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Open Access Theses and Dissertations

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About OATD.org

OATD.org aims to be the best possible resource for finding open access graduate theses and dissertations published around the world. Metadata (information about the theses) comes from over 1100 colleges, universities, and research institutions . OATD currently indexes 7,241,108 theses and dissertations.

About OATD (our FAQ) .

Visual OATD.org

We’re happy to present several data visualizations to give an overall sense of the OATD.org collection by county of publication, language, and field of study.

You may also want to consult these sites to search for other theses:

• Google Scholar
• NDLTD , the Networked Digital Library of Theses and Dissertations. NDLTD provides information and a search engine for electronic theses and dissertations (ETDs), whether they are open access or not.
• Proquest Theses and Dissertations (PQDT), a database of dissertations and theses, whether they were published electronically or in print, and mostly available for purchase. Access to PQDT may be limited; consult your local library for access information.

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EBSCO Open Dissertations

EBSCO Open Dissertations makes electronic theses and dissertations (ETDs) more accessible to researchers worldwide. The free portal is designed to benefit universities and their students and make ETDs more discoverable. 

Increasing Discovery & Usage of ETD Research

EBSCO Open Dissertations is a collaboration between EBSCO and BiblioLabs to increase traffic and discoverability of ETD research. You can join the movement and add your theses and dissertations to the database, making them freely available to researchers everywhere while increasing traffic to your institutional repository. 

EBSCO Open Dissertations extends the work started in 2014, when EBSCO and the H.W. Wilson Foundation created American Doctoral Dissertations which contained indexing from the H.W. Wilson print publication, Doctoral Dissertations Accepted by American Universities, 1933-1955. In 2015, the H.W. Wilson Foundation agreed to support the expansion of the scope of the American Doctoral Dissertations database to include records for dissertations and theses from 1955 to the present.

How Does EBSCO Open Dissertations Work?

Your ETD metadata is harvested via OAI and integrated into EBSCO’s platform, where pointers send traffic to your IR.

EBSCO integrates this data into their current subscriber environments and makes the data available on the open web via opendissertations.org .

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Open Access Theses and Dissertations (OATD)

OATD.org provides open access graduate theses and dissertations published around the world. Metadata (information about the theses) comes from over 1100 colleges, universities, and research institutions. OATD currently indexes 6,654,285 theses and dissertations.

MIT Libraries home DSpace@MIT

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This collection of MIT Theses in DSpace contains selected theses and dissertations from all MIT departments. Please note that this is NOT a complete collection of MIT theses. To search all MIT theses, use MIT Libraries' catalog .

MIT's DSpace contains more than 58,000 theses completed at MIT dating as far back as the mid 1800's. Theses in this collection have been scanned by the MIT Libraries or submitted in electronic format by thesis authors. Since 2004 all new Masters and Ph.D. theses are scanned and added to this collection after degrees are awarded.

MIT Theses are openly available to all readers. Please share how this access affects or benefits you. Your story matters.

If you have questions about MIT theses in DSpace, [email protected] . See also Access & Availability Questions or About MIT Theses in DSpace .

If you are a recent MIT graduate, your thesis will be added to DSpace within 3-6 months after your graduation date. Please email [email protected] with any questions.

Permissions

MIT Theses may be protected by copyright. Please refer to the MIT Libraries Permissions Policy for permission information. Note that the copyright holder for most MIT theses is identified on the title page of the thesis.

Theses by Department

• Comparative Media Studies
• Computation for Design and Optimization
• Computational and Systems Biology
• Department of Aeronautics and Astronautics
• Department of Architecture
• Department of Biological Engineering
• Department of Biology
• Department of Brain and Cognitive Sciences
• Department of Chemical Engineering
• Department of Chemistry
• Department of Civil and Environmental Engineering
• Department of Earth, Atmospheric, and Planetary Sciences
• Department of Economics
• Department of Electrical Engineering and Computer Sciences
• Department of Humanities
• Department of Linguistics and Philosophy
• Department of Materials Science and Engineering
• Department of Mathematics
• Department of Mechanical Engineering
• Department of Nuclear Science and Engineering
• Department of Ocean Engineering
• Department of Physics
• Department of Political Science
• Department of Urban Studies and Planning
• Engineering Systems Division
• Harvard-MIT Program of Health Sciences and Technology
• Institute for Data, Systems, and Society
• Media Arts & Sciences
• Operations Research Center
• Program in Real Estate Development
• Program in Writing and Humanistic Studies
• Science, Technology & Society
• Science Writing
• Sloan School of Management
• Supply Chain Management
• System Design & Management
• Technology and Policy Program

Collections in this community

Doctoral theses, graduate theses, undergraduate theses, recent submissions.

The pulse amplifier in theory and experiment 

Optical studies of the nature of metallic surfaces 

A controlled community for Waterbury, Connecticut 

Open Access Theses and Dissertations

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Open Access Theses and Dissertations

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Indexes over 4 million graduate-level electronic theses and dissertations (ETDs) freely available from over 1,100 institutions worldwide . Search for keywords from titles, author names, abstracts, subjects, university/publisher and more. Use More search options to limit searches to a particular field, language, and date range. The search results will include links to full-text theses/dissertations residing on the original hosting site, usually the institutional repository of the school that granted the degree.

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OU theses and dissertations

Online theses.

Are available via Open Research Online .

Print theses

Search for OU theses in the Library Search . To see only print theses click 'In the Walton Hall library' and refine your results to resource type 'Thesis'.

OU staff and research students can  borrow a consultation copy of a thesis (if available). Please contact the Library helpdesk giving the author and title of the thesis.

UK theses and dissertations from EThOS

The Electronic Theses Online System (EThOS) offers free access to the full text of UK theses.

• EThOS offers a one stop online shop providing free access to UK theses
• EThOS digitizes theses on request into PDF format, this may require payment
• EThOS is managed by the British Library in partnership with a number of UK universities
• EThOS is open to all categories of library user

What does this mean to you as a library user?

When you need to access a PhD thesis from another UK based HE institution you should check EThOS to either download a thesis which has already been digitised or to request that a UK thesis be supplied to you.

• For all UK theses EThOS will be the first point of delivery. You can use the online ordering and tracking system direct from EThOS to manage your requests for UK PhD theses, including checking the status of your requests
• As readers you will deal directly with EThOS so will not need to fill in a document delivery request
• OU staff and research students will still be entitled to access non-UK based PhD theses by filling in a document delivery request
• In some cases where EThOS is unable to supply a UK thesis OU staff and research students will be able to access it by filling in a conventional document delivery request. The thesis will be supplied through direct loan
• The EThOS system is both faster and cheaper than the previous British Theses service which was based on microfilm
• The British Library no longer arranges interlibrary loans for UK PhD theses
• Interlibrary Loan procedures for other types of request from the British Library (articles and books for example) will remain the same

If you have any queries about using EThOS contact the Document Delivery Team ( [email protected] or the Library Helpdesk ).

Note 13/03/2024: The British Library is continuing to experience a major technology outage affecting its websites and other online systems, due to a Cyber attack. as a result access to ETHOS might not be possible until the issue is fixed. 

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UBC Theses and Dissertations

Open collections, limit this search.

The UBC Theses and Dissertations collection promotes open and comprehensive access to a significant body of unique knowledge created by graduate students to support further research and for private study. The authors retain copyright ownership and moral rights to their theses. The content of theses may not be re-purposed or exploited for commercial gain without the explicit permission of the authors.

UBC graduate students began submitting their theses online via cIRcle, UBC’s digital repository, in fall 2007, a practice that both simplified the submission process and also ensured the availability of this research to a global audience in a timely manner. As of March 2012, UBC Library has digitized and made openly accessible the full-text of more than 32,000 theses submitted by graduate students between 1919 and 2007. In addition to providing information about specific fields of study these theses also reveal important information about changes in pedagogy at the University and within academic disciplines. Authors concerned about having their pre-2007 theses included as part of this collection can notify [email protected] to have their thesis removed. Similarly, if copyrighted material appears in a thesis the copyright owner can request that material be removed.

Browse Theses & Dissertations

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Browse Dissertations and Electronic Theses

Linguistics Graduate Dissertations ( Department of Linguistics )

Linguistics Undergraduate Senior Essays ( Department of Linguistics )

Masters of Environmental Design Theses ( Yale School of Architecture )

Public Health Theses ( School of Public Health )

Yale Divinity School Theses ( Yale Divinity School )

Yale Graduate School of Arts and Sciences Dissertations

Yale Medicine Thesis Digital Library ( School of Medicine )

Starting with the Yale School of Medicine (YSM) graduating class of 2002, the Cushing/Whitney Medical Library and YSM Office of Student Research have collaborated on the Yale Medicine Thesis Digital Library (YMTDL) project, publishing the digitized full text of medical student theses on the web as a valuable byproduct of Yale student research efforts. The digital thesis deposit has been a graduation requirement since 2006. Starting in 2012, alumni of the Yale School of Medicine were invited to participate in the YMTDL project by granting scanning and hosting permission to the Cushing/Whitney Medical Library, which digitized the Library’s print copy of their thesis or dissertation. A grant from the Arcadia Fund in 2017 provided the means for digitizing over 1,000 additional theses. IF YOU ARE A MEMBER OF THE YALE COMMUNITY AND NEED ACCESS TO A THESIS RESTRICTED TO THE YALE NETWORK, PLEASE MAKE SURE YOUR VPN (VIRTUAL PRIVATE NETWORK) IS ON.

Yale School of Medicine Physician Associate Program Theses ( School of Medicine )

Starting with the Yale Physician Associate (PA) Program’s Class of 2020, the Cushing/Whitney Medical Library and the Yale PA Research Program have collaborated to publish the digitized full text of PA student theses on the web as a valuable byproduct of Yale student research efforts. Please review the Terms & Conditions in the left-hand column in order to avoid copyright infringement.

Yale School of Nursing Digital Theses ( School of Nursing )

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Theses and Dissertations

Theses and Dissertations Available from ProQuest

Full text is available to Purdue University faculty, staff, and students on campus through this site. No login is required.

Off-campus Purdue users may download theses and dissertations by logging into the Libraries' proxy server with your Purdue Career Account. Links to log in to the proxy server directly below the download button of each thesis or dissertation page.

Non-Purdue users, may purchase copies of theses and dissertations from ProQuest or talk to your librarian about borrowing a copy through Interlibrary Loan. (Some titles may also be available free of charge in our Open Access Theses and Dissertations Series, so please check there first.)

Access to abstracts is unrestricted.

Open Access Theses

This series contains theses that students have wished to make openly available. The full content is available to all, although some theses may have embargoes. If an embargo exists the date will be listed instead of the download button. The download button will appear once a thesis is no longer embargoed. To browse a fuller listing of theses from Purdue please visit the Theses and Dissertations Available from ProQuest series.

Open Access Dissertations

This series contains open access dissertations that students have wished to make openly available. The full-text content is available to all, although some theses may have embargoes. If an embargo exists the date will be listed instead of the download button. The download button will appear once a dissertation is no longer embargoed. To browse a fuller listing of dissertations from Purdue please visit the Theses and Dissertations Available from ProQuest series.

