Super-resolution optical fluctuation imaging

Super-resolution optical fluctuation imaging

Super-resolution optical fluctuation imaging (SOFI) is a post-processing method for the calculation of super-resolved images from recorded image time series that is based on the temporal correlations of independently fluctuating fluorescent emitters. SOFI has been developed for super-resolution of biological specimen that are labelled with independently fluctuating fluorescent emitters (organic dyes, fluorescent proteins). In comparison to other super-resolution microscopy techniques such as STORM or PALM that rely on single-molecule localization and hence only allow one active molecule per diffraction-limited area (DLA) and timepoint, SOFI does not necessitate a controlled photoswitching and/ or photoactivation as well as long imaging times. Nevertheless, it still requires fluorophores that are cycling through two distinguishable states, either real on-/off-states or states with different fluorescence intensities. In mathematical terms SOFI-imaging relies on the calculation of cumulants, for what two distinguishable ways exist. For one thing an image can be calculated via auto-cumulants that by definition only rely on the information of each pixel itself, and for another thing an improved method utilizes the information of different pixels via the calculation of cross-cumulants. Both methods can increase the final image resolution significantly although the cumulant calculation has its limitations. Actually SOFI is able to increase the resolution in all three dimensions. == Principle == Likewise to other super-resolution methods SOFI is based on recording an image time series on a CCD- or CMOS camera. In contrary to other methods the recorded time series can be substantially shorter, since a precise localization of emitters is not required and therefore a larger quantity of activated fluorophores per diffraction-limited area is allowed. The pixel values of a SOFI-image of the n-th order are calculated from the values of the pixel time series in the form of a n-th order cumulant, whereas the final value assigned to a pixel can be imagined as the integral over a correlation function. The finally assigned pixel value intensities are a measure of the brightness and correlation of the fluorescence signal. Mathematically, the n-th order cumulant is related to the n-th order correlation function, but exhibits some advantages concerning the resulting resolution of the image. Since in SOFI several emitters per DLA are allowed, the photon count at each pixel results from the superposition of the signals of all activated nearby emitters. The cumulant calculation now filters the signal and leaves only highly correlated fluctuations. This provides a contrast enhancement and therefore a background reduction for good measure. As it is implied in the figure on the left the fluorescence source distribution: ∑ k = 1 N δ ( r → − r → k ) ⋅ ε k ⋅ s k ( t ) {\displaystyle \sum _{k=1}^{N}\delta ({\vec {r}}-{\vec {r}}_{k})\cdot \varepsilon _{k}\cdot s_{k}(t)} is convolved with the system's point spread function (PSF) U(r). Hence the fluorescence signal at time t and position r → {\displaystyle {\vec {r}}} is given by F ( r → , t ) = ∑ k = 1 N U ( r → − r → k ) ⋅ ε k ⋅ s k ( t ) . {\displaystyle F({\vec {r}},t)=\sum _{k=1}^{N}U({\vec {r}}-{\vec {r}}_{k})\cdot \varepsilon _{k}\cdot s_{k}(t).