ABOUT THE STUDY

JOURNAL: Nature Communications

TITLE: “Photooxidation Driven Formation of Fe-Au Linked Ferrocene-Based Single-Molecule Junctions”

AUTHORS: Woojung Lee (1), Liang Li (1), Maria Camarasa-Gomez (2), Daniel Hernangomez-Perez (2) , Xavier Roy (1), Ferdinand Evers (2*) Michael S. Inkpen (3*), Latha Venkataraman (1,4*)

1. Department of Chemistry, Columbia University
2. Institute of Theoretical Physics, University of Regensburg, Germany
3. Department of Chemistry, University of Southern California, Los Angeles
4. Department of Applied Physics and Applied Mathematics, Columbia Engineering

FUNDING: This work was supported in part by the National Science Foundation MRSEC grant on Precision-Assembled Quantum Materials (DMR-2011738) and the National Science Foundation under grant DMR-2241180. M.S.I. was supported by a Marie Sklodowska Curie Global Fellowship (MOLCLICK: 657247) within the Horizon 2020 Programme and University of Southern California (USC) startup funds. We thank the NSF (DBI-0821671, CHE-0840366, CHE-1048807) and the NIH (S10 RR25432) for USC-based analytical instrumentation. M.C.-G., D.H.-P., and F.E. acknowledge financial support from the German Research Foundation (DFG) through Research Training Group (GRK) 1570 and Collaborative Research Center (SFB) 1277 - Project ID 314695032 (subprojects A03, B01). We thank Brandon Fowler and Nils Rotthowe for help with Mass-Spectroscopy, Giacomo Lovat for help with STM-BJ data acquisition, and Rachel Austin for discussions.

COI: The authors declare no competing financial or non-financial interests.

Traumatic stress can have devastating effects on people, in particular those in the military, including mental illness, substance abuse, post-traumatic stress disorder, family violence, and suicide. Developing effective approaches to prevent suicide and improve treatments is a top priority within the U.S. Department of Defense (DOD).

New DARPA program

A new program from DARPA (Defense Advanced Research Projects Agency), the DOD’s central research and development organization, has awarded $12 million to a multi-institutional team led by Paul Sajda, department chair and Vikram S. Pandit Professor of Biomedical Engineering at Columbia Engineering, to advance critical research in major depressive disorder (MDD) and suicide. 

An interdisciplinary team

Sajda will be working with an interdisciplinary group that includes engineers, neuroscientists, and clinicians at the Medical University of South Carolina (MUSC), the University of Wisconsin-Madison, and the University of Oklahoma. The team is a close-knit one -- many of them have been working together for more than 10 years, including collaborating on clinical trials that link precision neurostimulation therapy to clinical outcomes.

The grant is one of three research projects funded by DARPA’s STRENGTHEN program, Strengthening Resilient Emotions and Nimble Cognition Through Engineering Neuroplasticity, which aims to build on recent advances in neuroscience and clinical practice to increase well-being and prevent or mitigate the effects of traumatic stress leading to behavioral health disorders and suicidality.

Brain stimulation techniques for treatment-resistant depression

The researchers are building on NIH-funded work aimed at developing brain stimulation techniques to treat cases of treatment-resistant depression disorder. They recently completed a six-week-long clinical study that used repetitive transcranial magnetic stimulation (rTMS), triggered by electroencephalography (EEG), to synchronize brainwaves, to induce a brain state known as “entrainment.” The study demonstrated that patients with better entrainment had greater treatment improvement, spotlighting the strong potential for EEG-informed rTMS therapy in cases of resistant MDD.

A new generation of psychiatric treatment

“The psychiatric field needs new ways to tackle treatment-resistant major depressive disorder, which does not respond to existing drug therapy or psychotherapy,” says Sajda, who is also affiliated with Columbia’s Data Science Institute. “Our team has decades of experience using innovative brain stimulation methods and multi-modal imaging in psychiatry. We expect our revolutionary approach in delivering individualized internal and external interventions to entrain brain networks will result in neuroplastic changes that improve clinical outcomes.”

His lab has decades of experience using innovative brain stimulation methods and multi-modal imaging in psychiatry. The DARPA-funded project — Realigning Emotion and COgnition Via prEcision Regulation of networkS (RECOVER) — is focused on developing a new generation of psychiatric treatment to guide the brain’s neuroplasticity, its natural ability to form new neural connections. 

The clinical study will be run at MUSC, under the lead of co-PI Lisa McTeague, associate professor in the Brain Stimulation Division of the Department of Psychiatry and Behavioral Science at MUSC. Dr. McTeague is also a practicing clinical psychologist in the PTSD Clinical Team at the Ralph H. Johnson VA Health Care System. She and her group at MUSC have been working with Sajda for 10 years. 

Promoting brain’s cognitive flexibility and emotional regulation to overcome depression and process trauma

The team hopes to reduce clinical symptoms of depression, anxiety, and suicidality by promoting cognitive flexibility (CF) -- the mental ability to switch between thinking about two different concepts according to the context of a situation -- and emotional regulation (ER) -- a conscious or nonconscious strategy to start, stop, or otherwise modulate the trajectory of an emotion. Together, CF and ER are essential to overcoming depression and processing trauma.