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Shodhganga Mirror Site https://sg.inflibnet.ac.in -->

• About Shodhganga
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• AICTE/P& AP/Misc/2022_23.12.2022
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• UGC D.O.No.2-10/2021 (CPP-II)_22.12.2021
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http://shodhganga.inflibnet.ac.in/jspui/handle/10603/ Shodhganga Membership is not for Colleges.

MRPs/PDFs/Fellowships Reports

A reservoir of Indian Theses

The Shodhganga@INFLIBNET Centre provides a platform for research students to deposit their Ph.D. theses and make it available to the entire scholarly community in open access. The repository has the ability to capture, index, store, disseminate and preserve ETDs submitted by the researchers. [Read More]

• Latest Updates

Webinar on "An Overview of Research Ethics & Plagiarism Issues" organized by INFLIBNET Centre on 03 June 2020 at 11.30 AM - 01.00 PM. Registration | Brochure

Webinar on "Introduction to ETDs & Shodhganga / Shodhgangotri" organized by INFLIBNET Centre on 05 June 2020 at 11.30 AM - 01.00 PM. Registration | Brochure

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Three Days Online Advanced Training Programme on Shodhganga and Plagiarism Issues organized by INFLIBNET Centre during 25th - 27th November 2020. More Details || Apply Online

Three Days Training (Offline Mode) on Research Methodology and Ethics: Plagiarism Issues, Reference Management Tools and Altmetrics 10th-12th April, 2023 Registration

Three Days Training Programme on "Research Methodology and Ethics: Plagiarism Issues, Reference Management Tools and Altmetrics" at the INFLIBNET Centre, Gandhinagar during 20-22 May 2024. Registration Download Brochure

5,00,000th Thesis is uploaded into Shodhganga by Prof Yogesh Singh, Hon'ble Chairman, Governing Board, INFLIBNET Centre & Vice Chancellor, University of Delhi, Delhi in the august presence of Prof J P Singh Joorel, Director, INFLIBNET Centre, Gandhinagar and other Governing Board Members on 14.12.2023.

All the Theses (CDs) received from Universities were successfully uploaded into Shodhganga Portal till August 2023.

ETD 2023 website is launched by Hon'ble Chairman of UGC Prof M Jagadesh Kumar on 17-02-2023 at 10.00 AM, in presence of the Director INFLIBNET Centre, other Bureau Heads of UGC, staff of INFLIBNET Centre. Please visit at etd2023.inflibnet.ac.in for more details.

Creation of Metadata and Uploading Theses into Shodhganga for more details

Shodhganga crossed 4,00,000 Theses on 8th December 2022.

IISc Bangalore and 55 CFTIs like IITs,IIMs,NITs etc. have joined Shodhganga.

Restricted Dashboard and Subject Portal is released in January 2020.

Shodhganga crossed 3,00,000 Theses on 9th April 2021.

Plagiarism Detection Software under ShodhShuddhi is provided to all 1000+ Universities/Institutions.

Shodhganga Membership is not for Colleges. Read More.

UGC (Promotion of Academic Integrity and Prevention of Plagiarism in Higher Educational Institutions) Regulations, 2018. UGC Letter / Regulation

The NDLTD Leadership Award 2017 was conferred to Shodhganga Team leaders during August 7 - 9, 2017 at Washington, DC. The Award is instituted by the Networked Digital Library of Theses and Dissertations (NDLTD) since 2004. More Details

Edushine Excellence Award - 2019 presented to INFLIBNET Centre by Sh. Suresh Prabhu, Hon'ble Minister for Commerce & Industry and Civil Aviation, Government of India.

Theses received at the Centre till 30th November 2020 have been uploaded.

750+ Universities started contributing Theses Repository.

865+ Universities+CFTIs/INIs Signed MoU.

