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"Funk, Jonathan"
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ProteusAI: An Open-Source and User-Friendly Platform for Machine Learning-Guided Protein Design and Engineering
2024
Protein design and engineering are crucial for advancements in biotechnology, medicine, and sustainability. Machine learning (ML) models are used to design or enhance protein properties such as stability, catalytic activity, and selectivity. However, many existing ML tools require specialized expertise or lack open-source availability, limiting broader use and further development. To address this, we developed ProteusAI, a user-friendly and open-source ML platform to streamline protein engineering and design tasks. ProteusAI offers modules to support researchers in various stages of the design-build-test-learn (DBTL) cycle, including protein discovery, structure-based design, zero-shot predictions, and ML-guided directed evolution (MLDE). Our benchmarking results demonstrate ProteusAI’s efficiency in improving proteins and enyzmes within a few DBTL-cycle iterations. ProteusAI democratizes access to ML-guided protein engineering and is freely available for academic and commercial use. Future work aims to expand and integrate novel methods in computational protein and enzyme design to further develop ProteusAI.
Salvation through Participation: Developing a Polanyian-informed, Inclusivistic Soteriology
by
Funk, Jonathan
in
Bacon, Francis (1561-1626)
,
Biblical studies
,
Justin (Justin Martyr) (100?-165?)
2012
This paper wrestles with the mystery of how God's gift of salvation is extended to and received by humankind. In so doing, the paper affirms an inclusivistic theology of religions, to include an appreciation for mission as God's mission (i.e., missio Dei), as championed by scholars such as Clark Pinnock. Upon this foundation, the paper seeks to further the discussion through formulation of a pneumatological epistemology—one that looks to Michael Polanyi's theory of tacit knowledge to provide a context for better understanding the Spirit / human relationship as addressed throughout Scripture, particularly in the Paraclete passages of John as well as select Pauline epistles. Ultimately, this paper argues that saving knowledge is Spirit-breathed and, as such, is not constrained by human evangelistic activity but rather is afforded to all of humankind in a highly personalized way within the context of each person's life experience.
Dissertation
De novo Design of All-atom Biomolecular Interactions with RFdiffusion3
2025
Deep learning has accelerated protein design, but most existing methods are restricted to generating protein backbone coordinates and often neglect interactions with other biomolecules. We present RFdiffusion3 (RFD3), a diffusion model that generates protein structures in the context of ligands, nucleic acids and other non-protein constellations of atoms. Because all polymer atoms are modeled explicitly, conditioning the model on complex sets of atom-level constraints for enzyme design and other challenges is both simpler and more effective than previous approaches. RFD3 achieves improved performance compared to prior approaches on a range of
benchmarks with one tenth the computational cost. Finally, we demonstrate the broad applicability of RFD3 by designing and experimentally characterizing DNA binding proteins and cysteine hydrolases. The ability to rapidly generate protein structures guided by complex sets of atom-level constraints in the context of arbitrary non-protein atoms should further expand the range of functions attainable through protein design.
Journal Article
Accelerating Biomolecular Modeling with AtomWorks and RF3
2025
Deep learning methods trained on protein structure databases have revolutionized biomolecular structure prediction, but developing and training new models remains a considerable challenge. To facilitate the development of new models, we present AtomWorks: a broadly applicable data framework for developing state-of-the-art biomolecular foundation models spanning diverse tasks, including structure prediction, generative protein design, and fixed backbone sequence design. We use AtomWorks to train RosettaFold-3 (RF3), a structure prediction network capable of predicting arbitrary biomolecular complexes with an improved treatment of chirality that narrows the performance gap between closed-source AlphaFold3 (AF3) and existing open-source implementations. We expect that AtomWorks will accelerate the next generation of open-source biomolecular machine learning models and that RF3 will be broadly useful as a structure prediction tool. To this end, we release the AtomWorks framework (https://github.com/RosettaCommons/atomworks), together with curated training data, code and model weights for RF3 (https://github.com/RosettaCommons/modelforge) under a permissive BSD license.
Journal Article
RECENT RULINGS ON REORGANIZATIONS AND REITS
2015
The rapid changes in the global economy throughout recent years have challenged corporations to remain competitive. One approach to doing so has been reorganization or restructuring. There are several reasons for reorganizing a corporation, but the underlying drivers tend to be increasing profits and maximizing overall efficiency. C-suite executives often view reorganizations as a means to rectify problems that are being encountered by their corporation. Section 368, which governs tax-free reorganizations, is one of the more complex areas of the Code. One benefit of Section 368 is tax-free reorganization treatment for certain reorganizational structures that utilize one of the methods that it outlines. The past several years have seen real estate investment trusts (REIT) being formed as part of corporate reorganizations, and even entire corporate conversions to REIT status. The trend towards formation of and conversion to REITs is partially the result of favorable market conditions in real estate, including the low interest rate climate.
