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Design, synthesis, inhibitory activity, and molecular simulations study for D-glucose-conjugated thioureas containing pyrimidine ring as multitarget inhibitors against α-amylase, α-glucosidase, DDP-4, and PTP1B in Type 2 diabetes mellitus

RSC Med. Chem., 2024, 15,3395-3417
DOI: 10.1039/D4MD00334A, Research Article
Vu Ngoc Toan, Do Son Hai, Hoang Thi Kim Van, Nguyen Minh Tri, Duong Ngoc Toan, Nguyen Thi Thanh Mai, Nguyen Dinh Thanh
D-Glucose-conjugated thioureas from 2-aminopyrimidines had inhibitory activity against α-amylase, α-glucosidase, DPP-4, PTP1B. The cytotoxicity, inhibitory kinetics, and molecular simulations of the most potent inhibitors 8k, 8j, 8f, and 8h were studied.
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Lead optimisation of OXS007417: in vivo PK profile and hERG liability modulation to optimise a small molecule differentiation agent for the potential treatment of acute myeloid leukaemia

RSC Med. Chem., 2024, 15,3495-3506
DOI: 10.1039/D4MD00275J, Research Article
Open Access
  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Thomas J. Cogswell, Laia Josa-Culleré, David Zimmer, Sébastien R. G. Galan, Morgan Jay-Smith, Kate S. Harris, Carole J. R. Bataille, Thomas R. Jackson, Douzi Zhang, Stephen G. Davies, Paresh Vyas, Thomas A. Milne, Graham M. Wynne, Angela J. Russell
The optimisation of a class of AML differentiation agents is described to show improved potency, solubility and stability, reduced off target toxicity, and tumour regression in a murine model in vivo.
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Development, biological evaluation, and molecular modelling of some benzene-sulfonamide derivatives as protein tyrosine phosphatase-1B inhibitors for managing diabetes mellitus and associated metabolic disorders

RSC Med. Chem., 2024, Advance Article
DOI: 10.1039/D4MD00594E, Research Article
Nagat Ghareb, Khaled M. Darwish, Mohamed S. Nafie, Ranwa Elrayess, Noha M. Abourobe, Shaimaa A. Fattah, Reem M. Hazem, Eman T. Mehanna, Ranza Elrayess
One benzene-sulfonamide derivative exhibited potent protein tyrosine phosphatase-1B inhibition for managing diabetes mellitus and associated metabolic disorders.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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Miniaturized click chemistry and direct screening facilitate the discovery of triazole piperazine SARS-CoV-2 Mpro inhibitors with improved metabolic stability

RSC Med. Chem., 2024, Advance Article
DOI: 10.1039/D4MD00555D, Research Article
Shenghua Gao, Letian Song, Bing Ye, Mianling Yang, Junyi Li, Manyu Gu, Ann E. Tollefson, Karoly Toth, Peng Zhan, Xinyong Liu
The continuous mutational nature of SARS-CoV-2 and its inter-species' similarities emphasize the urgent need to design and develop more direct-acting antiviral agents against highly infectious variants.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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Changes in train services notified due to demolition of old bridge near Tiruchi junction




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Urban Primary Health Centre stuck in cramped, temporary facility




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High-level committee formed to facilitate clearances for companies that signed MoU, says Minister

Constant monitoring was being done now from the time of signing of MoUs to providing employment in new industrial units, says Industries Minister T.R.B. Rajaa




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Fishermen seek healthcare and cold storage facilities




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Art and literary contests lined up for District Central Library’s National Library Week




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585: Blog Redesign, Sounds on a Website, Accessibility Tests, and Safari 17

Chris redesigned his blog, using sounds on your website to make it seem fancy, what can't automated accessibility tests test, and what's new in Safari 17.




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588: Elliott Marquez on Web Components and Lit

Elliot Marquez talks with us about the history of Polymer and Lit, why you should pick Lit, working with web components, the shadow dom, managing state, and how Material design is built with web components.




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602: What Does Accessibility Really Mean?

Voiceover pays us a visit, we talk about what accessibility really means, the difficulty of closing a dialogue element, web components at work, and jQuery 4 is out.