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Anna University 15954

University of madras 15006, university of calcutta 14244, savitribai phule pune university 12765, university of mumbai 11589, aligarh muslim university 10293, chhatrapati sahuji maharaj university 10180, andhra university 10082, babasaheb bhimrao ambedkar bihar university 9675, panjab university 9443, abhilashi university 17, academy of scientific and innovative research (acsir) 2630, acharya nagarjuna university 2285, acharya narendra deva university of agriculture and technology, ayodhya 908, adamas university 45, adesh university 25, adichunchanagiri university, mandya 9, adikavi nannaya university, rajahmundry 58, agriculture university, jodhpur 3, agriculture university, kota 13, ahmedabad university 18, aks university 30, alagappa university 2478, alliance university 53, all india institute of medical science, bhopal 1, all india institute of medical sciences rishikesh 7, ambedkar university, delhi 60, amet university 141, amity university haryana 212, amity university, kolkata 2, amity university madhya pradesh 66, amity university, mumbai 32, amity university, noida 1182, amity university rajasthan 232, amrita vishwa vidyapeetham university 604, anand agricultural university 122, annamalai university 3244, apeejay stya university 23, apex university, rajasthan 41, a p goyal shimla university 14, apj abdul kalam technological university, thiruvananthapuram 53, arka jain university 3, arni university 8, arunachal university of studies 2, arunodaya university 2, aryabhatta knowledge university 31, ashoka university 1, assam agricultural university 151, assam don bosco university 123, assam down town university 82, assam rajiv gandhi university of cooperative management 2, assam science and technology university 8, assam university 2297, atal bihari vajpayee indian institute of information technology and management 103, atmiya university 20, auro university 1, avinashilingam institute for home science and higher education for women 723, awadhesh pratap singh university 971, baba ghulam shah badshah university 100, baba mastnath university 80, babasaheb bhimrao ambedkar university 525, babu banarasi das university 148, baddi university of emerging sciences & technology 7, bahra university 5, banaras hindu university 8094, banasthali vidyapith 2213, bangalore university 2500, bankura university 31, bareilly international university 5, barkatullah university 421, bennett university 37, berhampur university 207, bhagat phool singh mahila vishwavidyalaya 140, bhagwan mahavir university 1, bhagwant university 315, bhaikaka university 3, bhakta kavi narsinh mehta university 63, bharathiar university 7394, bharathidasan university 8300, bharath institute of higher education and research 711, bharati vidyapeeth deemed university 652, bhartiya skill development university jaipur 20, bhupendra narayan mandal university 5, bihar agricultural university 89, birla institute of management technology 11, birla institute of technology and science 1630, birla institute of technology, mesra 177, blde (deemed to be university) 54, bml munjal university, gurugram 7, bodoland university 105, brainware university 36, b s abdur rahman crescent institute of science & technology 316, bundelkhand university 2213, calorx teachers university 2, career point university 29, central institute of technology kokrajhar 15, central sanskrit university 351, central university of gujarat 362, central university of haryana 95, central university of himachal pradesh 131, central university of jammu 122, central university of jharkhand 87, central university of karnataka 148, central university of kashmir 253, central university of kerala 173, central university of odisha 36, central university of punjab 190, central university of rajasthan 258, central university of south bihar 39, central university of tamil nadu 118, centurion university of technology and management 72, centurion university of technology and management, vizianagaram 0, cept university 82, chaitanya university, hanamkonda 21, chanakya national law university 1, chandigarh university 136, chandra shekhar azad university of agriculture and technology 119, charotar university of science and technology 169, chaudhary charan singh university 3084, chaudhary devi lal university 281, chaudhary ranbir singh university 19, chaudhary sarwan kumar himachal pradesh krishi vishvavidyalaya 406, chettinad academy of research and education 164, chhatrapati shivaji maharaj university 3, chhattisgarh swami vivekanand technical university 149, childrens university 18, chitkara university 31, chitkara university, punjab 310, christ university 362, cmj university 2, cmr university 51, cochin university of science & technology 2773, cooch behar panchanan barma university 34, cotton university 32, ct university 56, c.u. shah university 200, c.v. raman global university 29, datta meghe institute of medical sciences 208, davangere university 118, dav university 32, dayalbagh educational institute 1231, dayananda sagar university 51, deccan college post graduate and research institute 380, deenbandhu chhotu ram university of science and technology, sonipat 193, deen dayal upadhyay gorakhpur university 841, defence institute of advanced technology 44, delhi pharmaceutical sciences & research university (dpsru) 19, delhi technological university 496, desh bhagat university 246, devi ahilya vishwavidyalaya 2296, dev sanskriti vishwavidyalaya 13, dharmsinh desai university 24, dhirubhai ambani institute of information and communication technology (da-iict) 77, diamond harbour women's university 11, dibrugarh university 966, dit university 94, doon university 55, dr. a.p.j. abdul kalam technical university 409, dravidian university 58, dr. babasaheb ambedkar marathwada university 5569, dr. babasaheb ambedkar open university 186, dr. babasaheb ambedkar technological university 51, dr b r ambedkar national institute of technology jalandhar 109, dr. b. r. ambedkar open university, hyderabad 1, dr. b. r. ambedkar university agra 6008, dr. c.v. raman university 318, dr. d. y. patil vidyapeeth, pune 167, dr. harisingh gour vishwavidhyalay 2300, dr. k n modi university 28, dr. m.g.r. educational and research institute 505, dr. panjabrao deshmukh krishi vidyapeeth, akola 50, dr. rammanohar lohia avadh university, faizabad 4638, dr ram manohar lohiya national law university 58, dr. sarvepalli radhakrishnan rajasthan ayurved university 191, dr shakuntala misra national rehabilitation university 74, dr. shyama prasad mukherjee international institute of information technology naya raipur 9, dr. vishwanath karad mit world peace university 23, dr. y.s. parmar university of horticulture and forestry 177, dr.y.s.r. horticultural university 24, d y patil university, kolhapur 67, entrepreneurship development institute of india 1, eternal university 7, fakir mohan university, balasore 165, forest research institute university 350, galgotias university 88, gangadhar meher university 86, ganpat university 165, garden city university 8, gauhati university 6328, gautam buddha university 240, g.b.pant university of agriculture & technology 172, gd goenka university 124, geetanjali university 44, g h raisoni university, amravati 23, giet university, gunupur 24, gitam university 928, gla university 230, glocal university 93, gls university 123, gna university 27, goa university 1093, gokhale institute of politics and economics 31, gokul global university 3, gondwana university 182, graphic era hill university dehradun 17, graphic era university 155, gujarat ayurveda university 5, gujarat forensic sciences university 26, gujarat national law university 21, gujarat technological university 367, gujarat university 4519, gujarat vidyapith 620, gulbarga university 1127, guru angad dev veterinary and animal sciences university 5, guru ghasidas university 353, guru gobind singh indraprastha university 640, guru jambheshwar university of science & technology 675, guru kashi university 367, gurukul kangri vishwavidyalaya 411, guru nanak dev university 2019, harcourt butler technical university 16, hemchandracharya north gujarat university 572, hemchand yadav vishwavidyalaya 47, hemwati nandan bahuguna garhwal university 950, himachal pradesh national law university 1, himachal pradesh university 3149, himalayan garhwal university 64, himgiri zee university 37, hindustan institute of technology and science 315, homi bhabha national institute 2575, homoeopathy university 26, icfai foundation for higher education, telangana 89, icfai university, dimapur nagaland 25, icfai university himachal pradesh 5, icfai university, jaipur 17, icfai university, jharkhand 45, icfai university, tripura 13, iec university 15, iftm university 297, iilm university, gurugram 13, iimt university, meerut 19, iis (deemed to be university) 413, i k gujral punjab technical university 850, ims unison university 15, indian institute of engineering science and technology, shibpur 450, indian institute of foreign trade 62, indian institute of information technology, allahabad 204, indian institute of information technology, design and manufacturing, iiitdm jabalpur 144, indian institute of information technology design & manufacturing kancheepuram 70, indian institute of information technology dharwad 2, indian institute of information technology guwahati 21, indian institute of information technology kalyani 9, indian institute of information technology nagpur 3, indian institute of informationtechnology, vadodara 1, indian institute of management ahmedabad 15, indian institute of management bangalore 47, indian institute of management (iim),indore 38, indian institute of management kashipur 21, indian institute of management kozhikode 27, indian institute of management lucknow 104, indian institute of management mumbai (formerly nitie) 72, indian institute of management raipur 47, indian institute of management rohtak 6, indian institute of management shillong 16, indian institute of management udaipur 1, indian institute of science bangalore 1207, indian institute of science education and research (iiser) bhopal 39, indian institute of science education and research (iiser) mohali 356, indian institute of science education and research (iiser) pune 521, indian institute of science education and research (iiser) thiruvananthapuram 210, indian institute of science education and research kolkata 105, indian institute of space science and technology 179, indian institute of teacher education 7, indian institute of technology bhilai 17, indian institute of technology bhubaneswar 76, indian institute of technology bombay 1695, indian institute of technology delhi 1884, indian institute of technology dharwad 9, indian institute of technology gandhinagar 39, indian institute of technology goa 3, indian institute of technology guwahati 2507, indian institute of technology hyderabad 290, indian institute of technology iit (bhu), varanasi 985, indian institute of technology indore 399, indian institute of technology (ism), dhanbad 1043, indian institute of technology jammu 20, indian institute of technology jodhpur 149, indian institute of technology kanpur 1, indian institute of technology kharagpur 814, indian institute of technology madras 1608, indian institute of technology mandi 254, indian institute of technology palakkad 16, indian institute of technology patna 148, indian institute of technology roorkee 490, indian institute of technology ropar 204, indian institute of technology tirupati 11, indian maritime university 1, indian school of mines 53, indian veterinary research institute, izatnagar 343, indira gandhi delhi technical university for women 59, indira gandhi institute of development research 105, indira gandhi national open university ignou 976, indira gandhi national tribal university, amarkantak 155, indira gandhi university meerpur,rewari 43, indira kala sangeet vishwavidyalaya 133, indraprastha institute of information technology, delhi (iiit-delhi) 137, indrashil university 4, indus international university 7, indus university 44, institute of advanced research, gandhinagar 14, institute of advanced studies in education (iase) 191, institute of chemical technnology, mumbai 105, institute of infrastructure technology research and management 35, institute of trans-disciplinary health science & technology 32, integral university 614, international institute for population sciences iips 366, international institute of information technology bangalore 66, international institute of information technology, hyderabad 192, international management institute 9, international management institute kolkata 2, invertis university, bareily 1, isbr business school 1, islamic university of science and technology 48, itm university, gwalior 28, jadavpur university 3973, jagadguru ramanadacharya rajasthan sanskrit university 2, jagannath university 212, jagannath university, jhajjar 53, jagran lakecity university 31, jai narain vyas university 590, jain university 754, jain vishwa bharati university 246, jai prakash vishwavidyalaya 3, jaipur national university 349, jamia hamdard university 939, jamia milia islamia university 2514, janardan rai nagar rajasthan vidhyapeeth 1, jawaharlal nehru architecture and fine arts university 7, jawaharlal nehru centre for advanced scientific research 42, jawaharlal nehru technological university, anantapuram 1317, jawaharlal nehru technological university, hyderabad 1468, jawaharlal nehru technological university, kakinada 310, jawaharlal nehru university 7423, jayoti vidyapeeth women s university 327, jaypee institute of information technology 336, jaypee university of engineering & technology, guna 122, jaypee university of information technology, solan 278, j. c. bose university of science and technology, ymca, faridabad 64, jecrc university 88, jharkhand rai university 48, jis university, kolkata 18, jiwaji university 2316, jk lakshmipat university 22, jodhpur national university 2, jss academy of higher education & research 403, jss science and technology university, mysuru 22, j.s. university, shikohabad 26, junagadh agricultural university 1, kadi sarva vishwavidyalaya 594, kakatiya university, warangal 532, kalasalingam university 406, kalinga institute of social sciences (kiss) 8, kalinga university 238, kamdhenu university 8, kameshwara singh darbhanga sanskrit vishwavidyalaya, darbhanga 3, kannada university 101, kannur university 879, karnataka samskrit university 61, karnataka state law university 12, karnataka state open university 17, karnataka state womens university 297, karnataka veterinary, animal and fisheries sciences university 102, karnatak university 5113, karnavati university 11, karpagam university 298, karunya university 582, kavayitri bahinabai chaudhari north maharashtra university 1278, kavikulaguru kalidas sanskrit university 149, kazi nazrul university 24, kerala agricultural university 9, kerala university of health sciences 2, khwaja moinuddin chishti urdu, arabi-farsi university 16, kiit university 1077, king george medical university 21, kle technological university 13, kle university 187, kolhan university 34, koneru lakshmaiah education foundation 931, krantiguru shyamji krishna verma kachchh university 124, krea university 1, krishna institute of medical sciences, deemed to be university karad 68, krishna kanta handiqui state open university 36, krishna university, machilipatnam 69, k.r. mangalam university, gurgaon 101, kumaun university 1719, kurukshetra university 1483, kushabhau thakre patrakarita avam jansanchar vishwavidyalaya 7, kuvempu university 1388, lakshmibai national university of physical education 221, lakulish yoga university 19, lalit narayan mithila university 6859, lingayas vidyapeeth 94, lnct university 136, lovely professional university 831, madan mohan malaviya university of technology 91, madhav university 241, madhyanchal professional university 3, madhya pradesh bhoj (open) university 9, madurai kamaraj university 5837, magadh university 22, mahapurusha srimanta sankaradeva viswavidyalaya 38, maharaja agrasen university 105, maharaja ganga singh university 2278, maharaja krishnakumarsinhji bhavnagar university 1506, maharaja ranjit singh punjab technical university 19, maharaja sayajirao university of baroda 4071, maharaja sriram chandra bhanja deo university 16, maharaja vinayak global university 107, maharana pratap university of agriculture and technology 158, maharashtra animal and fishery sciences university 17, maharashtra national law university nagpur 5, maharashtra university of health sciences 221, maharishi markandeshwar university, mullana 505, maharishi markandeshwar university, sadopur (ambala) 27, maharishi university of information technology 50, maharshi dayanand saraswati university 209, maharshi dayanand university 4652, mahatma gandhi antarrashtriya hindi vishwavidyalaya 254, mahatma gandhi chitrakoot gramodaya vishwavidyalaya 148, mahatma gandhi kashi vidyapith 4972, mahatma gandhi univeristy of medical sciences & technnology , jaipur 39, mahatma gandhi university 3942, mahatma gandhi university, nalgonda 13, mahatma jyotiba phule rohilkhand university 1657, makhanlal chaturvedi national university of journalism and communication, bhopal 22, malaviya national institute of technology jaipur 361, malwanchal university, indore 44, management development institute gurgaon 25, manav rachna international institute of research and studies 228, manav rachna university 58, mandsaur university 56, mangalayatan university 122, mangalore university 2021, manipal academy of higher education 1699, manipal university jaipur 316, manipur university 1813, manonmaniam sundaranar university 7400, martin luther christian university 43, marwadi university 15, mats university 89, maulana abul kalam azad university of technology 85, maulana azad national institute of technology bhopal 282, maulana azad national urdu university 391, m.b.m. university 15, medi caps university, indore 25, meenakshi academy of higher education and research 167, mewar university 335, mgm institute of health sciences 134, mica, ahmedabad 26, mit-adt university, pune 51, mizoram university 783, mody university of science and technology 120, mohammad ali jauhar university 4, mohan lal sukhadia university 1053, monad university 36, motherhood university 1, mother teresa womens university 1071, motilal nehru national institute of technology 578, m s ramaiah university of applied sciences 70, mvn university,palwal 69, nagaland university 520, narsee monjee institute of management studies 279, national brain research centre 97, national institute of educational planning and administration (niepa) 34, national institute of fashion technology delhi 30, national institute of food technology entrepreneurship and management - niftem (k)kundli 25, national institute of food technology entrepreneurship and management thanjavur (niftem-t) 27, national institute of pharmaceutical education and research, ahmedabad 29, national institute of pharmaceutical education and research, guwahati 24, national institute of pharmaceutical education and research, hajipur 11, national institute of pharmaceutical education and research, hyderabad 41, national institute of pharmaceutical education and research kolkata 14, national institute of pharmaceutical education and research, raebareli 6, national institute of technology agartala 173, national institute of technology arunachal pradesh 54, national institute of technology calicut 228, national institute of technology delhi 67, national institute of technology durgapur 160, national institute of technology goa 49, national institute of technology hamirpur 94, national institute of technology jamshedpur 122, national institute of technology karnataka 494, national institute of technology,kurukshetra 158, national institute of technology manipur 72, national institute of technology mizoram 34, national institute of technology nagaland 11, national institute of technology (nit) meghalaya 96, national institute of technology (nit), warangal 555, national institute of technology patna 344, national institute of technology puducherry 56, national institute of technology raipur 192, national institute of technology, rourkela 398, national institute of technology sikkim 29, national institute of technology silchar 69, national institute of technology srinagar 189, national institute of technology tiruchirappalli 234, national institute of technology uttarakhand 35, national law institute university, bhopal 8, national law school of india university 48, national law university and judicial academy, guwahati 9, national law university, delhi 37, national law university, odisha 12, national museum institute of hisotry of art conservation and musicology 2, national sanskrit university 47, navrachana university 24, nehru gram bharati university 155, netaji subhas open university 1, netaji subhas university of technology 9, niilm university 1, niit university 15, nims university rajasthan 358, nirma university 383, nitte university 94, noida international university 77, noorul islam centre for higher education 351, north-eastern hill university 2730, north eastern regional institute of science and technology (nerist) 95, odisha university of agriculture and technology 160, om sterling global university 100, o.p. jindal university 8, opjs university 21, oriental university 92, osmania university 1638, pacific university 2297, padmashree dr. d.y. patil vidyapeeth, navi mumbai 74, pandit deendayal petroleum university 176, pandit s. n. shukla university, shahdol 10, parul university 190, patna university 332, peoples university, bhopal 7, periyar maniammai university 157, periyar university 3257, pes university 23, p.k. university 24, pondicherry university 2509, poornima university 75, potti sreeramulu telugu university 1, p p savani university 3, pravara institute of medical sciences 45, presidency university 108, presidency university, karnataka 155, prist university 86, pt. ravishankar shukla university 2918, pt. sundarlal sharma open university bilaspur 250, punjab engineering college (deemed to be university) 60, punjabi university 3180, rabindra bharati university 421, rabindranath tagore university, bhopal 321, raffles university 16, raiganj university 182, rai university 308, rajasthan technical university, kota 149, rajiv gandhi institute of petroleum technology 37, rajiv gandhi national institute of youth development 7, rajiv gandhi national university of law punjab 31, rajiv gandhi proudyogiki vishwavidyalaya 598, rajiv gandhi university 655, rama devi womens university 12, ramakrishna mission vivekananda educational and research institute 222, ramakrishna mission vivekananda university 1, rama university, uttar pradesh 74, ramchandra chandravansi university 7, ranchi university 91, rani channamma university 118, rani durgavati vishwavidyalaya 356, rashtrasant tukadoji maharaj nagpur university 311, rashtriya raksha university 19, ravenshaw university 486, rayat bahra university, mohali 16, regional centre for biotechnology 1, reva university 219, rimt university 38, rkdf university 126, rk university 287, rnb global university 4, sage university, indore 82, sai nath university 138, sambalpur university 1774, sam higginbottom institute of agriculture, technology and sciences 478, sampurnanand sanskrit vishwavidhyalaya 3, sanchi university of buddhist-indic studies, bhopal 6, sandip university 39, sangam university 63, sanjay gandhi post graduate institute of medical sciences, lucknow 12, sanjay ghodawat university 2, sankalchand patel university 54, sanskriti university 49, sant baba bhag singh university 38, sant gadge baba amravati university 3025, sant longowal institute of engineering and technology 315, santosh deemed to be university 104, sardarkrushinagar dantiwada agricultural university 0, sardar patel university 3350, sardar vallabhbhai national institute of technology surat 409, sarvepalli radhakrishnan university 148, sastra university 553, satavahana university 8, sathyabama institute of science and technology 422, saurashtra university 3277, saveetha university 836, school of planning and architecture, bhopal 21, school of planning and architecture, new delhi 49, school of planning and architecture vijayawada 10, seacom skills university 116, sgt university 105, sharda university 215, sher-e-kashmir university of agricultural sciences and technology of jammu 137, shivaji university 4872, shiv nadar university 176, shobhit university, gangoh 29, shobhit university, meerut 166, shoolini university of biotechnology and management sciences 511, shree somnath sanskrit university 110, shri govind guru university 24, shri guru ram rai university 60, shri jagdishprasad jhabarmal tibarewala university 3652, shri khushal das university 117, shri lal bahadur shastri national sanskrit university 545, shri mata vaishno devi university 227, shri ramswaroop memorial university 150, shri vaishnav vidyapeeth vishwavidyalaya 47, shri venkateshwara university, uttar pradesh 2, shyam university 9, sidho kanho birsha university 106, sido kanhu murmu university 21, sikkim manipal university 87, sikkim university 206, siksha "o" anusandhan university 568, singhania university 23, sir padampat singhania university 75, sndt womens university 1263, solapur university 270, south asian university 2, s. p. jain institute of management and research 1, sree sankaracharya university of sanskrit 719, sri balaji vidyapeeth 53, sri chandrasekharendra saraswathi viswa mahavidyalaya 417, sri devaraj urs academy of higher education and research 43, sri guru granth sahib world university 84, sri guru ram das university of health sciences 9, sri krishnadevaraya university 3434, srinivas university 17, sri padmavathi womens university 245, sri ramachandra institute of higher education and research 372, sri sai university 2, sri sathya sai institute of higher learning 110, sri satya sai university of technology & medical sciences 80, sri siddhartha academy of higher education 59, sri sri university 17, sri venkateswara institute of medical sciences 23, sri venkateswara university 5461, srm institute of science and technology 1561, srm university- ap 21, srm university, delhi-ncr, sonepat 83, starex university 2, st. joseph university, dimapur 14, st. peter’s institute of higher education and research 394, st. xaviers university, kolkata 1, sumandeep vidyapeeth deemed to be university 48, sunrise university 5, suresh gyan vihar university 387, sushant university (earlier ansal university) 59, swami rama himalayan university 14, swami ramanand teerth marathwada university 5618, swami vivekanad subharti university 178, swami vivekananda yoga anusandhana sansthana 142, swami vivekanand university 80, swarnim gujarat sports university 7, symbiosis international university 515, tamil nadu agricultural university 1415, tamil nadu dr. ambedkar law university 59, tamil nadu open university 49, tamilnadu physical education and sports university 259, tamil nadu teachers education university, chennai 203, tamil nadu veterinary and animal sciences university 79, tamil university 161, tantia university 240, tata institute of fundamental research 1008, tata institute of social sciences 583, techno india university 4, teerthanker mahaveer university 132, teri school of advanced studies 138, tezpur university 912, thapar institute of engineering and technology 1198, the assam kaziranga university 23, the assam royal global university 14, the charutar vidya mandal cvm university 5, the english & foreign languages university, hyderabad 786, the gandhigram rural institute 1374, the icfai university, dehradun 42, the iihmr university, jaipur 35, the indian law institute, new delhi 19, the lnm institute of information technology 34, the national academy of legal studies and research (nalsar) university of law 50, the national university of advanced legal studies 4, the neotia university 4, the northcap university 109, the tamil nadu dr. m.g.r. medical university 421, the university of burdwan 3079, the west bengal national university of juridical sciences 35, thiruvalluvar university 289, thunchath ezhuthachan malayalam university 16, tilak maharashtra vidyapeeth 910, tilka manjhi bhagalpur university 269, tripura university 446, tumkur university 299, uka tarsadia university 113, university of agricultural sciences, bangalore 453, university of agricultural sciences, dharwad 286, university of agricultural sciences, raichur 63, university of allahabad 2509, university of calicut 2233, university of delhi 5326, university of engineering and management, kolkata 17, university of gour banga 12, university of hyderabad 2703, university of jammu 1202, university of kalyani 2836, university of kashmir 1927, university of kerala 6838, university of kota 113, university of lucknow 6079, university of mysore 4302, university of north bengal 2072, university of patanjali 32, university of petroleum and energy studies (upes) 398, university of rajasthan 1810, university of science and technology, meghalaya 101, u.p. pt. deen dayal upadhyaya pashu chikitsa vigyan vishwavidhyalaya evam go anusandha sansthan 18, u p rajarshi tondon open university 336, usha martin university 21, utkal university 5661, uttarakhand open university 18, uttarakhand sanskrit university 56, uttarakhand technical university 275, uttaranchal university 73, vardhaman mahaveer open university, kota 21, v. b. s. purvanchal university 9113, veer kunwar singh university, arrah 32, veer narmad south gujarat university 3353, veer surendra sai university of technology 189, vellore institute of technology bhopal 8, vellore institute of technology, vellore 2273, vellore institute of technology (vit-ap) 72, vels university 913, vel tech rangarajan dr. sagunthala r&d institute of science and technology 236, vidyasagar university 881, vignans foundation for science technology and research 211, vijayanagara sri krishnadevaraya university, bellary 131, vikram university 95, vinayaka missions research foundation 361, vinoba bhave university 248, vishwakarma university 27, visva bharti university 1582, visvesvaraya national institute of technology 283, visvesvaraya technological university, belagavi 1064, vivekananda global university 74, william carey university 1, xim university 26, yashwantrao chavan maharashtra open university 330, ybn university 41, yenepoya (deemed to be university) 135, yogi vemana university 92, about shodhshuddhi.