Trade Publication Article
PLEASE DISPOSE PROPERLY-TAX ISSUES AND POTENTIAL PITFALLS IN DISPOSING OF PRIVATE REITS
2015
Real estate investment trusts, or REITs, are entities devoted to owning or investing in various types of real estate as outlined in Sections 856-859 of the Code. REITs are generally taxable as corporations, but for the important distinction that they are permitted to deduct the dividends paid to their shareholders each year for federal income tax purposes. As a result of this dividends-paid deduction, REITs generally pay little to no federal income taxes; the income is instead taxed at the shareholder level as it is distributed to shareholders in the form of taxable dividends. REITs are required to meet many tests and restrictions regarding their organization, ownership, assets, income, and distributions in order to qualify and continue operating as REITs. Section 856(c)(4) contains the specific requirements of the REIT asset tests, including the requirement that at least 75% of the value of the REIT's total assets must be represented by real estate assets, cash and cash items, and government securities. Further, Section 856(c)(4) requires that all of the asset tests be met \"at the close of each quarter of the taxable year.\"
Trade Publication Article
RECENT REIT PROPOSALS FROM INSIDE THE BELTWAY
by
Funk, Jonathan L
,
Griffiths, D Brock
in
Built-in gains & losses
,
Carried interest
,
Corporate taxes
2014
Tax reform is a common topic of discussion in Washington these days. Trying to appease the voters, politicians are attempting to make the tax regime of the US more business-friendly while not reducing the amount of revenue collected by the Treasury. This article will focus on the proposals that would significantly impact REITs. Because most REITs tend to have partnership investments -- either through UPREIT (Umbrella Partnership REIT) or DownREIT structures, this article also will address many of the significant partnership tax proposals. Given the gridlock in Congress, it seems unlikely that the Obama administration proposals or the Camp proposal will receive enough bipartisan support to survive in their entirety. It is more likely that some of these proposals, or similar ideas, could resurface in future legislation. Consequently, although not surprisingly, REITs may encounter future legislative challenges.
Trade Publication Article
Anhydrite-bearing igneous breccias in the El Teniente copper deposit, Chile
by
Funk, Jonathan Andrew
in
Geology
2006
The El Teniente Cu deposit, located in the Andes of central Chile (34°S), is associated with a variety of late Miocene to early Pliocene hydrothermal breccias. Two types of anhydrite-bearing igneous breccias previously named by mine geologists as \"Andesite\" and \"Microdiorite\" Igneous Breccia (AIB and MIB, respectively) are located at the center of a hydrothermal breccia complex on the East side of the deposit. Both breccias include clasts of the rocks into which they intruded. However, the MIB surrounds an ∼100m wide, clast-free stock that is referred to as \"Porphyry A\", although it is not porphyritic. The MIB is temporally and genetically related to the hydrothermal anhydrite breccia that surrounds it. The AIB contains clasts of the MIB, and therefore intruded subsequent to the MIB. Major minerals in the MIB matrix are sodic plagioclase (An4-7), quartz, K-feldspar, poikilitic anhydrite (>30 modal %), Cu-sulfides, and biotite. The AIB matrix is a fine-grained, equigranular igneous rock that contains abundant biotite, sodic plagioclase (An25-32), quartz, interstitial anhydrite (<10 modal %) and Fe-oxides. Except near later hydrothermal veins, matrix minerals of both breccias exhibit planar crystal boundaries suggesting that they are primary phases that formed in the open space created by brecciation and not secondary alteration phases. Disparate crystallization temperatures obtained using Ti-in-biotite and S and O isotope geothermometers suggest various degrees of S and O isotopic disequilibrium. From textural, mineralogical, and chemical evidence, anhydrite in the AIB is a magmatic phase, while anhydrite in the MIB crystallized from an aqueous fluid/vapor exsolved from the same magma that formed the rest of the rock. Major and trace element chemistry of these rocks suggest that they were formed from highly evolved magmas enriched in S and Cu; however, Nd and Sr isotope data imply their derivation from the same long-lived, magmatic source as all the other igneous rocks in the deposit. Processes that may have contributed to the formation of the high fO2, Cu-, S-, and volatile-rich magmas that formed the AIB and MIB igneous breccias include igneous fractionation involving fluid/vapor-phase transport, magma mixing, and possible assimilation of the associated hydrothermal anhydrite breccia.
Dissertation
THE RARE AND REFRESHING REV. PROC. 2009-37
2010
At a recent luncheon with taxpayers, tax advisors, and Treasury Department officials, participants paused to provide sincere and enthusiastic applause for guidance provided by the treasury and the Service in the form of Rev. Proc. 2009-37. In the tax world, taxpayers and their advisors provide such a positive response to the Treasury and the Service about as frequently as Halley's comet passes by Earth -- and when it does happen, most people just do not see or appreciate it. Section 108(i), which was signed into law by Pres Obama on Feb 17, 2009, provides deferral relief to a variety of debt-laden businesses. Under Section 108(i), a taxpayer can elect to defer the recognition of cancellation of indebtedness (COD) income until 2014 on the reacquisition of an applicable debt instrument (ADI) in 2009 or 2010. Congress provided little direction on how pass-through entities should allocate the deferred COD income to their interest holders.
Trade Publication Article