The researchers posit CF and ER are strongly influenced by patterns of electrical activity in the brain, called alpha oscillations. They believe that tweaking alpha oscillations using transcranial magnetic stimulation can improve a patient’s cognitive flexibility and emotional regulation by encouraging neuroplasticity. When combined with interventions such as cognitive-behavioral therapy, this new approach has tremendous potential to transform mental health. 

Applying functional magnetic resonance imaging, electroencephalography, and transcranial magnetic stimulation

Their approach brings together a suite of familiar techniques that noninvasively image and manipulate the brain. By simultaneously using functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and transcranial magnetic stimulation (TMS), the researchers hope to develop an entirely new approach for treating this debilitating mental disorder. 

The team also hopes to translate their findings and build a less expensive and more widely available system based on simultaneous functional near-infrared spectroscopy (fNIRS), EEG, and TMS. This part of the project will be co-led by the Investigator Han Yuan, associate professor at the University of Oklahoma’s Stephenson School of Biomedical Engineering.

“The clinical trials we have completed, funded by NIH and done at MUSC, have shown to be very promising, and this new DARPA award will help us extend the approach even further, adding hybrid treatments as well as expanding our approach to addressing other forms of mental illness, such as PTSD and suicidality,” says Sajda. “We will build on recent advances in neuroscience and clinical practice to increase well-being and prevent or mitigate the effects of traumatic stress leading to behavioral health disorders and suicidality.”

About the Study

Journal: Science

Title: “Probiotic-guided CAR-T cells for solid tumor targeting”

Authors: Rosa L. Vincent(1), Candice R. Gurbatri(1), Fangda Li2, Ana Vardoshvili(1), Courtney Coker(1), Jongwon Im(1), Edward R. Ballister(1,2), Mathieu Rouanne(2), Thomas Savage(2), Kenia de los Santos-Alexis(2), Andrew Redenti(1,2), Leonie Brockmann(2), Meghna Komaranchath(1), Nicholas Arpaia(2,3), Tal Danino(1,3,4)

1. Department of Biomedical Engineering, Columbia Engineering
2. Department of Microbiology & Immunology, Vagelos College of Physicians and Surgeons of Columbia University
3. Herbert Irving Comprehensive Cancer Center, Columbia University
4. Data Science Institute, Columbia University

Funding: This work was supported by NIH 1R01EB030352, Columbia Translational Therapeutics (TRx) Award, and the NSF Graduate Research Fellowship (1644869 to C.R.G.).

COI: R.L.V., T.M.S., C.R.G., J.I., N.A., and T.D. are inventors on a patent application describing the use of Probiotic-guided CAR-T cells for cancer immunotherapy (International Application No. PCT/US2022/016775). 

Recent work directed by professors Ronghui Gu and Jason Nieh introduced a new tool, Spoq, that significantly reduces the complex efforts people must use to verify real-world software and makes it possible to verify existing C systems code without modifications. Formal verification offers a systematic and rigorous approach to software and hardware verification, helping to ensure that systems behave correctly and meet their intended specifications. With Spoq, many aspects of formal verification can be automated, significantly reducing manual proof efforts for verification. The paper was presented at the 17th USENIX Symposium on Operating Systems Design and Implementation (OSDI) Conference on July 12, 2023.

Why it matters

System software forms the software foundations of our computing infrastructure. Modern system software is large, complex, and imperfect, with vulnerabilities that can be exploited to compromise the security of a system. Formal verification offers a potential solution to this problem by mathematically proving that system software can provide critical security guarantees. Unfortunately, it remains too difficult and requires too much human effort to apply in practice.

Previous tools developed by Nieh’s and Gu’s teams introduced verification techniques to make certain proofs possible that could not have been done before. Spoq’s key feature is that it automates the tedious and time-consuming parts of many proofs. “Spoq can generate results in about an hour compared to doing it manually, which can take months or years to formally verify a system,” says Xupeng Li, the paper's lead author and a PhD student with both Nieh and Gu.

What's next

Over the next few months, the lab is focused on making Spoq open-source so that formal verification can be widely deployed to secure the foundations of our computing infrastructure's software.

About the Study

Conference: 17th USENIX Symposium on Operating Systems Design and Implementation (OSDI) Conference (July 10-12, 2023, Boston, MA)

Title: “Spoq: Scaling Machine-Checkable Systems Verification in Coq”

Authors: Xupeng Li, Xuheng Li, Wei Qiang, Ronghui Gu, and Jason Nieh, Columbia Engineering

Funding: This work was supported in part by three Amazon Research Awards, a Guggenheim Fellowship, a VMware Systems Research Award, an NSF CAREER Award, DARPA contract N66001-21-C-4018, and NSF grants CCF-1918400, CNS-2052947, and CCF-2124080. 

COI: Ronghui Gu is the founder of and has an equity interest in CertiK.

Header image: Tang Family Assistant Professor of Computer Science Rongui Gu (left) and Professor of Computer Science Jason Nieh (right).