Based on the recommendation of Sub-Committee, National Steering Committee (NSC) of e-ShodhSindhu, The Ministry of Education, Govt. of India has initiated a programme "ShodhShuddhi" which provides access to Plagiarism Detection Software (PDS) to all universities/Institutions in India since Sept 1, 2019 [Read More...]

Under this initiative, URKUND a Web Based Plagiarism Detection Software system is being provided to all users of universities/Intuitions in the country. This initiative is formally launched by Honorable Minister of HRD (now renamed as Minister of Education) on September 21, 2019

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Philosophy Theses and Dissertations

Theses/dissertations from 2023 2023.

Karl Marx on Human Flourishing and Proletarian Ethics , Sam Badger

The Ontological Grounds of Reason: Psychologism, Logicism, and Hermeneutic Phenomenology , Stanford L. Howdyshell

Theses/Dissertations from 2022 2022

Interdisciplinary Communication by Plausible Analogies: the Case of Buddhism and Artificial Intelligence , Michael Cooper

Heidegger and the Origin of Authenticity , John J. Preston

Theses/Dissertations from 2021 2021

Hegel and Schelling: The Emptiness of Emptiness and the Love of the Divine , Sean B. Gleason

Nietzsche on Criminality , Laura N. McAllister

Learning to be Human: Ren 仁, Modernity, and the Philosophers of China's Hundred Days' Reform , Lucien Mathot Monson

Nietzsche and Eternal Recurrence: Methods, Archives, History, and Genesis , William A. B. Parkhurst

Theses/Dissertations from 2020 2020

Orders of Normativity: Nietzsche, Science and Agency , Shane C. Callahan

Humanistic Climate Philosophy: Erich Fromm Revisited , Nicholas Dovellos

This, or Something like It: Socrates and the Problem of Authority , Simon Dutton

Climate Change and Liberation in Latin America , Ernesto O. Hernández

Anorexia Nervosa and Bulimia Nervosa as Expressions of Shame in a Post-Feminist , Emily Kearns

Nostalgia and (In)authentic Community: A Bataillean Answer to the Heidegger Controversy , Patrick Miller

Cultivating Virtue: A Thomistic Perspective on the Relationship Between Moral Motivation and Skill , Ashley Potts

Identity, Breakdown, and the Production of Knowledge: Intersectionality, Phenomenology, and the Project of Post-Marxist Standpoint Theory , Zachary James Purdue

Theses/Dissertations from 2019 2019

The Efficacy of Comedy , Mark Anthony Castricone

William of Ockham's Divine Command Theory , Matthew Dee

Heidegger's Will to Power and the Problem of Nietzsche's Nihilism , Megan Flocken

Abelard's Affective Intentionalism , Lillian M. King

Anton Wilhelm Amo's Philosophy and Reception: from the Origins through the Encyclopédie , Dwight Kenneth Lewis Jr.

