (id "text") ... which can be typed with a polymorphic type for 'id'. As indicated, the expression syntax is extended to make the let-bound variables explicit, and by restricting the type system to allow only let-bound variable to have polymorphic types, while the parameters in lambda-abstractions must get a monomorphic type, type inference becomes decidable. == Overview == The remainder of this article proceeds as follows: The HM type system is defined. This is done by describing a deduction system that makes precise what expressions have what type, if any. From there, it works towards an implementation of the type inference method. After introducing a syntax-driven variant of the above deductive system, it sketches an efficient implementation (algorithm J), appealing mostly to the reader's metalogical intuition. Because it remains open whether algorithm J indeed realises the initial deduction system, a less efficient implementation (algorithm W), is introduced and its use in a proof is hinted. Finally, further topics related to the algorithm are discussed. The same description of the deduction system is used throughout, even for the two algorithms, to make the various forms in which the HM method is presented directly comparable. == The Hindley–Milner type system == The type system can be formally described by syntax rules that fix a language for the expressions, types, etc. The presentation here of such a syntax is not too formal, in that it is written down not to study the surface grammar, but rather the depth grammar, and leaves some syntactical details open. This form of presentation is usual. Building on this, typing rules are used to define how expressions and types are related. As before, the form used is a bit liberal. === Syntax === The expressions to be typed are exactly those of the lambda calculus extended with a let-expression as shown in the adjacent table. Parentheses can be used to disambiguate an expression. The application is left-binding and binds stronger than abstraction or the let-in construct. Types are syntactically split into two groups, monotypes and polytypes. ==== Monotypes ==== Monotypes always designate a particular type. Monotypes τ {\displaystyle \tau } are syntactically represented as terms. Examples of monotypes include type constants like i n t {\displaystyle {\mathtt {int}}} or s t r i n g {\displaystyle {\mathtt {string}}} , and parametric types like M a p ( S e t s t r i n g ) i n t {\displaystyle {\mathtt {Map\ (Set\ string)\ int}}} . The latter types are examples of applications of type functions, for example, from the set { M a p 2 , S e t 1 , s t r i n g 0 , i n t 0 , → 2 } {\displaystyle \{{\mathtt {Map^{2},\ Set^{1},\ string^{0},\ int^{0}}},\ \rightarrow ^{2}\}} , where the superscript indicates the number of type parameters. The complete set of type functions C {\displaystyle C} is arbitrary in HM, except that it must contain at least → 2 {\displaystyle \rightarrow ^{2}} , the type of functions. It is often written in infix notation for convenience. For example, a function mapping integers to strings has type i n t → s t r i n g {\displaystyle {\mathtt {int}}\rightarrow {\mathtt {string}}} . Again, parentheses can be used to disambiguate a type expression. The application binds stronger than the infix arrow, which is right-binding. Type variables are admitted as monotypes. Monotypes are not to be confused with monomorphic types, which exc
Pill reminder
A pill reminder is any device that reminds users to take medications. Traditional pill reminders are pill containers with electric timers attached, which can be preset for certain times of the day to set off an alarm. More sophisticated pill reminders can also detect when they have been opened, and therefore when the user is away during the time they were supposed to take their medication, they will be reminded of it when they return. This reminder can be in the form of a light, which also helps for deaf or hearing-impaired users. == Mobile app == A newer type of pill reminder is a mobile app that reminds the owner to take the medication. Some of these applications might effectively support adherence to taking medications.
Cancer Likelihood in Plasma
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.