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606: Web Sustainability with Michelle Barker

Show DescriptionWe're talking with Michelle Barker about the idea of paying to support bloggers (and podcasters!) via services like Patreon, drumming as a fun side gig from CSS, how big of an issue digital sustainability is, trying to understand the environmental impact of our websites and digital life, wondering why YouTube embeds are still so […]




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621: Setting Up Prettier and Linting, Comparing Colors, and Accessibility Overlays

We've got follow up on Cloudflare and Cara from last episode, a question about setting up Prettier and auto linting, a cool tool from a listener on comparing colors, a question about using tooling like Craft or more user friendly apps like Webflow when working with clients, and our takes on accessibility overlays.




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Improve quality of indoor air

Outdoor air pollutants are impacting the indoor environment and builders have to take remedial measures, says M.A. Siraj




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Green dream a reality now

Chennai-based green building consultant Sumitra Vasudevan gives tips on how to ensure your home has a low carbon footprint.




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Alternatives and affordability

Each housing project has to be site-specific, culturally appropriate and climatically conforming.




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Rooting for sustainability

At the World Bamboo Congress held in Korea this year, Rebecca Reubens spoke about bamboo’s potential for holistic sustainability through design.




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Navigating the flood of healthcare information, with a little help from AI

A global survey maps how willing, and equipped clinicians are in using artificial intelligence to support their work 




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Jamiat cautions NDA partners, says ‘crutches’ cannot escape responsibility for Waqf Bill

The Jamiat Ulama-i-Hind urged NDA partners TDP and JD(U) to heed Muslim sentiments on the contentious issue surrounding the Waqf (Amendment) Bill, 2024




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HC tells jail authority to decide plea on lack of facilities for visiting lawyers




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Air quality 'very poor' in Delhi

Delhi’s air quality remains “very poor” with some areas in the “severe” category, despite a slight improvement




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Delhi's air quality remains 'very poor', AQI at 367

The minimum temperature in Delhi was recorded at 18.0 degrees Celsius, 3.7 notches warmer than usual.




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Delhi's air quality remains 'very poor' on November 8

Meanwhile, a thick layer of morning mist and smog blanketed the city as the minimum temperature dropped to 18.1 degrees Celsius, 3.8 degrees above normal; AQI stood at 387




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Delhi’s air quality remains ‘very poor’, layer of smog over city for ninth day post-Diwali

Delhi’s air quality reaches severe levels, blamed on stubble-burning, Diwali fireworks, and low wind speed




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Accessibility for disabled persons is a human and a fundamental right: SC judgment

The court asked the government to enable the creation of public and private spaces, services and products of an ‘universal design’ which could be accessed by everyone, regardless of their ability, age, or status




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Three juveniles held for murder in Delhi; political row erupts over city’s crime rate




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Delhi air quality ‘very poor’ on November 10

The National Capital wakes up to toxic air with AQI at 334, ‘very poor’ air quality due to stubble-burning, Diwali fireworks, and low wind speed




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Delhi’s air quality ‘very poor’ to ‘severe’ on November 11

Delhi’s air quality persists in the ‘very poor’ category more than a week post-Deepavali




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Can India arrest income inequality?

Thomas Piketty’s prescriptions are too radical. Dattopant Thengadi’s vision is more useful for us




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A deep look into China’s realities

Ananth Krishnan shines a light on the different sides of China that largely remain hidden from Indian citizens




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The inevitability of uncertainty

The book tells us quite convincingly that the future is unknown. But it does not offer an alternative




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Straddling royalty and politics

A riveting account of Scindias’ royal and political journey




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Indian influence in US polity, culture

From Kamal Harris to Mindy Kaling — this book charts the Indian story in America




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Policy prescription for economic and political maladies

Bimal Jalan delves deep into issues that are critical to the country with suggestions on how to overcome challenges 




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International conference to recommend policies to address gender inequality at farms

“The conference aims to promote the sharing of cutting-edge knowledge on gender and inclusion in agri-food systems.”




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GI tag sought for the Senkanthal seed whose flower holds a special place in Tamil literature

Minister for Agriculture and Farmer’s Welfare M.R.K.Panneerselvam, while presenting the State’s Agriculture Budget, had said that Geographical Indication tag would be obtained for 10 agricultural products at a cost of ₹30 lakh




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In Assam, banks suffer from ‘militancy hangover’: experts

The absence of bank linkage is affecting optimum production by 25 lakh small and marginal farmers in the State, they said




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Observability and mathematics [electronic resource] : Quantum Yang-Mills theory and modelling / Boris Khots.