"The Thought that we Hate": Regulating Race-Related Speech on College Campuses , Michael McGowan

A Historical Approach to Understanding Explanatory Proofs Based on Mathematical Practices , Erika Oshiro

From Meaningful Work to Good Work: Reexamining the Moral Foundation of the Calling Orientation , Garrett W. Potts

Reasoning of the Highest Leibniz and the Moral Quality of Reason , Ryan Quandt

Fear, Death, and Being-a-problem: Understanding and Critiquing Racial Discourse with Heidegger’s Being and Time , Jesús H. Ramírez

The Role of Skepticism in Early Modern Philosophy: A Critique of Popkin's "Sceptical Crisis" and a Study of Descartes and Hume , Raman Sachdev

How the Heart Became Muscle: From René Descartes to Nicholas Steno , Alex Benjamin Shillito

Autonomy, Suffering, and the Practice of Medicine: A Relational Approach , Michael A. Stanfield

The Case for the Green Kant: A Defense and Application of a Kantian Approach to Environmental Ethics , Zachary T. Vereb

Theses/Dissertations from 2018 2018

Augustine's Confessiones : The Battle between Two Conversions , Robert Hunter Craig

The Strategic Naturalism of Sandra Harding's Feminist Standpoint Epistemology: A Path Toward Epistemic Progress , Dahlia Guzman

Hume on the Doctrine of Infinite Divisibility: A Matter of Clarity and Absurdity , Wilson H. Underkuffler

Climate Change: Aristotelian Virtue Theory, the Aidōs Response and Proper Primility , John W. Voelpel

The Fate of Kantian Freedom: the Kant-Reinhold Controversy , John Walsh

Time, Tense, and Ontology: Prolegomena to the Metaphysics of Tense, the Phenomenology of Temporality, and the Ontology of Time , Justin Brandt Wisniewski

Theses/Dissertations from 2017 2017

A Phenomenological Approach to Clinical Empathy: Rethinking Empathy Within its Intersubjective and Affective Contexts , Carter Hardy

From Object to Other: Models of Sociality after Idealism in Gadamer, Levinas, Rosenzweig, and Bonhoeffer , Christopher J. King

Humanitarian Military Intervention: A Failed Paradigm , Faruk Rahmanovic

Active Suffering: An Examination of Spinoza's Approach to Tristita , Kathleen Ketring Schenk

Cartesian Method and Experiment , Aaron Spink

An Examination of John Burton’s Method of Conflict Resolution and Its Applicability to the Israeli-Palestinian Conflict , John Kenneth Steinmeyer

Speaking of the Self: Theorizing the Dialogical Dimensions of Ethical Agency , Bradley S. Warfield

Changing Changelessness: On the Genesis and Development of the Doctrine of Divine Immutability in the Ancient and Hellenic Period , Milton Wilcox

Theses/Dissertations from 2016 2016

The Statue that Houses the Temple: A Phenomenological Investigation of Western Embodiment Towards the Making of Heidegger's Missing Connection with the Greeks , Michael Arvanitopoulos

An Exploratory Analysis of Media Reporting of Police Involved Shootings in Florida , John L. Brown

Divine Temporality: Bonhoeffer's Theological Appropriation of Heidegger's Existential Analytic of Dasein , Nicholas Byle

Stoicism in Descartes, Pascal, and Spinoza: Examining Neostoicism’s Influence in the Seventeenth Century , Daniel Collette

Phenomenology and the Crisis of Contemporary Psychiatry: Contingency, Naturalism, and Classification , Anthony Vincent Fernandez

A Critique of Charitable Consciousness , Chioke Ianson

writing/trauma , Natasha Noel Liebig

Leibniz's More Fundamental Ontology: from Overshadowed Individuals to Metaphysical Atoms , Marin Lucio Mare

Violence and Disagreement: From the Commonsense View to Political Kinds of Violence and Violent Nonviolence , Gregory Richard Mccreery

Kant's Just War Theory , Steven Charles Starke

A Feminist Contestation of Ableist Assumptions: Implications for Biomedical Ethics, Disability Theory, and Phenomenology , Christine Marie Wieseler

Theses/Dissertations from 2015 2015

Heidegger and the Problem of Modern Moral Philosophy , Megan Emily Altman

The Encultured Mind: From Cognitive Science to Social Epistemology , David Alexander Eck

Weakness of Will: An Inquiry on Value , Michael Funke

Cogs in a Cosmic Machine: A Defense of Free Will Skepticism and its Ethical Implications , Sacha Greer

Thinking Nature, "Pierre Maupertuis and the Charge of Error Against Fermat and Leibniz" , Richard Samuel Lamborn

John Duns Scotus’s Metaphysics of Goodness: Adventures in 13th-Century Metaethics , Jeffrey W. Steele

A Gadamerian Analysis of Roman Catholic Hermeneutics: A Diachronic Analysis of Interpretations of Romans 1:17-2:17 , Steven Floyd Surrency

A Natural Case for Realism: Processes, Structures, and Laws , Andrew Michael Winters

Theses/Dissertations from 2014 2014

Leibniz's Theodicies , Joseph Michael Anderson

Aeschynē in Aristotle's Conception of Human Nature , Melissa Marie Coakley

Ressentiment, Violence, and Colonialism , Jose A. Haro

It's About Time: Dynamics of Inflationary Cosmology as the Source of the Asymmetry of Time , Emre Keskin

Time Wounds All Heels: Human Nature and the Rationality of Just Behavior , Timothy Glenn Slattery

Theses/Dissertations from 2013 2013

Nietzsche and Heidegger on the Cartesian Atomism of Thought , Steven Burgess

Embodying Social Practice: Dynamically Co-Constituting Social Agency , Brian W. Dunst

Subject of Conscience: On the Relation between Freedom and Discrimination in the Thought of Heidegger, Foucault, and Butler , Aret Karademir

Climate, Neo-Spinozism, and the Ecological Worldview , Nancy M. Kettle

Eschatology in a Secular Age: An Examination of the Use of Eschatology in the Philosophies of Heidegger, Berdyaev and Blumenberg , John R. Lup, Jr.

Navigation and Immersion of the American Identity in a Foreign Culture to Emergence as a Culturally Relative Ambassador , Lee H. Rosen

Theses/Dissertations from 2012 2012

A Philosophical Analysis of Intellectual Property: In Defense of Instrumentalism , Michael A. Kanning

A Commentary On Gottfried Wilhelm Leibniz's Discourse on Metaphysics #19 , Richard Lamborn Samuel Lamborn

Sellars in Context: An Analysis of Wilfrid Sellars's Early Works , Peter Jackson Olen

The New Materialism: Althusser, Badiou, and Zizek , Geoffrey Dennis Pfeifer

Structure and Agency: An Analysis of the Impact of Structure on Group Agents , Elizabeth Kaye Victor

Moral Friction, Moral Phenomenology, and the Improviser , Benjamin Scott Young

Theses/Dissertations from 2011 2011

The Virtuoso Human: A Virtue Ethics Model Based on Care , Frederick Joseph Bennett

The Existential Compromise in the History of the Philosophy of Death , Adam Buben

Philosophical Precursors to the Radical Enlightenment: Vignettes on the Struggle Between Philosophy and Theology From the Greeks to Leibniz With Special Emphasis on Spinoza , Anthony John Desantis

The Problem of Evil in Augustine's Confessions , Edward Matusek

The Persistence of Casuistry: a Neo-premodernist Approach to Moral Reasoning , Richard Arthur Mercadante

Theses/Dissertations from 2010 2010

Dewey's Pragmatism and the Great Community , Philip Schuyler Bishop

Unamuno's Concept of the Tragic , Ernesto O. Hernandez

Rethinking Ethical Naturalism: The Implications of Developmental Systems Theory , Jared J.. Kinggard

From Husserl and the Neo-Kantians to Art: Heidegger's Realist Historicist Answer to the Problem of the Origin of Meaning , William H. Koch

Queering Cognition: Extended Minds and Sociotechnologically Hybridized Gender , Michele Merritt

Hydric Life: A Nietzschean Reading of Postcolonial Communication , Elena F. Ruiz-Aho

Descartes' Bête Machine, the Leibnizian Correction and Religious Influence , John Voelpel

Aretē and Physics: The Lesson of Plato's Timaeus , John R. Wolfe

Theses/Dissertations from 2009 2009

Praxis and Theōria : Heidegger’s “Violent” Interpretation , Megan E. Altman

On the Concept of Evil: An Analysis of Genocide and State Sovereignty , Jason J. Campbell

The Role of Trust in Judgment , Christophe Sage Hudspeth

Truth And Judgment , Jeremy J. Kelly

The concept of action and responsibility in Heidegger's early thought , Christian Hans Pedersen

Roots and Role of the Imagination in Kant: Imagination at the Core , Michael Thompson

Theses/Dissertations from 2008 2008

Peirce on the Passions: The Role of Instinct, Emotion, and Sentiment in Inquiry and Action , Robert J. Beeson

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Title: facilitating opinion diversity through hybrid nlp approaches.

Abstract: Modern democracies face a critical issue of declining citizen participation in decision-making. Online discussion forums are an important avenue for enhancing citizen participation. This thesis proposal 1) identifies the challenges involved in facilitating large-scale online discussions with Natural Language Processing (NLP), 2) suggests solutions to these challenges by incorporating hybrid human-AI technologies, and 3) investigates what these technologies can reveal about individual perspectives in online discussions. We propose a three-layered hierarchy for representing perspectives that can be obtained by a mixture of human intelligence and large language models. We illustrate how these representations can draw insights into the diversity of perspectives and allow us to investigate interactions in online discussions.

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• The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon
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• http://orcid.org/0000-0002-3539-5351 David S Pisetsky 1 , 2 ,
• http://orcid.org/0000-0002-0093-1572 Alan Herbert 3
• 1 Duke University Medical Center , Durham , North Carolina , USA
• 2 Medical Research , Durham VA Health Care System , Durham , North Carolina , USA
• 3 InsideOutBio Inc , Charlestown , Massachusetts , USA
• Correspondence to Dr David S Pisetsky, Duke University Medical Center, Medical Research Service, Durham, North Carolina, USA; david.pisetsky{at}duke.edu

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by antibodies to DNA (anti-DNA) and other nuclear macromolecules. Anti-DNA antibodies are markers for classification and disease activity and promote pathogenesis by forming immune complexes that deposit in the tissue or stimulate cytokine production. Studies on the antibody response to DNA have focused primarily on a conformation of DNA known as B-DNA, the classic right-handed double helix. Among other conformations of DNA, Z-DNA is a left-handed helix with a zig-zag backbone; hence, the term Z-DNA. Z-DNA formation is favoured by certain base sequences, with the energetically unfavourable flip from B-DNA to Z-DNA dependent on conditions. Z-DNA differs from B-DNA in its immunogenicity in animal models. Furthermore, anti-Z-DNA antibodies, but not anti-B-DNA antibodies, can be present in otherwise healthy individuals. In SLE, antibodies to Z-DNA can occur in association with antibodies to B-DNA as a cross-reactive response, rising and falling together. While formed transiently in chromosomal DNA, Z-DNA is stably present in bacterial biofilms; biofilms can provide protection against antibiotics and other challenges including elements of host defence. The high GC content of certain bacterial DNA also favours Z-DNA formation as do DNA-binding proteins of bacterial or host origin. Together, these findings suggest that sources of Z-DNA can enhance the immunogenicity of DNA and, in SLE, stimulate the production of cross-reactive antibodies that bind both B-DNA and Z-DNA. As such, DNA can act as a molecular chameleon that, when stabilised in the Z-DNA conformation, can drive autoimmunity.

