Publications

CCDC 2045457: Experimental Crystal Structure Determination

An Activity-Based Methionine Bioconjugation Approach To Developing Proximity-Activated Imaging Reporters

Chemical probes that report on protein activity, rather than protein abundance, with spatial and temporal resolution can enable studies of their native function in biological contexts as well as provide opportunities for developing new types of biochemical reporters. Here we present a sensing platform, termed proximity-activated imaging reporter (PAIR), which combines activity-based methionine bioconjugation and antibody labeling with proximity-dependent oligonucleotide-based amplification to monitor dynamic changes of a given analyte in cells and animals through context-dependent methionine labeling of specific protein targets. We establish this PAIR method to develop sensors for imaging reactive oxygen species (ROS) and calcium ions through oxaziridine-directed labeling of reactive methionine residues on β-actin and calmodulin (CaM), respectively, where the extent of methionine bioconjugation on these protein targets can serve as an indicator of oxidative stress or calcium status. In particular, application of PAIR to activity-based CaM detection provides a method for imaging integrated calcium activity in both in vitro cell and in vivo zebrafish models. By relying on native protein biochemistry, PAIR enables redox and metal imaging without introduction of external small molecules or genetically encoded indicators that can potentially buffer the natural/existing pools. This approach can be potentially generalized to target a broader range of analytes by pairing appropriate activity-based protein probes with protein detection reagents in a proximity-driven manner, providing a starting point not only for designing new sensors but also for monitoring endogenous activity of specific protein targets in biological specimens with spatial and temporal fidelity.

ChemInform Abstract: Gold‐Catalyzed [3 + 3]‐Annulation of Azomethine Imines with Propargyl Esters.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Accidental torsion in buildings due to stiffness uncertainty

Abstract Discrepancies between the computed and actual values of the structural element stiffness imply that a building with nominally symmetric plan is actually asymmetric to some unknown degree and will undergo torsional vibration when subjected to purely translational ground motion. Such accidental torsion leads to increase in structural element deformations which is shown to be essentially insensitive to the uncoupled lateral vibration period of the system but is affected strongly by the ratio of uncoupled lateral and torsional vibration periods. The structural deformations increase, in the mean, by at most 10 and 5 per cent for R/C and steel buildings, respectively, and by much smaller amounts for a wide range of system parameters. The increase in structural deformations due to stiffness uncertainty is shown to be much smaller than implied by the accidental torsional provisions in the Uniform Building Code and most other building codes.

Uniform-size hydrophobic polymer-based separation media selectively modified with a hydrophilic external polymeric layer

A simple procedure for the preparation of macroporous hydrophobic styrene-divinylbenzene polymeric separation media with a hydrophilic outer surface has been developed. A hydrophilic monomer and water-soluble polymerization initiator are added to the reaction mixture during the final polymerization step of the preparation of size-monodisperse particles. Because the hydrophobic styrene-divinylbenzene framework of the beads is already formed, and the hydrophilic monomer does not penetrate the pores of the beads that are filled with a hydrophobic porogen, the hydrophilic layer is formed only at the surface of the beads. The hydrophilic monomers used included glycerol monomethacrylate and glycerol dimethacrylate and toluene was used as the porogen for the poly(styrene-co-divinylbenzene) beads. Comparative experiments involving beads with or without a hydrophilic medium showed that the separation selectivity of the media towards hydrophobic solutes remains unchanged. However, the modified medium with a hydrophilic layer could be used to analyse mixtures that also contained large peptide molecules as these do not adsorb at its surface as is the case with the unmodified hydrophobic beads.

Monotasks

In today's data analytics frameworks, many users struggle to reason about the performance of their workloads. Without an understanding of what factors are most important to performance, users can't determine what configuration parameters to set and what hardware to use to optimize runtime. This paper explores a system architecture designed to make it easy for users to reason about performance bottlenecks. Rather than breaking jobs into tasks that pipeline many resources, as in today's frameworks, we propose breaking jobs into monotasks: units of work that each use a single resource. We demonstrate that explicitly separating the use of different resources simplifies reasoning about performance without sacrificing performance. Monotasks provide job completion times within 9% of Apache Spark for typical scenarios, and lead to a model for job completion time that predicts runtime under different hardware and software configurations with at most 28% error. Furthermore, separating the use of different resources allows for new optimizations to improve performance.

Progress, Challenges, and Opportunities with Artificial Metalloenzymes in Biosynthesis

In this Perspective, we present progress, outstanding challenges, and opportunities for the incorporation of artificial metalloenzymes (ArMs) into biosynthetic pathways. We first explain discoveries within the field of ArMs that led to the potential inclusion of these enzymes in biosynthesis. We then describe the specific barriers that our laboratory, in collaboration with the laboratories of Keasling and Mukhopadhyay, addressed to establish a biosynthetic pathway containing an ArM. This biosynthesis produced an unnatural cyclopropyl terpenoid by combining heterologous production of the terpene with modification of its terminal alkene by an ArM built from a cytochrome P450. Finally, we describe the remaining challenges and opportunities related to the application of ArMs in synthetic biology.

A Pilot Trial for Midlife and Older Adults: Sleep and Circadian Treatment Plus Memory Support and Boosters

Although comparisons with control conditions and larger samples are needed, TSC+MSI and booster messages may improve sleep and circadian and related outcomes among midlife and older adults.