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Quality of farm loans by Indian banks won’t weaken: Moody’s




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FPIs take out ₹58,711 crore from equities in October on geopolitical crisis, strong Chinese stocks

The outflow came following a nine-month high investment of ₹57,724 crore in September




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Free salon for persons with disabilities inaugurated in Vellore




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Litigant withdraws PIL seeking revival of 2001 flyover construction scam case against T.N. CM Stalin

The Madras High Court also permits him to withdraw ₹1 lakh deposited in April this year to prove his bona fide intention




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Organic/inorganic heterostructures templated by interfacial instability-driven BCP colloids in deformable emulsion droplets

Soft Matter, 2024, 20,8174-8180
DOI: 10.1039/D4SM00921E, Communication
Yuqing Song, Nan Yan, Lingli Wan, Jingjing Li, Ye Gao
Core–shell colloids are self-assembled in emulsion droplets driven by interfacial instability, which serve as excellent scaffolds for designing organic/inorganic heterostructures.
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Bubbles and drops between circular frames: shape, force and stability analysis

Soft Matter, 2024, 20,8420-8435
DOI: 10.1039/D4SM00919C, Paper
Open Access
Friedrich Walzel, Jonathan Dijoux, Leandro Jacomine, Élodie Harle, Pierre Muller, Thierry Charitat, Wiebke Drenckhan
Combining experiments, simulations and theory, we provide a complete shape analysis of two bubbles held by circular frames in the parameter space of different frame radii, distances between frames and contact angle between bubbles (0°, 60° and 90°).
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Optimality and cooperativity in superselective surface binding by multivalent DNA nanostars

Soft Matter, 2024, 20,8515-8523
DOI: 10.1039/D4SM00704B, Paper
Open Access
  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Christine Linne, Eva Heemskerk, Jos W. Zwanikken, Daniela J. Kraft, Liedewij Laan
Our study shows that DNA nanostars with three binding sites (ligands) can (1) bind superselectively to surfaces based on receptor density, and (2) that interactions between ligands affect the optimum number of ligands required for superselectivity.
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Aging iridium oxide catalyst inks: a formulation strategy to enhance ink processability for polymer electrolyte membrane water electrolyzers

Soft Matter, 2024, Advance Article
DOI: 10.1039/D4SM00987H, Paper
Open Access
  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Sunilkumar Khandavalli, Jae Hyung Park, Robin Rice, Diana Y. Zhang, Sarah A. Berlinger, Guido Bender, Deborah J. Myers, Michael Ulsh, Scott A. Mauger
Steady-shear rheology showing evolution of the microstructure of iridium oxide catalyst inks of PEM water electrolyzers with aging time.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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The influence of active agent motility on SIRS epidemiological dynamics

Soft Matter, 2024, Advance Article
DOI: 10.1039/D4SM00864B, Paper
Open Access
R. Kailasham, Aditya S. Khair
Motility induced phase separation of active disks with SIRS epidemiological dynamics.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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Future Accessibility Guidelines—for People Who Can’t Wait to Read Them

Alan Dalton uses this, the International Day of Persons with Disabilities, to look back at where we’ve come from, to evaluate where we are, and to look forward to what’s coming next in the future of accessibility guidelines.


Happy United Nations International Day of Persons with Disabilities! The United Nations have chosen “Promoting the participation of persons with disabilities and their leadership: taking action on the 2030 Development Agenda” for this year’s observance. Let’s see how the World Wide Web Consortium (W3C)’s Web Accessibility Initiative (WAI) guidelines of accessibility past, present, and yet-to-come can help us to follow that goal, and make sure that the websites—and everything else!—that we create can include as many potential users as possible.

Guidelines of Accessibility Past

The W3C published the Web Content Accessibility Guidelines (WCAG) 1.0 on 5th May 1999, when most of us were playing Snake on our Nokia 3210s’ 1.5” monochrome screens…a very long time ago in technology terms. From the start, those guidelines proved enlightening for designers and developers who wanted to avoid excluding users from their websites. For example, we learned how to provide alternatives to audio and images, how to structure information, and how to help users to find the information they needed. However, those guidelines were specific to the web technologies of the time, resulting in limitations such as requiring developers to “use W3C technologies when they are available […]”. Also, those guidelines became outdated; I doubt that you, gentle reader, consult their technical documentation about “directly accessible applets” or “Writing for browsers that do not support FRAME” in your day-to-day work.