• Autoantibodies
• Autoimmunity
• Lupus Erythematosus, Systemic

https://doi.org/10.1136/ard-2023-225266

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Introduction

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by inflammatory disease manifestations in association with antibodies to components of the cell nucleus (antinuclear antibodies (ANAs)). 1 These antibodies can bind to DNA, RNA as well as protein-nucleic acid complexes. ANA expression is so linked with SLE that a positive test for these antibodies is now required for disease classification. 2 3 According to the current model for SLE, ANAs can bind to their cognate antigens to form immune complexes with two main actions: deposition in the kidney to induce nephritis and stimulation of aberrant cytokine production by interaction of the constituent DNA or RNA with internal nucleic acid sensors. 4

Among ANAs expressed in SLE, antibodies to DNA (anti-DNA) are unique since they are markers for both classification and disease activity. 5–7 A large negatively charged polymer, DNA displays a repeating structure marked by the helical twist of the phosphodiester backbone ( figure 1 ). The main conformation of DNA is called B-DNA. B-DNA is the classic Watson-Crick right-handed double helix with two chains bound together by hydrogen bonds to form a smooth helix with a major and minor groove. Since anti-DNA antibodies from patients with SLE can bind to essentially any natural double stranded DNA, the phosphodiester backbone appears to be the relevant antigenic structure.

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DNA chameleon colours. Left-handed Z-DNA has a zig-zag backbone resulting from the dinucleotide repeat with alternating syn- and anti -bases. In contrast, the backbone of right-handed B-DNA is smooth as all the bases have an anti -conformation. The phosphate oxygens are red, the phosphorous atoms orange and the grey spheres represent deoxyribose carbons. The small blue circles are base nitrogens while the small red circles base oxygens. The backbone atoms are enlarged to highlight the differences between B-DNA and Z-DNA.

Modelling anti-DNA production by immunisation of animals with B-DNA has in general been unsuccessful, even with DNA bound to protein carriers such as methylated bovine serum albumin and administered in adjuvant; other carriers, however, may lead to more robust responses. 8 9 The poor immunogenicity of B-DNA has been a conundrum since monoclonal anti-B-DNA from patients or mice with lupus-like disease have the hallmarks of antigen selection by negatively charged DNA (ie, variable region somatic mutations leading to positively charged amino acids such as arginine). 10 11 The failure to establish an induced model of SLE has even suggested that a molecule other than DNA induces anti-DNA production.

As now recognised, DNA can exist in conformations other than B-DNA; in the genome, these conformations can arise from sequences called flipons. 12 13 These non-B-DNA conformations, which depend on base sequence and ambient conditions, differ in the orientation and dimensions of the helix. This review will focus on the unique properties of a conformation known as Z-DNA and advance the idea that DNA can act as a molecular chameleon whose structure and immunological properties can dramatically change. A chameleon is a small lizard that can change its colour depending on the surroundings. By considering DNA as a molecular chameleon, we believe that new insights into the immune response to DNA can be achieved, thereby illuminating the pathogenesis of SLE.

The structure of DNA

The double helix has been called a beautiful molecule because its structure can account so elegantly for its role in heredity. From the time that the original Watson-Crick model was first proposed, structural studies indicated that DNA can adopt conformations other than right-handed B-DNA, each just as beautiful. Indeed, the first crystal structure of double-stranded DNA showed a helical twist to the left rather than to the right. 14 Instead of being smooth as in B-DNA, the backbone in this structure had a zig-zag configuration that gave rise to the name of Z-DNA ( figure 1 ).

The structure of Z-DNA shows a two base pair repeat, alternating between a nucleotide in the syn conformation (with its base pointing back over the sugar) and the anti conformation (with the base pointing away from the sugar as found in B-DNA). 15–17 Also, in Z-DNA, the base pairs are flipped over relative to that of B-DNA, with the flip in conformation occurring without breaks in the DNA backbone. 16 18 19 The transition is dynamic and rapid, with Z-DNA formation requiring an input of energy, mostly to initiate the formation of the two junctions between B-DNA and Z-DNA (BZj). The likelihood of a flip to Z-DNA depends on base sequence, with alternating GC sequences converting to Z-DNA more readily. Like DNA, RNA can form a Z structure that depends on sequence; Z-DNA and Z-RNA can be bound by the same proteins, including antibodies, and both are designated as Z nucleic acids.

In model studies in vitro, the flip from B-DNA to Z-DNA is influenced by a variety of factors that include the salt concentration, with 4 M NaCl or 1 M MgCl 2 needed to induce the Z-DNA conformation in Z-prone polymers. Chemical modifications of DNA bases can also promote the B-DNA to Z-DNA transition under more physiological conditions by stabilising the Z-DNA syn conformation. These modifications include bromination, methylation and oxidation. 20–23 Many biochemical and immunochemical studies to elucidate Z-DNA-dependent outcomes have used the compound brominated poly(dGdC) [Br-poly(dGdC)] as a model substrate since the polymer is locked in the Z-DNA conformation under ordinary salt conditions as shown by analysis of circular dichroism and the ratio of 260 to 295 nm UV absorbances. 22

The structure of Z-DNA and the conditions needed for its induction differ so greatly from those of B-DNA that its biological role (and even its existence inside cells) was long debated. Increasing data, however, support the relevance of Z-DNA to in vivo cell function. As discussed in recent reviews, the transition to non-B-DNA conformations such as Z-DNA can occur under physiological conditions to regulate gene transcription. 15 24 Supercoiling induced by the action of RNA polymerases can promote the B to Z transition during transcription; in this setting, the flip can be modulated by methylation and other base modifications. Enzymes like topoisomerases can also affect the transition. 24 25

The antibody response to Z-DNA

Unlike B-DNA, Z-DNA is an effective immunogen and can potently induce antibodies by immunisation of normal animals under conditions in which B-DNA is inactive. 20 26–28 Anti-Z-DNA antibodies induced by immunisation with compounds such as Br-poly(dGdC) are highly specific for Z-DNA and bind by non-ionic interactions since binding occurs in high salt conditions. At least some of the antibodies to Z-DNA induced by immunisation appear to recognise sequences, likely binding to base residues ordinarily buried in the major groove of B-DNA but exposed on the convex surface of Z-DNA. 28

The immunogenicity of Z-DNA as revealed in immunisation models has suggested that Z-DNA may not induce canonical B cell tolerance through deletion or anergy because of its transience or low concentrations. In contrast, B-DNA is both ubiquitous and abundant and may therefore involve different mechanisms of central and peripheral B cell tolerance than Z-DNA. While tolerance to DNA is a topic of ongoing investigations, nevertheless, the differences between antibody induction by B-DNA and Z-DNA are nevertheless striking.

In addition to immunisation of animals, the expression of anti-Z-DNA occurs in SLE. 29–33 Sera of patients with SLE display levels of anti-Z-DNA antibodies that are similar to those to B-DNA when measured using synthetic Z-DNA antigens (eg, Br-poly(dGdC)). Furthermore, antibodies to both B-DNA and Z-DNA conformations can rise and fall together, suggesting common induction or cross-reactivity ( figure 2 ). 29 32 Affinity adsorption experiments indicate that certain anti-DNA antibodies in SLE can bind both B-DNA and Z-DNA, while others are specific for Z-DNA. 29 32 While antibodies to Z-DNA were initially described almost 40 years ago, it was not clear until recently how to interpret this discovery.

Longitudinal expression of antibodies to B-DNA and Z-DNA. The figure shows levels of IgG antibodies to different DNA antigens in longitudinal sera from a patient with SLE. The DNA antigens were from calf thymus (CT), Micrococcus luteus (MC), Br-poly(dGdC) and unbrominated poly(dGdC). Br-poly(dGdC) represents Z-DNA. CT and MC DNA both represent B-DNA although MC DNA has Z-DNA content. Antibody levels were determined by an ELISA with results reported in terms of the OD450 values of the assay. Reproduced with permission from Spencer et al . 32 SLE, systemic lupus erythematosus.

Like SLE antibodies to B-DNA, antibodies to Z-DNA from patients depend on ionic interactions suggesting that the phosphodiester backbone is the main antigenic determinant. 32 33 Given the differences in the structure of the phosphodiester backbone in B-DNA and Z-DNA (smooth vs zig-zag, right-handed vs left-handed), cross-reactive binding is perhaps surprising. Cross-reactivity can extend to other charged antigens such as phospholipids, however, suggesting epitope spreading. 33 The presence of a broad array of anti-DNA specificities in SLE supports this mechanism in the setting of autoimmunity. 34

Unlike the antibodies to B-DNA which are specific for SLE, antibodies to Z-DNA can occur in other inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and drug-induced lupus; in these conditions, antibodies to B-DNA are not present. 31 35 36 Importantly, some studies have detected antibodies to Z-DNA in otherwise healthy humans (NHS). 32 33 Together, these findings suggest that antibodies in SLE that bind to both Z-DNA and B-DNA are indicative of a more generalised breakdown of immune tolerance. The predominance of ionic interactions in the binding of both B-DNA and Z-DNA by SLE anti-DNA could suggest a relatively ‘non-specific’ interaction based on charge; nevertheless, specificity is possible since the anti-Z-DNA antibodies in clinical settings other than SLE do not bind to B-DNA.

In their pattern of expression and binding interactions, antibodies to Z-DNA resemble antibodies that are specific for certain bacterial DNA and viral DNA antigens. 37–39 These antibodies occur in NHS as well as in patients with SLE, lack reactivity to B-DNA and are primarily the IgG2 isotype; in contrast, anti-B-DNA antibodies from patients with SLE primarily display IgG1, an isotype characteristic of T cell dependent responses. 37 Because of the specificity of these antibodies for sites on DNA from only certain bacteria or viruses, these antibodies are not detected in the standard assays used to screen for anti-DNA in patients.

The role of extracellular bacterial DNA in immunity

Recent research on biofilms has dramatically revealed the chameleon-like nature of DNA in the extracellular space and provides intriguing clues about the potential origin of anti-Z-DNA antibodies in both normal and aberrant immunity. 40–42 Biofilms represent communities of bacteria that are embedded in a multicomponent matrix to facilitate bacterial growth; biofilms provide nutritional support and protection from environmental influences, including antibiotics. Encounters with biofilms are almost inevitable in life since about 80% of infections involve biofilm formation; furthermore, bacteria in the microbiome grow as biofilms. Among components in the matrix, high molecular weight DNA can create extended arrays through its interaction with other macromolecules. The DNA present in biofilms can also promote immune responses through the activation of TLR9 (Toll-like receptor 9) by the unmethylated CpG motifs common in bacterial genomes. 43

In a fascinating study on biofilm structure, Buzzo et al showed that DNA in a biofilm can undergo a B-DNA to Z-DNA transition that may explain the protective effects of the biofilm. 44 This transition can result from the interaction of DNA with HU (histone-like protein) and IHF (integration host factor), two bacterial DNABII proteins incorporating HMG boxes that promote the B-DNA to Z-DNA transition. Both proteins bend DNA and most likely promote Z-DNA formation by stabilising BZj 45 ; this stabilisation overcomes the major energetic barrier to Z-DNA formation.