} Within the above equations N is the amount of emitters, located at the positions r → k {\displaystyle {\vec {r}}_{k}} with a time-dependent molecular brightness ε k ⋅ s k {\displaystyle \varepsilon _{k}\cdot s_{k}} where ε k {\displaystyle \varepsilon _{k}} is a variable for the constant molecular brightness and s k ( t ) {\displaystyle s_{k}(t)} is a time-dependent fluctuation function. The molecular brightness is just the average fluorescence count-rate divided by the number of molecules within a specific region. For simplification it has to be assumed that the sample is in a stationary equilibrium and therefore the fluorescence signal can be expressed as a zero-mean fluctuation: δ F ( r → , t ) = F ( r → , t ) − ⟨ F ( r → , t ) ⟩ t {\displaystyle \delta F({\vec {r}},t)=F({\vec {r}},t)-\langle F({\vec {r}},t)\rangle _{t}} where ⟨ ⋯ ⟩ t {\displaystyle \langle \cdots \rangle _{t}} denotes time-averaging. The auto-correlation here e.g. the second-order can then be described deductively as follows for a certain time-lag τ {\displaystyle \tau } : δ F ( r → , t ) = ⟨ δ F ( r → , t + τ ) ⋅ δ F ( r → , t ) ⟩ t {\displaystyle \delta F({\vec {r}},t)=\langle \delta F({\vec {r}},t+\tau )\cdot \delta F({\vec {r}},t)\rangle _{t}} From these equations it follows that the PSF of the optical system has to be taken to the power of the order of the correlation. Thus in a second-order correlation the PSF would be reduced along all dimensions by a factor of 2 {\displaystyle {\sqrt {2}}} . As a result, the resolution of the SOFI-images increases according to this factor. === Cumulants versus correlations === Using only the simple correlation function for a reassignment of pixel values, would ascribe to the independency of fluctuations of the emitters in time in a way that no cross-correlation terms would contribute to the new pixel value. Calculations of higher-order correlation functions would suffer from lower-order correlations for what reason it is superior to calculate cumulants, since all lower-order correlation terms vanish. == Cumulant-calculation == === Auto-cumulants === For computational reasons it is convenient to set all time-lags in higher-order cumulants to zero so that a general expression for the n-th order auto-cumulant can be found: A C n ( r → , τ 1 … n − 1 = 0 ) = ∑ k = 1 N U n ( r → − r → k ) ε k n w k ( 0 ) {\displaystyle AC_{n}({\vec {r}},\tau _{1\ldots n-1}=0)=\sum _{k=1}^{N}U^{n}({\vec {r}}-{\vec {r}}_{k})\varepsilon _{k}^{n}w_{k}(0)} w k {\displaystyle w_{k}} is a specific correlation based weighting function influenced by the order of the cumulant and mainly depending on the fluctuation properties of the emitters. Albeit there is no fundamental limitation in calculating very high orders of cumulants and thereby shrinking the FWHM of the PSF there are practical limitations according to the weighting of the values assigned to the final image. Emitters with a higher molecular brightness will show a strong increase in terms of the pixel cumulant value assigned at higher-orders as well as this performance can be expected from a diverse appearance of fluctuations of different emitters. A wide intensity range of the resulting image can therefore be expected and as a result dim emitters can get masked by bright emitters in higher-order images:. The calculation of auto-cumulants can be realized in a very attractive way in a mathematical sense. The n-th order cumulant can be calculated with a basic recursion from moments K n ( r → ) = μ n ( r → ) − ∑ i = 1 n − 1 ( n − 1 i ) K n − i ( r → ) μ i ( r → ) {\displaystyle K_{n}({\vec {r}})=\mu _{n}({\vec {r}})-\sum _{i=1}^{n-1}{\begin{pmatrix}n-1\\i\end{pmatrix}}K_{n-i}({\vec {r}})\mu _{i}({\vec {r}})} where K is a cumulant of the index's order, likewise μ {\displaystyle \mu } represents the moments. The term within the brackets indicates a binomial coefficient. This way of computation is straightforward in comparison with calculating cumulants with standard formulas. It allows for the calculation of cumulants with only little time of computing and is, as it is well implemented, even suitable for the calculation of high-order cumulants on large images. === Cross-cumulants === In a more advanced approach cross-cumulants are calculated by taking the information of several pixels into account. Cross-cumulants can be described as follows: C C n ( r → , τ 1 … n − 1 = 0 ) = ∏ j < l n U ( r → j − r → l n ) ⋅ ∑ i = 1 N U n ( r → i − ∑ k n r → k n ) ε i n w i ( 0 ) {\displaystyle CC_{n}({\vec {r}},\tau _{1\ldots n-1}=0)=\prod _{j