LOSS Transient Discovery Report for 2016-09-22

CCDC 1966162: Experimental Crystal Structure Determination

The External Impact of China's Exchange Rate Policy: Evidence from Firm Level Data

Neural Packet Classification

Packet classification is a fundamental problem in computer networking. This problem exposes a hard tradeoff between the computation and state complexity, which makes it particularly challenging. To navigate this tradeoff, existing solutions rely on complex hand-tuned heuristics, which are brittle and hard to optimize. In this paper, we propose a deep reinforcement learning (RL) approach to solve the packet classification problem. There are several characteristics that make this problem a good fit for Deep RL. First, many of the existing solutions are iteratively building a decision tree by splitting nodes in the tree. Second, the effects of these actions (e.g., splitting nodes) can only be evaluated once we are done with building the tree. These two characteristics are naturally captured by the ability of RL to take actions that have sparse and delayed rewards. Third, it is computationally efficient to generate data traces and evaluate decision trees, which alleviate the notoriously high sample complexity problem of Deep RL algorithms. Our solution, NeuroCuts, uses succinct representations to encode state and action space, and efficiently explore candidate decision trees to optimize for a global objective. It produces compact decision trees optimized for a specific set of rules and a given performance metric, such as classification time, memory footprint, or a combination of the two. Evaluation on ClassBench shows that NeuroCuts outperforms existing hand-crafted algorithms in classification time by 18% at the median, and reduces both time and memory footprint by up to 3x.

Understanding the Cathode Electrochemistry of Humidified Solid‐State Lithium‐Oxygen Batteries

Abstract Lithium‐oxygen batteries (LOBs) possess a high theoretical energy density, making them potential candidates for next‐generation energy storage. However, challenges such as reactive oxygen species‐induced component degradation hinder their practical use. Inorganic solid‐state electrolytes offer an alternative to degradation‐prone aprotic electrolytes, while also protecting lithium anodes from potential atmospheric reactants. This study explores the cathode electrochemistry of solid‐state LOBs using humidified oxygen, which forms an aqueous catholyte during initial cycling, thereby improving cathode‐electrolyte contact. To quantitatively analyze the cathode electrochemistry, a ‘Humidity‐Incorporated’ Differential Electrochemical Gas Monitoring System (HiDEMS) is developed to control humidity and monitor gas consumption and evolution in real time. When studying a Li‐O 2 cell that employs a NASICON‐type Li 1.3 Al 0.3 Ti 1.7 (PO 4 ) 3 (LATP) solid electrolyte and a porous carbon cathode, a shift in discharge products from Li 2 O 2 to LiOH is observed over repeated cycles. While Li 2 O 2 evolves O 2 during charging, LiOH oxidation leads to minimal O 2 release and increased CO 2 production, originating from oxidation of carbon electrodes. Further, dissolution of Al and P from LATP is observed, likely driven by the formation of the alkaline catholyte. The findings highlight the need for carbon‐free cathode materials and more stable solid‐state conductors to minimize side reactions and improve rechargeability in humidified solid‐state Li‐O 2 batteries.

Argon diffusion in pyroxenes: Implications for thermochronometry and mantle degassing

Palladium-Catalyzed Amination of Aryl Halides with Aqueous Ammonia and Hydroxide Base Enabled by Ligand Development

The conversion of aryl halides to primary arylamines with a convenient and inexpensive source of ammonia has been a long-standing synthetic challenge. Aqueous ammonia would be the most convenient and least expensive form of ammonia, but such a palladium-catalyzed amination reaction with a high concentration of water faces challenges concerning catalyst stability and competing hydroxylation, and palladium-catalyzed reactions with this practical reagent are rare. Further, most reactions with ammonia to form primary amines are conducted with <i>tert</i>-butoxide base, but reactions with ammonium hydroxide would contain hydroxide as base. Thus, ammonia surrogates, ammonia in organic solvents, and ammonium salts have been used under anhydrous conditions instead with varying levels of selectivity for the primary amine. We report the palladium-catalyzed amination of aryl and heteroaryl chlorides and bromides with aqueous ammonia and a hydroxide base to form the primary arylamine with high selectivity. The palladium catalyst containing a new dialkyl biheteroaryl phosphine ligand (KPhos) suppresses both the formation of aryl alcohol and diarylamine side products. Mechanistic studies with a soluble hydroxide base revealed turnover-limiting reductive elimination of the arylamine and an equilibrium between arylpalladium amido and hydroxo complexes prior to the turnover-limiting step.

Towards up-scaling restored wetland CO 2 and CH 4 exchange in the Sacramento - San Joaquin River Delta

Low energy electron diffraction (LEED) study of the adsorption of acetic acid and propanoic acid on Ag(111) and Pt(111)

The adsorption of acetic acid and of propanoic acid on Ag(111) and Pt(111) single crystal surfaces has been studied with LEED. Both acetic acid and propanoic acid formed two-dimensional structures in two different types of orientation on Ag(111) and propanoic acid apparently formed the same structure on graphite covered Pt(111). Neither acid formed ordered monolayers when adsorbed on clean Pt(111). The similar LEED data and physical properties of the acid molecules suggested similar structures for both acids consisting of closely packed arrays of hydrogen-bonded dimers.

ChemInform Abstract: Complexes of Earth‐Abundant Metals for Catalytic Electrochemical Hydrogen Generation under Aqueous Conditions

Abstract Review: 105 refs.