Guidelines of Accessibility Present

The W3C published the Web Content Accessibility Guidelines (WCAG) 2.0 on 11th December 2008, when most of us were admiring the iPhone 3G’s innovative “iPhone OS 2.0” software…a long time ago in technology terms. Unlike WCAG 1, these guidelines also applied to non-W3C technologies, such as PDF and Flash. These guidelines used legalese and future-proofed language, with terms such as “time-based media” and “programmatically determined”, and testable success criteria. This made these guidelines more difficult for designers and developers to grasp, but also enabled the guidelines to make their way into international standards (see EN 301 549 — Accessibility requirements suitable for public procurement of ICT products and services in Europe and ISO/IEC 40500:2012 Information technology — W3C Web Content Accessibility Guidelines (WCAG) 2.0) and even international law (see EU Directive 2016/2102 … on the accessibility of the websites and mobile applications of public sector bodies).

More importantly, these guidelines enabled designers and developers to create inclusive websites, at scale. For example, in the past 18 months:

The updated Web Content Accessibility Guidelines (WCAG) 2.1 arrived on 5th June last year—almost a 10-year wait for a “.1” update!—and added 17 new success criteria to help bring the guidelines up to date. Those new criteria focused on people using mobile devices and touchscreens, people with low vision, and people with cognitive and learning disabilities.

(If you need to get up to speed with these guidelines, take 36 minutes to read “Web Content Accessibility Guidelines—for People Who Haven’t Read Them” and Web Content Accessibility Guidelines 2.1—for People Who Haven’t Read the Update.)

Guidelines of Accessibility Yet to Come

So, what’s next? Well, the W3C hope to release another minor update (WCAG 2.2) in November 2020. However, they also have a Task Force working on produce major new guidelines with wider scope (more people, more technologies) and fewer limitations (easier to understand, easier to use) in November 2022. These next guidelines will have a different name, because they will cover more than “Web” and “Content”. Andrew Kirkpatrick (Adobe’s Head of Accessibility) named the Task Force “Silver” (because the initials of “Accessibility Guidelines” form the symbol of the silver element).

The Silver Task Force want the next major accessibility guidelines to:

  • take account of more disabilities;
  • apply to more technologies than just the web, including virtual reality, augmented reality, voice assistants, and more;
  • consider all the technologies that people use, including authoring tools, browsers, media players, assistive technologies (including screen readers and screen magnifiers), application software, and operating systems.

That’s quite a challenge, and so the more people who can help, the better. The Silver Task Force wanted an alternative to W3C’s Working Groups, which are made up of employees of organisations who are members of the W3C, and invited experts. So, they created a Silver Community Group to allow everyone to contribute towards this crucial work. If you want to join right now, for free, just create a W3C account.

Like all good designers, the Silver Task Force and Silver Community Group began by researching. They examined the problems that people have had when using, conforming to, and maintaining the existing accessibility guidelines, and then summarised that research. From there, the Silver Community Group drafted ambitious design principles and requirements. You can read about what the Silver Community Group are currently working on, and decide whether you would like to get involved now, or at a later stage.

Emphasise expertise over empathy

Remember that today’s theme is “Promoting the participation of persons with disabilities and their leadership: taking action on the 2030 Development Agenda”. (The United Nations’ 2030 Development Agenda is outside the scope of this article, but if you’re looking to be inspired, read Alessia Aquaro’s article on Public Digital’s blog about how digital government can contribute to the UN’s Sustainable Development Goals.) In line with this theme, if you don’t have a disability and you want to contribute to the Silver Community Group, resist the temptation to try to empathise with people with disabilities. Instead, take 21 minutes during this festive season to enjoy the brilliant Liz Jackson explaining how empathy reifies disability stigmas, and follow her advice.

Choose the right route

I think we can expect the next Accessibility Guidelines to make their way into international standards and international law, just like their predecessors. We can also expect successful companies to apply them at scale. If you contribute to developing those guidelines, you can help to make sure that as many people as possible will be able to access digital information and services, in an era when that access will be crucial to every aspect of people’s lives. As Cennydd Bowles explained in “Building Better Worlds”, “There is no such thing as the future. There are instead a near-infinity of potential futures. The road as-yet-untravelled stretches before us in abundant directions. We get to choose the route. There is no fate but what we make.”