Coda (document editor)

Coda is a cloud-based multi-user document editor. == Features == Coda is a document editor that provides features from spreadsheets, presentation documents, word processor files, and apps. Possible uses for Coda documents include using them as a wiki, database, or project management tool. Coda has built a formula system, much like spreadsheets commonly have, but in Coda documents, formulas can be used anywhere within the document, and can link to things that aren't just cells, including other documents, calendars or graphs. Coda also has the ability to integrate with custom third-party services, and has automations. It has offered $1 million in grants for developers that create such integrations. == Development == Coda Project, Inc. was founded by Shishir Mehrotra and Alex DeNeui in June 2014. Having met at MIT, they developed the project mostly privately before announcing a public beta in October 2017. The company was named Coda, which is an anadrome for “a doc”. Coda raised $60 million in venture capital funding over two rounds by 2017. The Coda software came out of beta in February 2019. Version 1.0 had an improved user interface, new features for folders and workspaces, and permission levels for accessing files. Coda raised another $80 million in 2020, and $100 million in 2021. The 2021 funding brought Coda's valuation to $1.4 billion, making it a unicorn. In December 2024, Coda was acquired by Grammarly in an all-stock deal for an undisclosed amount. In October 2025, Grammarly rebranded as Superhuman, incorporating Coda as a core product within the new Superhuman productivity suite alongside Grammarly's writing tools, Superhuman Mail, and a new AI assistant called Superhuman Go.

Ann Copestake

Ann Alicia Copestake is professor of computational linguistics and head of the Department of Computer Science and Technology at the University of Cambridge and a fellow of Wolfson College, Cambridge. == Education == Copestake was educated at the University of Cambridge where she was awarded a Bachelor of Arts degree in Natural Sciences. After two years working for Unilever Research she completed the Cambridge Diploma in Computer Science. She went on to study at the University of Sussex where she was awarded a PhD in 1992 for research on lexical semantics supervised by Gerald Gazdar. == Career and research == Copestake started doing research in Natural language processing and Computational Linguistics at the University of Cambridge in 1985. Since then she has been a visiting researcher at Xerox PARC (1993/4) and the University of Stuttgart (1994/5). From July 1994 to October 2000 she worked at the Center for the Study of Language and Information (CSLI) at Stanford University, as a Senior Researcher. Copestake was appointed a University Lecturer at Cambridge in October 2000. In the UK, her research has been funded by the Engineering and Physical Sciences Research Council (EPSRC) and Arts and Humanities Research Council (AHRC). According to Google Scholar and Scopus her most cited publications include papers on minimal recursion semantics, multiword expressions, polysemy, named-entity recognition and feature structure grammars.