The data of Buzzo et al also suggest that biofilms formed by various organisms all express Z-DNA; the base composition of each genome, however, could perhaps affect the rate at which B-DNA flips to Z-DNA. Over time, Z-DNA will accumulate in biofilms since the left-handed DNA, unlike B-DNA, is resistant to digestion by mammalian DNases. 22 Indeed, a seminal study of Whitchurch et al 46 showed that DNase 1 can inhibit biofilms in vitro during their early stage of formation but cannot degrade mature films. Of note is the susceptibility of Z-DNA in biofilms to the S1 bacterial nuclease, contrasting with the resistance to mammalian DNases. 22 47 Importantly, Buzzo et al were able to promote the formation of biofilms in vitro by using a monoclonal antibody to bind and stabilise DNA in the Z-DNA conformation; a similar effect occurs with bacterial HU and HIS proteins. 44 In contrast to the anti-Z-DNA antibodies in SLE and NHS, the binding of the anti-Z-DNA monoclonal antibody in these experiments does not involve electrostatic interactions. 32

In addition to DNA of prokaryotic origin, eukaryotic DNA from neutrophils undergoing NETosis can also contribute to the biofilm structure. As neutrophils undergo NETosis, they release DNA which interacts with neutrophil granule proteins to form NETs or neutrophil extracellular traps. 48 NETs have anti-bacterial action and can ensnare and kill bacteria ( figure 3A ). Like DNA from the bacteria in the biofilm, DNA from NETs can undergo a B-DNA to Z-DNA transition under the influence of DNABII proteins. DNA in NETs may also undergo Z-DNA formation because host proteins such as HMGB1 can bend DNA to potentially stabilise BZj ( figure 3B ). Interestingly, the association of HMGB1 with DNA is increased by neutrophil elastase that removes the C-terminal acidic tail. 49

NETs, Z-DNA and pathways. (A) Extrusion of DNA from neutrophils along with other nuclear molecules leads to the formation of NETs and can be recognised by anti-B-DNA and anti-Z-DNA antibodies. The various proteases, anti-microbial proteins (AMP) and enzymes contribute to the antibacterial activity. Complement can opsonize bacterial DNA to promote clearance. (B) HMG box containing proteins like HU and IHF from bacteria and HMGB1 from the host promote the formation of B-DNA/Z-DNA junctions (BZj) that stabilise Z-DNA formation by NETs. (C) Different signalling pathways that regulate the proliferation of autoimmune B cells and interferon responses during inflammation. DNA can be delivered inside of cells following uptake by anti-DNA antibodies by the B cell receptor to deliver DNA into endosomes or through other pathways that deliver DNA to the cytoplasm. Once inside cells, DNA can interact with internal sensors and lead to signal transduction. These pathways complement those delivering DNA through Fc receptors (FcR) as immune complexes and through toll-like receptors to promote B cell proliferation and interferon responses. Intracellular activation of the Z-DNA binding protein 1 (ZBP1) sensor by Z-DNA or Z-RNA can activate RIPK3 (receptor interacting serine threonine kinase) to phosphorylate MLKL (mixed lineage domain like pseudokinase) to induce pore formation that results in necroptosis, a form of inflammatory cell death, and activation of inflammasomes. GSDM is gasdermin which can create pores to release the cytokines IL-1β and IL-18 or promote apoptosis. FAS and TLR signalling systems can have roles in B cell activation and apoptosis.

The immunogenicity of biofilm components has already received experimental support. Anti-DNA can be induced by immunisation with a complex of DNA and curli, an amyloid-forming protein found in biofilms. 50 51 Sera of patients with SLE or otherwise healthy individuals have antibodies to DNA-curli, consistent with exposure to biofilm. 52 In another setting, experimental infection of mice with Salmonella Typhimurium can induce anti-DNA autoantibody production. 53 Together, these findings suggest that infection can provide a source of Z-DNA to drive antibody responses that have tell-tale serological evidence of encounters with immunogenic bacterial DNA.

While the biochemical basis of the transition to Z-DNA still requires further investigation, the results are very important for thinking about lupus. Thus, Z-DNA resists nuclease digestion by enzymes such as DNase 1 and, thus far, a mammalian enzyme specific for Z-DNA has not been described. Once Z-DNA forms in the biofilm, it can provide a persistent and high concentration of antigen to induce antibody production; in this sense, the biofilm can act as a depot to supply antigen to the system. The persistence of a local source of Z-DNA in the tissue contrasts with the fate of B-DNA in the blood which is rapidly degraded within minutes. 54

Another finding that highlights the possible immunogenic role of Z-DNA relates to the propensity of bacterial genomic DNA to display Z-DNA. The GC content of bacterial DNA varies widely, with content as low as 20% and as high as 80%. 55 As shown recently, a monoclonal anti-Z-DNA antibody from a mouse and polyclonal anti-Z-DNA preparations can bind at high titers to DNA from Micrococcus luteus (MC) and Mycobacterium tuberculosis (MTb) under the ordinary conditions of an ELISA. 56 The GC content of MC DNA is 73%–74% and 65%–66% for MTb DNA compared with 40%–41% for human genomic and 44%–45% for mitochondrial DNA. 57–59 In these experiments, the anti-Z-DNA antibodies showed limited if any binding to other sources of DNA such as calf thymus DNA; in contrast, a monoclonal anti-Z-DNA bound Escherichia coli DNA (50%–51% GC). 56

Since biofilms represent arrays of Z-DNA antigen, these structures could act as thymus-independent antigens, with the activation of naïve B cells driven by multiple low-affinity interactions with a Z-DNA array. Consistent with this idea, antibodies to bacterial DNA in NHS are predominantly of the IgG2 isotype, rather than the IgG1 or IgG3 that are typical of T cell dependent responses. 37

The role of nucleases

Despite its origin in the cell nucleus, DNA occurs prominently in the extracellular space as a result of cell death and NETosis. 48 While much of the DNA initially generated from these processes is high molecular weight, DNA in the circulation is generally of much lower molecular mass, with a mean size of 166 bases pairs. 60 61 The marked reduction in size results from degradation by intracellular nucleases during phagocytosis of dead and dying cells as well as by extracellular nucleases in the tissue or blood. 62 The two main extracellular DNase enzymes are DNase 1 and DNase 1 like 3 (DNase 1L3). 63 While these enzymes have structural similarity, DNase 1 prefers free or naked DNA as the substrate while DNase 1L3 targets nucleosomal DNA. DNase 1 and DNase 1L3 both play a role in clearing and degrading DNA in the extracellular space, with deficiencies of these enzymes associated with diseases with features of SLE in both humans and mice. 64–66 While enzyme deficiencies can be genetic in origin, autoantibodies expressed by patients can inhibit enzyme activities to increase levels of extracellular DNA. 67

The role of DNases in degrading exogenous DNA in host defence is important. As shown by Lacey et al , deficiency of DNase 1 and DNase 1L3 increases the formation of biofilms during experimental infection of mice, consistent with prior studies showing the prevention of biofilm formation by DNase I in vitro. 68 These results suggest that DNase 1 and DNase 1L3, in addition to targeting DNA from dead and dying cells, can target non-self-DNA, whether arising from infection, colonisation or the microbiome. With enzyme deficiency, persistence of the biofilm would favour Z-DNA formation, increasing the amount of Z-DNA incorporated.

While Z-DNA is not susceptible to nuclease digestion by DNase 1 or DNase 1L3, proteolytic digestion of proteins such as HU, IHF and HMGB1 that stabilise Z-DNA could allow the flip back to B-DNA; this digestion could occur intra-cellularly or extra-cellularly, where enzymes like DNase 1 and DNase 1L3 can mediate NET destruction. In this clearance process, the classical pathway of complement may also play a role since C1q deficiency is one cause of monogenic lupus. 69 70 In other cases, antibodies binding to NETs may functionally produce C1q deficiency. 71 If unresolved, the NETs stabilised by anti-Z-DNA antibodies may be long-lived because of Z-DNA’s resistance to DNase, forming a positive feedback loop for inflammation.

Interestingly, current therapy may impact on these processes. An antimalarial agent such as hydroxychloroquine can shift the conformational equilibrium of DNA to favour B-DNA and could retard the development of biofilms. 72 In another action, hydroxychloroquine can increase the sensitivity of B-DNA to DNase digestion 73 and thereby reduce the formation of immunostimulatory Z-DNA in the biofilm, whether of bacterial or host origin. Finally, hydroxychloroquine can inhibit PAD4 (peptidyl arginine deiminase 4) in vitro to prevent the release of DNA from neutrophils during NETosis. 74

The role of nucleic acid sensors

Incorporating bacterial Z-DNA model into a model for lupus thus requires consideration of the intricacies of sensing of the Z conformation although most of the studies on this issue have focused on the recognition of RNA from viral infection or transcription of host retroelements. Figure 3C presents an overall schema for the sensing of Z nucleic acids and the many interactions and downstream consequences. Since the issue of Z-nucleic acid sensing is beyond the scope of this article, the reader is referred to reviews which describe sensing to Z nucleic acids. 75–78

Key to signalling by Z-nucleic acids 75 79 80 are two proteins: ZBP1 (Z binding protein 1) and ADAR1 (adenosine deaminase acting on RNA 1). ZBP1 was originally discovered as a cytoplasmic DNA sensor called DAI (DNA-dependent activator of IFN-regulatory factors) with subsequent studies demonstrating Z-nucleic acids as the ligand. 81 The other player in this system is ADAR1 (adenosine deaminase of RNA 1). ADAR1 has two major isoforms, p110 and p150, which catalyse the conversion of adenosine to inosine in double stranded RNA; this process is known as RNA editing. Both ADAR1 isoforms can sequester right-handed dsRNA molecules through three dsRNA binding domains; sequestration prevents the activation of other RNA sensing systems such as myeloma differentiation-associated gene 5 (MDA5) and Protein Kinase RNA specific (PKR) to limit immune responses.

