We provide a family-wide assessment of accessible sites for covalent targeting that combined with AlphaFold revealed predicted small molecule binding pockets for guiding future inhibitor development of the DGK superfamily.
more » « less- Award ID(s):
- 2422750
- NSF-PAR ID:
- 10506256
- Publisher / Repository:
- the Royal Society of Chemistry
- Date Published:
- Journal Name:
- RSC Chemical Biology
- Volume:
- 4
- Issue:
- 6
- ISSN:
- 2633-0679
- Page Range / eLocation ID:
- 422 to 430
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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For domains in R d \mathbb {R}^d , d ≥ 2 d\geq 2 , we prove universal upper and lower bounds on the product of the bottom of the spectrum for the Laplacian to the power p > 0 p>0 and the supremum over all starting points of the p p -moments of the exit time of Brownian motion. It is shown that the lower bound is sharp for integer values of p p and that for p ≥ 1 p \geq 1 , the upper bound is asymptotically sharp as d → ∞ d\to \infty . For all p > 0 p>0 , we prove the existence of an extremal domain among the class of domains that are convex and symmetric with respect to all coordinate axes. For this class of domains we conjecture that the cube is extremal.more » « less
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Tabulated statistics of road networks at the level of intersections and for built-up areas for each decade from 1900 to 2010, and for 2015, for each core-based statistical area (CBSA, i.e., metropolitan and micropolitan statistical area) in the conterminous United States. These areas are derived from historical road networks developed by Johannes Uhl. See Burghardt et al. (2022) for details on the data processing.
Spatial coverage: all CBSAs that are covered by the HISDAC-US historical settlement layers.
This dataset includes around 2,700 U.S. counties. In the remaining counties, construction year coverage in the underlying ZTRAX data (Zillow Transaction and Assessment Dataset) is low. See Uhl et al. (2021) for details.
All data created by Keith A. Burghardt, USC Information Sciences Institute, USA
Codebook: these CBSA statistics are stratified by degree of aggregation.
- CBSA_stats_diffFrom1950: Change in CBSA-aggregated patch statistics between 1950 and 2015
- CBSA_stats_by_decade: CBSA-aggregated patch statistics for each decade from 1900-2010 plus 2015
- CBSA_stats_by_decade: CBSA-aggregated cumulative patch statistics for each decade from 1900-2010 plus 2015. All roads created up to a given decade are used for calculating statistics.
- Patch_stats_by_decade: Individual patch statistics for each decade from 1900-2010 plus 2015
- Patch_stats_by_decade: Individual cumulative patch statistics for each decade from 1900-2010 plus 2015. All roads created up to a given decade are used for calculating statistics.
The statistics are the following:
- msaid: CBSA code
- id: (if patch statistics) arbitrary int unique to each patch within the CBSA that year
- year: year of statistics
- pop: population within all CBSA counties
- patch_bupr: built up property records (BUPR) within a patch (or sum of patches within CBSA)
- patch_bupl: built up property l (BUPL) within a patch (or sum of patches within CBSA)
- patch_bua: built up area (BUA) within a patch (or sum of patches within CBSA)
- all_bupr: Same as above but for all data in 2015 regardless of whether properties were in patches
- all_bupl: Same as above but for all data in 2015 regardless of whether properties were in patches
- all_bua: Same as above but for all data in 2015 regardless of whether properties were in patches
- num_nodes: number of nodes (intersections)
- num_edges: number of edges (roads between intersections)
- distance: total road length in km
- k_mean: mean number of undirected roads per intersection
- k1: fraction of nodes with degree 1
- k4plus: fraction of nodes with degree 4+
- bearing: histogram of different bearings between intersections
- entropy: entropy of bearing histogram
- mean_local_gridness: Griddedness used in text
- mean_local_gridness_max: Same as griddedness used in text but assumes we can have up to 3 quadrilaterals for degree 3 (maximum possible, although intersections will not necessarily create right angles)
Code available at https://github.com/johannesuhl/USRoadNetworkEvolution.
References:
Burghardt, K., Uhl, J., Lerman, K., & Leyk, S. (2022). Road Network Evolution in the Urban and Rural United States Since 1900. Computers, Environment and Urban Systems.