Over time, the AI system, which the team designed by modifying a state-of-the-art framework, got better at telling when seemingly unique fingerprints belonged to the same person and when they didn’t. The accuracy for a single pair reached 77%. When multiple pairs were presented, the accuracy shot significantly higher, potentially increasing current forensic efficiency by more than tenfold. The project, a collaboration between Hod Lipson’s Creative Machines lab at Columbia Engineering and Wenyao Xu’s Embedded Sensors and Computing lab at University at Buffalo, SUNY, was published today in Science Advances.

Study findings challenge–and surprise–forensics community

Once the team verified their results, they quickly sent the findings to a well-established forensics journal, only to receive a rejection a few months later. The anonymous expert reviewer and editor concluded that “It is well known that every fingerprint is unique,” and therefore it would not be possible to detect similarities even if the fingerprints came from the same person. 

The team did not give up. They doubled down on the lead, fed their AI system even more data, and the system kept improving. Aware of the forensics community's skepticism, the team opted to submit their manuscript to a more general audience. The paper was rejected again, but Lipson, who is the James and Sally Scapa Professor of Innovation in the Department of Mechanical Engineering and co-director of the Makerspace Facility, appealed. “I don’t normally argue editorial decisions, but this finding was too important to ignore,” he said. “If this information tips the balance, then I imagine that cold cases could be revived, and even that innocent people could be acquitted.” 

While the system’s accuracy is not sufficient to officially decide a case, it can help prioritize leads in ambiguous situations. After more back and forth, the paper was finally accepted for publication by Science Advances.

Unveiled: a new kind of forensic marker to precisely capture fingerprints

One of the sticking points was the following question: What alternative information was the AI actually using that has evaded decades of forensic analysis? After careful visualizations of the AI system’s decision process, the team concluded that the AI was using a new kind of forensic marker. 

“The AI was not using ‘minutiae,’ which are the branchings and endpoints in fingerprint ridges – the patterns used in traditional fingerprint comparison,” said Guo, who began the study as a first-year student at Columbia Engineering in 2021. “Instead, it was using something else, related to the angles and curvatures of the swirls and loops in the center of the fingerprint.” 

Columbia Engineering senior Aniv Ray and PhD student Judah Goldfeder, who helped analyze the data, noted that their results are just the beginning. “Just imagine how well this will perform once it’s trained on millions, instead of thousands of fingerprints,” said Ray.

A need for broader datasets

The team is aware of potential biases in the data. The authors present evidence that indicates that the AI performs similarly across genders and races, where samples were available. However, they note, more careful validation needs to be done using datasets with broader coverage if this technique is to be used in practice.

Transformative potential of AI in a well-established field

This discovery is an example of more surprising things to come from AI, notes Lipson. “Many people think that AI cannot really make new discoveries–that it just regurgitates knowledge,” he said. “But this research is an example of how even a fairly simple AI, given a fairly plain dataset that the research community has had lying around for years, can provide insights that have eluded experts for decades.” 

He added, “Even more exciting is the fact that an undergraduate student, with no background in forensics whatsoever, can use AI to successfully challenge a widely held belief of an entire field. We are about to experience an explosion of AI-led scientific discovery by non-experts, and the expert community, including academia, needs to get ready.”

About the Study

Journal: Science Advances

Title: Unveiling Intra-Person Fingerprint Similarity via Deep Contrastive Learning

Authors: Gabe Guo, Aniv Ray, Judah Goldfeder, and Hod Lipson, Columbia Engineering; Miles Izydorczak, Tufts University; and Wenyao Xu, University at Buffalo, SUNY.

The work is part of a joint University of Washington, Columbia, and Harvard NSF AI Institute for Dynamical Systems, aimed to accelerate scientific discovery using AI.

Funding: The study was supported by NSF AI Institute for Dynamical Systems 2112085, and NSF REU Site 2050910.

COI: The authors declare no financial or other conflicts of interest.

Blockchains and the applications they support raise new challenges for economics, computer science, and game theory.

At the 2023 Columbia CryptoEconomics (CCE) Workshop, held December 6-7, practitioners, researchers, and academics gathered at the University’s Manhattanville campus to discuss challenges, recent progress, and opportunities in the economics of blockchain protocols. In keynote presentations, contributed talks, and panel discussions, leading experts discussed topics including proposer-builder separation, MEV, layer 1 security rehypothecation/restaking, and roll-ups.

The workshop, which was co-hosted by the Briger Family Digital Finance Lab at Columbia Business School, Columbia Engineering, and the Ethereum Foundation, underscored Columbia’s commitment to interdisciplinary research that seeks impact beyond the walls of the University. 

“We advocate for the convergent collaboration among academics, practitioners, and industry,” said Shih-Fu Chang, dean of Columbia Engineering and Morris A. and Alma Schapiro Professor of Engineering, in his opening remarks. 

“As interest in the crypto space waxes and wanes, support at various universities has come and gone,” said co-organizer Tim Roughgarden, professor of computer science at Columbia Engineering and the head of research at a16z Crypto. “Columbia has been fairly unique among its peer institutions by having unflagging support for the advancement of this technology and the science behind it.”

Details about the event and a full lineup are available here.

Full recordings of all sessions are available here.