ADAR1 p150 is the only isoform that can recognise Z-DNA and, like ZBP1, it can interact with Z-RNA through a Zα domain; this domain is lacking in ADAR1 p110, accounting for the difference in action. In this pathway, ADAR1 can bind to Z-RNA through its Zα domain to prevent activation of ZBP1. Interestingly, loss of function Zα domain variants of ADAR1 can produce Aicardi-Goutières syndrome, a type I interferonopathy that has some features of SLE. 82 Under normal cellular conditions, Z-RNA binding by ADAR1 prevents immune responses induced by self-transcripts from retroelements that have embedded Z-forming elements. 76

Interferon can induce the expression of both ADAR1 p150 and ZBP1, with differing consequences. Whereas ADAR1 can act as a negative regulator of the interferon response, ZBP1 can produce inflammatory cell death. 83 ( figure 3C ). Furthermore, with activation, ZBP1 can interact with RIPK3 to cause phosphorylation of MLKL (mixed lineage domain like protein); phosphorylated MLKL can self-assemble to form membrane pores, regardless of whether ZBP1 is triggered by Z-DNA or Z-RNA. These pores allow the release of DNA from various cell compartments, with DNA from mitochondria combining with ZBP1 to activate STING to induce interferon production. 84 Induction of high levels of Z-RNA from retroelements, which can occur during viral infections can amplify activation. 77 NLRP3 inflammasome activation to produce IL-1 and IL-18 can also occur with the flux of ions through the MLKL pores. 85–87 The role Z nucleic acids play in host defence may be reflected in the complex evolution of ZBP1 and ADAR1, with viruses such as smallpox and measles driving the selection of these molecules. 88 89

As these considerations suggest, sensing of Z nucleic acids can impact other systems (eg, STING, NLRP3 inflammasome) that can exert adjuvant activity for induction of antibodies to Z-DNA. In this regard, DNA from bacteria may trigger TLR9 (via CpG motifs), cGAS-STING (presence in the cytoplasm) and ZBP1 (either through Z-forming sequences in the genome or conformational changes in the biofilm). Thus, even though sensing of Z nucleic acids frequently involves RNA, this system could significantly boost antibody responses to DNA in health and autoimmunity.

DNA as a chameleon

To highlight a novel mechanism of host defence, we would like to apply the term chameleon to bacterial and host DNA as it transitions from B-DNA to Z-DNA in the setting of the biofilm. The term also applies to DNA from NETs which, under the influence of DNA binding proteins with an HMG domain, can form Z-DNA. These binding proteins may stabilise BZj by bending DNA to a lower the energy barrier to flip from B-DNA to Z-DNA. The formation of Z-DNA may also be promoted by the presence of oxidised bases, such as 8-oxodG (8-oxo-2′-deoxguanosine), through the release of NADPH oxidase during NETosis and by H 2 O 2 production catalysed by DNA. 90–92 Furthermore, adjuvant effects could result from interferon-induced expression of Z-RNA, internalisation of antibody-bound Z-DNA or the occurrence of cell death triggered by ZBP1.

The serological studies on anti-Z-DNA in humans suggest that, in normal individuals, induced antibodies obey the rules and are specific for the Z-DNA structure. In SLE, antibody cross-reactivity between B-DNA and Z-DNA may occur because of the disturbances in the B cell repertoire. In addition, disturbances in developmental checkpoints may allow retention of precursors that are polyreactive and bind broadly to DNA. 93 94 In the setting of a biofilm where Z-DNA concentrations are high, T cell independent activation of autoreactive B cells may occur, accounting for the expression of antibodies to nuclear molecules (including those from NETs) in individuals genetically prone to autoimmunity. 95 96

This model does not necessitate a role of self DNA in the induction of the anti-DNA response since foreign DNA (ie, bacterial or viral) has regions of both B-DNA and Z-DNA depending on the infecting organism, the stage of the biofilm or the sequence of the DNA. While not excluding a role of self or B-DNA in inducing anti-DNA autoantibody production, a model of anti-DNA based on the changing immunological properties of DNA focuses attention on the potential roles of infection, NETosis and stress in pathogenesis; this model also incorporates the role of host DNase enzymes which, while effective in clearing B-DNA, may be stymied by a Z-DNA.

Every analogy has its limitations but the term chameleon appears apt to describe the structural transformations that DNA can undergo. For lizards, the colour change is defensive and protective, and hides the lizard from predators. In a related way, the transition from B-DNA to Z-DNA may protect the bacteria from elements of the immune system. Future studies will explore approaches to block the B-DNA to Z-DNA transition and determine the impact of anti-DNA antibodies on the course of lupus as well as the role of any ongoing infections or microbiome blooms provoking disease flares. Finally, new approaches to treating biofilms may also change the colour of the immune system in both autoimmune and infectious disease.

Ethics statements

Patient consent for publication.

Not applicable.

Ethics approval

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Handling editor Josef S Smolen

Contributors DSP and AH wrote the article together.

Funding Work completed in DSP’s lab was supported by a Veterans Administration Merit Review grant (BX003772) and a National Institutes of Health grant (R01AR073935).

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

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Early iterations of the AI applications we interact with most today were built on traditional machine learning models. These models rely on learning algorithms that are developed and maintained by data scientists. In other words, traditional machine learning models need human intervention to process new information and perform any new task that falls outside their initial training.

For example, Apple made Siri a feature of its iOS in 2011. This early version of Siri was trained to understand a set of highly specific statements and requests. Human intervention was required to expand Siri’s knowledge base and functionality.

However, AI capabilities have been evolving steadily since the breakthrough development of  artificial neural networks  in 2012, which allow machines to engage in reinforcement learning and simulate how the human brain processes information.

Unlike basic machine learning models, deep learning models allow AI applications to learn how to perform new tasks that need human intelligence, engage in new behaviors and make decisions without human intervention. As a result, deep learning has enabled task automation, content generation, predictive maintenance and other capabilities across  industries .

Due to deep learning and other advancements, the field of AI remains in a constant and fast-paced state of flux. Our collective understanding of realized AI and theoretical AI continues to shift, meaning AI categories and AI terminology may differ (and overlap) from one source to the next. However, the types of AI can be largely understood by examining two encompassing categories: AI capabilities and AI functionalities.

1. Artificial Narrow AI

Artificial Narrow Intelligence, also known as Weak AI (what we refer to as Narrow AI), is the only type of AI that exists today. Any other form of AI is theoretical. It can be trained to perform a single or narrow task, often far faster and better than a human mind can.

However, it can’t perform outside of its defined task. Instead, it targets a single subset of cognitive abilities and advances in that spectrum. Siri, Amazon’s Alexa and IBM Watson are examples of Narrow AI. Even OpenAI’s ChatGPT is considered a form of Narrow AI because it’s limited to the single task of text-based chat.

2. General AI

Artificial General Intelligence (AGI), also known as  Strong AI , is today nothing more than a theoretical concept. AGI can use previous learnings and skills to accomplish new tasks in a different context without the need for human beings to train the underlying models. This ability allows AGI to learn and perform any intellectual task that a human being can.

3. Super AI

Super AI is commonly referred to as artificial superintelligence and, like AGI, is strictly theoretical. If ever realized, Super AI would think, reason, learn, make judgements and possess cognitive abilities that surpass those of human beings.

The applications possessing Super AI capabilities will have evolved beyond the point of understanding human sentiments and experiences to feel emotions, have needs and possess beliefs and desires of their own.

Underneath Narrow AI, one of the three types based on capabilities, there are two functional AI categories:

1. Reactive Machine AI

Reactive machines are AI systems with no memory and are designed to perform a very specific task. Since they can’t recollect previous outcomes or decisions, they only work with presently available data. Reactive AI stems from statistical math and can analyze vast amounts of data to produce a seemingly intelligent output.

Examples of Reactive Machine AI  

• IBM Deep Blue: IBM’s chess-playing supercomputer AI beat chess grandmaster Garry Kasparov in the late 1990s by analyzing the pieces on the board and predicting the probable outcomes of each move.
• The Netflix Recommendation Engine: Netflix’s viewing recommendations are powered by models that process data sets collected from viewing history to provide customers with content they’re most likely to enjoy.

2. Limited Memory AI

Unlike Reactive Machine AI, this form of AI can recall past events and outcomes and monitor specific objects or situations over time. Limited Memory AI can use past- and present-moment data to decide on a course of action most likely to help achieve a desired outcome.

However, while Limited Memory AI can use past data for a specific amount of time, it can’t retain that data in a library of past experiences to use over a long-term period. As it’s trained on more data over time, Limited Memory AI can improve in performance.

Examples of Limited Memory AI  

• Generative AI: Generative AI tools such as ChatGPT, Bard and DeepAI rely on limited memory AI capabilities to predict the next word, phrase or visual element within the content it’s generating.
• Virtual assistants and chatbots: Siri, Alexa, Google Assistant, Cortana and IBM Watson Assistant combine natural language processing (NLP) and Limited Memory AI to understand questions and requests, take appropriate actions and compose responses.
• Self-driving cars: Autonomous vehicles use Limited Memory AI to understand the world around them in real-time and make informed decisions on when to apply speed, brake, make a turn, etc.

3. Theory of Mind AI

Theory of Mind AI is a functional class of AI that falls underneath the General AI. Though an unrealized form of AI today, AI with Theory of Mind functionality would understand the thoughts and emotions of other entities. This understanding can affect how the AI interacts with those around them. In theory, this would allow the AI to simulate human-like relationships.

Because Theory of Mind AI could infer human motives and reasoning, it would personalize its interactions with individuals based on their unique emotional needs and intentions. Theory of Mind AI would also be able to understand and contextualize artwork and essays, which today’s generative AI tools are unable to do.

Emotion AI is a theory of mind AI currently in development. AI researchers hope it will have the ability to analyze voices, images and other kinds of data to recognize, simulate, monitor and respond appropriately to humans on an emotional level. To date, Emotion AI is unable to understand and respond to human feelings.  

4. Self-Aware AI

Self-Aware AI is a kind of functional AI class for applications that would possess super AI capabilities. Like theory of mind AI, Self-Aware AI is strictly theoretical. If ever achieved, it would have the ability to understand its own internal conditions and traits along with human emotions and thoughts. It would also have its own set of emotions, needs and beliefs.

Emotion AI is a Theory of Mind AI currently in development. Researchers hope it will have the ability to analyze voices, images and other kinds of data to recognize, simulate, monitor and respond appropriately to humans on an emotional level. To date, Emotion AI is unable to understand and respond to human feelings.

Computer vision

Narrow AI applications with  computer vision  can be trained to interpret and analyze the visual world. This allows intelligent machines to identify and classify objects within images and video footage.

Applications of computer vision include:

• Image recognition and classification
• Object detection
• Object tracking
• Facial recognition
• Content-based image retrieval

Computer vision is critical for use cases that involve AI machines interacting and traversing the physical world around them. Examples include self-driving cars and machines navigating warehouses and other environments.

Robots in industrial settings can use Narrow AI to perform routine, repetitive tasks that involve materials handling, assembly and quality inspections. In healthcare, robots equipped with Narrow AI can assist surgeons in monitoring vitals and detecting potential issues during procedures.

Agricultural machines can engage in autonomous pruning, moving, thinning, seeding and spraying. And smart home devices such as the iRobot Roomba can navigate a home’s interior using computer vision and use data stored in memory to understand its progress.

Expert systems

Expert systems equipped with Narrow AI capabilities can be trained on a corpus to emulate the human decision-making process and apply expertise to solve complex problems. These systems can evaluate vast amounts of data to uncover trends and patterns to make decisions. They can also help businesses predict future events and understand why past events occurred.

IBM has pioneered AI from the very beginning, contributing breakthrough after breakthrough to the field. IBM most recently released a big upgrade to its cloud-based, generative AI platform known as watsonx.  IBM watsonx.ai  brings together new generative AI capabilities, powered by foundation models and traditional machine learning into a powerful studio spanning the entire AI lifecycle. With watsonx.ai, data scientists can build, train and deploy machine learning models in a single collaborative studio environment.

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