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Abstract Intracellular signaling processes are frequently based on direct interactions between proteins and organelles. A fundamental strategy to elucidate the physiological significance of such interactions is to utilize optical dimerization tools. These tools are based on the use of small proteins or domains that interact with each other upon light illumination. Optical dimerizers are particularly suitable for reproducing and interrogating a given protein‐protein interaction and for investigating a protein's intracellular role in a spatially and temporally precise manner. Described in this article are genetic engineering strategies for the generation of modular light‐activatable protein dimerization units and instructions for the preparation of optogenetic applications in mammalian cells. Detailed protocols are provided for the use of light‐tunable switches to regulate protein recruitment to intracellular compartments, induce intracellular organellar membrane tethering, and reconstitute protein function using enhanced Magnets (eMags), a recently engineered optical dimerization system. © 2021 Wiley Periodicals LLC.
This article was corrected on 25 July 2022. See the end of the full text for details.
Basic Protocol 1 : Genetic engineering strategy for the generation of modular light‐activated protein dimerization unitsSupport Protocol 1 : Molecular cloningBasic Protocol 2 : Cell culture and transfectionSupport Protocol 2 : Production of dark containers for optogenetic samplesBasic Protocol 3 : Confocal microscopy and light‐dependent activation of the dimerization systemAlternate Protocol 1 : Protein recruitment to intracellular compartmentsAlternate Protocol 2 : Induction of organelles’ membrane tetheringAlternate Protocol 3 : Optogenetic reconstitution of protein functionBasic Protocol 4 : Image analysisSupport Protocol 3 : Analysis of apparent on‐ and off‐kineticsSupport Protocol 4 : Analysis of changes in organelle overlap over time -
Abstract This paper argues for a re‐examination of the nature and goals of broad computing education initiatives. Instead of starting with specific values or goals, we instead begin by considering various desired endpoints of computing instruction and then work backward to reason about what form learning activities might take and what are the underlying values and principles that support learners in reaching these endpoints. The result of this exercise is a push for rethinking the form of contemporary computing education with an eye toward more diverse, equitable and meaningful endpoints. With a focus on the role that constructionist‐focused pedagogies and designs can play in supporting these endpoints, we examine four distinct cases and the endpoints they support. This paper is not intended to encompass all the possible alternate endpoints for computer science education; rather, this work seeks to start a conversation around the nature of and need for alternate endpoints, as a means to re‐evaluate the current tools and curricula to prepare learners for a future of active and empowered computing‐literate citizens.
Practitioner notes What is already known about this topic
There is a growing call for computing education to be a core educational component.
Computing education traditionally has a narrow goal of training people for programming jobs.
Computing education fails to connect with students underrepresented in STEM.
What this paper adds
An argument for why we need more and diverse endpoints to computing education.
That many possible endpoints for computing education can be more inclusive, just and equitable than software engineering.
Constructionism is a particularly useful paradigm for approaching and supporting alternate endpoints.
Implications for practice and policy
Helps reframe the goals of computing education, to truly be “for all.”
Provides a set of cases for how this reframing can be achieved.
Gives policy new lenses for understanding, evaluating and implementing computing education.
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Abstract Vibrio parahaemolyticus is a Gram‐negative, halophilic bacterium and opportunistic pathogen of humans and shrimp. Investigating the mechanisms ofV. parahaemolyticus infection and the multifarious virulence factors it employs requires procedures for bacterial culture, genetic manipulation, and analysis of virulence phenotypes. Detailed protocols for growth assessment, generation of mutants, and phenotype assessment are included in this article. © 2020 Wiley Periodicals LLC.Basic Protocol 1 : Assessment of growth ofV. parahaemolyticus Alternate Protocol 1 : Assessment of growth ofV. parahaemolyticus using a plate readerBasic Protocol 2 : Swimming/swarming motility assayBasic Protocol 3 : Genetic manipulationAlternate Protocol 2 : Natural transformationBasic Protocol 4 : Secretion assay and sample preparation for mass spectrometry analysisBasic Protocol 5 : Invasion assay (gentamicin protection assay)Basic Protocol 6 : Immunofluorescence detection of intracellularV. parahaemolyticus Basic Protocol 7 : Cytotoxicity assay for T3SS2