Peter Gerstoft

Peter Gerstoft is a Danish-American scientist and engineer specializing in ocean acoustics, seismology, and signal processing. He is currently a professor in the Department of Electrical and Photonics Engineering at the Technical University of Denmark. He was previously a Distinguished Data Scientist at the Scripps Institution of Oceanography at the University of California, San Diego and an adjunct professor in the Department of Electrical and Computer Engineering at UC San Diego. == Education == Gerstoft received his MSc in engineering from the Technical University of Denmark in 1983 and another MSc from the University of Western Ontario in 1984. He completed his PhD in engineering at the Technical University of Denmark in 1986. == Career == Gerstoft began his career in acoustics and vibrations at Odegaard & Danneskiold-Samsøe (1987–1992). He then served as a Senior Scientist at the NATO SACLANT Undersea Research Centre in La Spezia, Italy, from 1992 to 1997. Between 1999 and 2000, Gerstoft worked as a Senior Seismic Acoustic Officer with the Comprehensive Nuclear-Test-Ban Treaty Organization. He has been a Data Scientist at the Scripps Institution of Oceanography since 1997. From 2013, he held an adjunct faculty position in Electrical and Computer Engineering at UC San Diego, where he taught courses on seismology, data assimilation, and machine learning for physical systems. Gerstoft retired from UC San Diego in 2025 and accepted an appointment as Professor of Electrical and Photonics Engineering at the Technical University of Denmark in 2026 . == Research and contributions == Gerstoft's research focuses on environmental signal processing, with a particular emphasis on inversion methods, including their theoretical development, algorithmic implementation, and practical applications. In the 1990s, he investigated the use of nonlinear optimization and Bayesian approaches in acoustic inverse problems related to source localization and environmental parameter estimation. His work integrated physical propagation models with Bayesian sampling methods and a range of likelihood functions. These techniques have been applied to various data types, including vertical sensor arrays, single-sensor broadband data, and transmission loss measurements, and contributed to a general framework for inversion based on Gaussian assumptions. He has also conducted research in machine learning and sparse signal processing, particularly in the context of sensor array data. This includes applications such as direction of arrival estimation and source localization, including for seismic events such as the 2011 Tōhoku earthquake and for ship tracking in ocean environments. His work on sparse Bayesian sequential methods and techniques for estimating Lagrange multipliers in constrained optimization problems has contributed to the development of adaptive and high-resolution signal processing techniques. Gerstoft has applied supervised learning and deep neural networks to problems in physical acoustics, including source localization in ocean waveguides. He has also co-authored several review articles on the use of machine learning in acoustics and seismology. == Honors == Fulbright Scholar, Massachusetts Institute of Technology (1989–1990) Fellow, Acoustical Society of America (2003) Member, American Geophysical Union (since 2004) Senior Member, Institute of Electrical and Electronics Engineers (2018) Fellow, Institute of Electrical and Electronics Engineers (2023) == Selected publications == === Book === Diachok, O., Caiti, A., Gerstoft, P., & Schmidt, H. (Eds.). Full Field Inversion Methods in Ocean and Seismo-Acoustics. Kluwer Academic Publishers, 1995. === Selected articles === Gerstoft, P. (1994). "Inversion of seismo-acoustic data using genetic algorithms and a posteriori probability distributions". Journal of the Acoustical Society of America. 95 (2): 770–782. doi:10.1121/1.408467. Gerstoft, P., & Mecklenbrauker, C. F. (1998). "Ocean acoustic inversion with estimation of a posteriori probability distributions". Journal of the Acoustical Society of America. 104 (2): 808–819. doi:10.1121/1.423287. Sabra, K. G., Gerstoft, P., Roux, P., Kuperman, W. A., & Fehler, M. (2005). "Extracting time-domain Green's function estimates from ambient seismic noise". Geophysical Research Letters. 32, L03310. Xenaki, A., Gerstoft, P., & Mosegaard, K. (2014). "Compressive beamforming". Journal of the Acoustical Society of America. 136, 260–271. Niu, H., Reeves, D., & Gerstoft, P. (2017). "Source localization in an ocean waveguide using supervised machine learning". Journal of the Acoustical Society of America. 142, 1176–1188.

Wang-Chiew Tan

Wang-Chiew Tan is a Singaporean computer scientist specializing in data management and natural language processing. Her work in data management includes data provenance (or data lineage) and data integration. She is currently a Research Scientist at Facebook AI, and was previously the Director of Research at Megagon Labs in Mountain View, California. At Megagon Labs, Tan was the lead researcher on a study with the University of Tokyo that concluded that the company of other people is more effective than pets at making people happy. == Education and career == Tan earned her bachelor's degree in computer science (first-class) at the National University of Singapore, and completed her Ph.D. at the University of Pennsylvania. Her 2002 dissertation, Data Annotations, Provenance, and Archiving, was jointly supervised by Peter Buneman and Sanjeev Khanna. Before working at Megagon, she has been a professor of computer science at the University of California, Santa Cruz beginning in 2002, and, from 2010 to 2012, was on leave from Santa Cruz as a researcher at IBM Research - Almaden. == Recognition == Tan was named a Fellow of the Association for Computing Machinery in 2015 "for contributions to data provenance and to the foundations of information integration".