About the author

Alan Dalton worked for Ireland’s National Disability Authority for 9½ years, mostly as Accessibility Development Advisor. That involved working closely with public sector bodies to make websites, services, and information more accessible to all users, including users with disabilities. Before that, he was a consultant and trainer for Software Paths Ltd. in Dublin. In his spare time, he maintains StrongPasswordGenerator.com to help people stay safe online, tweets, and takes photos.

More articles by Alan




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Usability and Security; Better Together

Divya Sasidharan calls into question the trade-offs often made between security and usability. Does a secure interface by necessity need to be hard to use? Or is it the choice we make based on years of habit? Snow has fallen, snow on snow.


Security is often synonymous with poor usability. We assume that in order for something to be secure, it needs to by default appear impenetrable to disincentivize potential bad actors. While this premise is true in many instances like in the security of a bank, it relies on a fundamental assumption: that there is no room for choice.

With the option to choose, a user almost inevitably picks a more usable system or adapts how they interact with it regardless of how insecure it may be. In the context of the web, passwords are a prime example of such behavior. Though passwords were implemented as a way to drastically reduce the risk of attack, they proved to be marginally effective. In the name of convenience, complex, more secure passwords were shirked in favor of easy to remember ones, and passwords were liberally reused across accounts. This example clearly illustrates that usability and security are not mutually exclusive. Rather, security depends on usability, and it is imperative to get user buy-in in order to properly secure our applications.

Security and Usability; a tale of broken trust

At its core, security is about fostering trust. In addition to protecting user accounts from malicious attacks, security protocols provide users with the peace of mind that their accounts and personal information is safe. Ironically, that peace of mind is incumbent on users using the security protocols in the first place, which further relies on them accepting that security is needed. With the increased frequency of cyber security threats and data breaches over the last couple of years, users have grown to be less trusting of security experts and their measures. Security experts have equally become less trusting of users, and see them as the “the weakest link in the chain”. This has led to more cumbersome security practices such as mandatory 2FA and constant re-login flows which bottlenecks users from accomplishing essential tasks. Because of this break down in trust, there is a natural inclination to shortcut security altogether.

Build a culture of trust not fear

Building trust among users requires empowering them to believe that their individual actions have a larger impact on the security of the overall organization. If a user understands that their behavior can put critical resources of an organization at risk, they will more likely behave with security in mind. For this to work, nuance is key. Deeming that every resource needs a similarly high number of checks and balances diminishes how users perceive security and adds unnecessary bottlenecks to user workflows.

In order to lay the foundation for good security, it’s worth noting that risk analysis is the bedrock of security design. Instead of blindly implementing standard security measures recommended by the experts, a better approach is to tailor security protocols to meet specific use cases and adapt as much as possible to user workflows. Here are some examples of how to do just that:

Risk based authentication

Risk based authentication is a powerful way to perform a holistic assessment of the threats facing an organization. Risks occur at the intersection of vulnerability and threat. A high risk account is vulnerable and faces the very real threat of a potential breach. Generally, risk based authentication is about calculating a risk score associated with accounts and determining the proper approach to securing it. It takes into account a combination of the likelihood that that risk will materialize and the impact on the organization should the risk come to pass. With this system, an organization can easily adapt access to resources depending on how critical they are to the business; for instance, internal documentation may not warrant 2FA, while accessing business and financial records may.

Dynamically adaptive auth

Similar to risk based auth, dynamically adaptive auth adjusts to the current situation. Security can be strengthened and slackened as warranted, depending on how risky the access point is. A user accessing an account from a trusted device in a known location may be deemed low risk and therefore not in need of extra security layers. Likewise, a user exhibiting predictive patterns of use should be granted quick and easy access to resources. The ability to adapt authentication based on the most recent security profile of a user significantly improves the experience by reducing unnecessary friction.

Conclusion

Historically, security failed to take the user experience into account, putting the onus of securing accounts solely on users. Considering the fate of password security, we can neither rely on users nor stringent security mechanisms to keep our accounts safe. Instead, we should aim for security measures that give users the freedom to bypass them as needed while still protecting our accounts from attack. The fate of secure systems lies in the understanding that security is a process that must constantly adapt to face the shifting landscape of user behavior and potential threats.


About the author

Divya is a web developer who is passionate about open source and the web. She is currently a developer experience engineer at Netlify, and believes that there is a better workflow for building and deploying sites that doesn’t require a server—ask her about the JAMstack. You will most likely find her in the sunniest spot in the room with a cup of tea in hand.

More articles by Divya