Afghan Girls Robotics Team

The Afghan Girls Robotics Team, also known as the Afghan Dreamers, is an all-girl robotics team from Herat, Afghanistan, founded through the Digital Citizen Fund (DCF) in 2017 by Roya Mahboob and Alireza Mehraban. It is made up of girls between ages 12 and 18 and their mentors. Several members of the team were relocated to Qatar and Mexico by humanitarian and tech entrepreneur Sarah Porter following the fall of Kabul in August 2021. A documentary film featuring members of the team, titled Afghan Dreamers, was released by MTV Documentary Films in 2023. == Origins == The Afghan Girls Robotics Team was co-founded in 2017 by Roya Mahboob, who is their coach, mentor and sponsor, and founder of the Digital Citizen Fund (DCF), which is the parent organization for the team. Dean Kamen was planning a 2017 competition in the United States and had recruited Mahboob to form a team from Afghanistan. Out of 150 girls, 12 were selected for the first team. Before parts were sent by Kamen, they trained in the basement of the home of Mahboob's parents, with scrap metal and without safety equipment under the guidance of their coach, Mahboob's brother Alireza Mehraban, who is also a co-founder of the team. == 2017 and 2018 == In 2017, six members of the Afghan Girls Robotics Team traveled to the United States to participate in the international FIRST Global Challenge robotics competition. Their visas were rejected twice after they made two journeys from Herat to Kabul through Taliban-controlled areas, before officials in the United States government intervened to allow them to enter the United States. Customs officials also detained their robotics kits, which left them two weeks to construct their robot, unlike some teams that had more time. They were awarded a Silver medal for Courageous Achievement. One week after they returned home from the competition, the father of team captain Fatemah Qaderyan, Mohammad Asif Qaderyan, was killed in a suicide bombing. After their United States visas expired, the team participated in competitions in Estonia and Istanbul. Three of the 12 members participated in the 2017 Entrepreneurial Challenge at the Robotex festival in Estonia, and won the competition for their solar-powered robot designed to assist farmers. In 2018, the team trained in Canada, continued to travel in the United States for months and participate in competitions. == 2019 == The Afghan Girls Robotics team had aspirations to develop a science and technology school for girls in Afghanistan. Roya Mahboob interfaced with the School of Engineering and Applied Sciences (SEAS), the School of Architecture, and the Whitney and Betty MacMillan Center for International and Area Studies Yale University to design the infrastructure for what they named The Dreamer Institute. == 2020 == In March 2020, the governor of Herat at the time, in response to the COVID-19 pandemic in Afghanistan and a scarcity of ventilators, sought help with the design of low-cost ventilators, and the Afghan Girls Robotics Team was one of six teams contacted by the government. Using a design from Massachusetts Institute of Technology and with guidance from MIT engineers and Douglas Chin, a surgeon in California, the team developed a prototype with Toyota Corolla parts and a chain drive from a Honda motorcycle. UNICEF also supported the team with the acquisition of necessary parts during the three months they spent building the prototype that was completed in July 2020. Their design costs around $500 compared to $50,000 for a ventilator. In December 2020, Minister of Industry and Commerce Nizar Ahmad Ghoryani donated funding and obtained land for a factory to produce the ventilators. Under the direction of their mentor Roya Mahboob, the Afghan Dreamers also designed a UVC Robot for sanitization, and a Spray Robot for disinfection, both of which were approved by the Ministry of Health for production. == 2021 == In early August 2021, Somaya Faruqi, former captain of the team, was quoted by Public Radio International about the future of Afghanistan, stating, "We don’t support any group over another but for us what’s important is that we be able to continue our work. Women in Afghanistan have made a lot of progress over the past two decades and this progress must be respected." On August 17, 2021, the Afghan Girls Robotics Team and their coaches were reported to be attempting to evacuate, but unable to obtain a flight out of Afghanistan, and a lawyer appealed to Canada for assistance regarding the evacuation of the team members. As of August 19, 2021, nine members of the team and their coaches had evacuated to Qatar. The founder of the team, Roya Mahboob, and DCF board member, Elizabeth Schaeffer Brown, were previously in contact with the Qatari government to assist the team members in their evacuation from Afghanistan. By August 25, 2021, some members arrived in Mexico. Saghar, a team member who evacuated to Mexico, said, "We wanted to continue the path that we started to continue to go for our achievements and to go for having our dreams through reality. So that's why we decided to leave Afghanistan and go for somewhere safe" in an interview with The Associated Press. The members who have left Afghanistan participated in an online robotics competition in September and plan to continue their education. A documentary film titled Afghan Dreamers, produced by Beth Murphy and directed by David Greenwald, was in post-production when the team began to evacuate. == 2022 == The Afghan Dreamers were involved in a training program at the Texas A&M University at Qatar’s STEM Hub. == 2023 == The Afghan Girls Robotics Team had a booth at the 5th UN Conference on the Least Developed Countries, where they displayed some of the robots the team had constructed. == Afghan Dreamers documentary == The Afghan Dreamers documentary from MTV Documentary Films premiered in May 2023 on Paramount+. The film was directed by David Greenwald and produced by David Cowan and Beth Murphy. In a review for Screen Daily, Wendy Ide wrote, "This film, with its likeable cast of girl nerds and positive message, should enjoy a warm reception on the festival circuit, and will be of particular interest to events seeking to showcase women's stories from around the world. It also serves as a timely cautionary tale – a case study on just how quickly the rights and the opportunities of women can be curtailed, at the behest of the men in power." == Honors and awards == 2017 Silver medal for Courageous Achievement at the FIRST Global Challenge, science and technology 2017 Benefiting Humanity in AI Award at World Summit AI 2017 Winner, Entrepreneurship Challenge at Robotex in Estonia 2018 Permission to Dream Award, Raw Film Festival 2018 Conrad Innovation Challenge, Raw Film Festival 2018 Rookie All Star – District Championship, Canada 2018 Asia Game Changer Award Honoree 2019 Inspiring in Engineering Award – FIRST Detroit World Championship 2019 Asia Game Changer Award of California 2019 Safety Award – FIRST Global, Dubai 2021 Forbes 30 Under 30 Asia 2022 World Championships, Genoa, Switzerland

Andrei Knyazev (mathematician)

Andrew Knyazev is an American mathematician. He graduated from the Faculty of Computational Mathematics and Cybernetics of Moscow State University under the supervision of Evgenii Georgievich D'yakonov (Russian: Евгений Георгиевич Дьяконов) in 1981 and obtained his PhD in Numerical Mathematics at the Russian Academy of Sciences under the supervision of Vyacheslav Ivanovich Lebedev (Russian: Вячеслав Иванович Лебедев) in 1985. He worked at the Kurchatov Institute between 1981–1983, and then to 1992 at the Marchuk Institute of Numerical Mathematics (Russian: ru:Институт вычислительной математики имени Г. И. Марчука РАН) of the Russian Academy of Sciences, headed by Gury Marchuk (Russian: Гурий Иванович Марчук). From 1993–1994, Knyazev held a visiting position at the Courant Institute of Mathematical Sciences of New York University, collaborating with Olof B. Widlund. From 1994 until retirement in 2014, he was a Professor of Mathematics at the University of Colorado Denver, supported by the National Science Foundation and United States Department of Energy grants. He was a recipient of the 2008 Excellence in Research Award, the 2000 college Teaching Excellence Award, and a finalist of the CU President's Faculty Excellence Award for Advancing Teaching and Learning through Technology in 1999. He was awarded the title of Professor Emeritus at the University of Colorado Denver and named the SIAM Fellow Class of 2016 and AMS Fellow Class of 2019. From 2012–2018, Knyazev worked at the Mitsubishi Electric Research Laboratories on algorithms for image and video processing, data sciences, optimal control, and material sciences, resulting in dozens of publications and 13 patent applications. Since 2018, he contributed to numerical techniques in quantum computing at Zapata Computing, real-time embedded anomaly detection in automotive data, and algorithms for silicon photonics-based hardware. Knyazev is mostly known for his work in numerical solution of large sparse eigenvalue problems, particularly preconditioning and the iterative method LOBPCG. Knyazev's implementation of LOBPCG is available in many open source software packages, e.g., BLOPEX, SciPy, and ABINIT. Knyazev collaborated with John Osborn on the theory of the Ritz method in the finite element method context and with Nikolai Sergeevich Bakhvalov (Russian: Николай Серге́евич Бахвалов) (Erdős number 3 via Leonid Kantorovich) on numerical solution of elliptic partial differential equations with large jumps in the main coefficients. Jointly with his Ph.D. students, Knyazev pioneered using majorization for bounds in the Rayleigh–Ritz method (see and references there) and contributed to the theory of angles between flats.