Career Award Research Articles

Catalyst: The roles of chemistry in clean water for all

Dr. Young-Shin Jun is a professor in the Department of Energy, Environmental & Chemical Engineering and director of the Environmental NanoChemistry Laboratory at Washington University in St. Louis. She solves important energy and environmental challenges by using nanoscale interfacial reactions and nucleation. Her research interests in clean water include the development of novel materials, membrane processes, resource recovery, and managed aquifer recharge. She received a 2011 US National Science Foundation CAREER award, and she was named a 2015 Kavli Fellow by the US National Academy of Sciences, a 2016 Frontier of Engineering Fellow by the US National Academy of Engineering, and a 2019 American Chemical Society Fellow. Dr. Young-Shin Jun is a professor in the Department of Energy, Environmental & Chemical Engineering and director of the Environmental NanoChemistry Laboratory at Washington University in St. Louis. She solves important energy and environmental challenges by using nanoscale interfacial reactions and nucleation. Her research interests in clean water include the development of novel materials, membrane processes, resource recovery, and managed aquifer recharge. She received a 2011 US National Science Foundation CAREER award, and she was named a 2015 Kavli Fellow by the US National Academy of Sciences, a 2016 Frontier of Engineering Fellow by the US National Academy of Engineering, and a 2019 American Chemical Society Fellow. Reaction: Harnessing reactive oxygen species (ROS) for water purificationZhu et al.ChemJune 08, 2023In BriefReactive oxygen species (ROS) play a vital role in water purification. We outline their natural presence in the water matrix through a variety of chemical and photochemical processes and discuss advanced oxidation processes (AOPs) that draw inspiration from natural principles to boost ROS generation. Moreover, we summarize key challenges in ROS-based technologies for water and wastewater treatment, explain their fundamental origins, and propose strategies for minimizing energy and chemical usage while mitigating the formation of toxic byproducts. Full-Text PDF Reaction: Avoid fairy dust when engineering water-purification technologiesPaul WesterhoffChemJune 08, 2023In BriefThis Catalysis article discusses the risks of using nanomaterials for water purification and alternative strategies, painting a fuller picture of research in clean water. Full-Text PDF Molecular design of covalent organic frameworks for seawater desalination: A state-of-the-art reviewJrad et al.ChemMay 11, 2023In BriefConventional materials’ limitations are slowing the innovation in desalination to make it more accessible and energy efficient. Novel materials, such as covalent organic frameworks (COFs), provide design flexibility and could help achieve a breakthrough in desalination. This requires a comprehensive knowledge of desalination technologies and their technical challenges, as well as an understanding of the design principles of COFs. This report comprehensively discusses both of these issues while providing insights on how to design COFs for each specific desalination technology. Full-Text PDF

Combining activity-based protein profiling and flow cytometry to elucidate the role of lipid-metabolizing enzymes in cell heterogeneity

Abstract Cell metabolism is mediated by intracellular enzymes that supply essential and specific molecular cues needed to initiate the differentiation of homogenous cell populations into heterogenous cell populations. Intracellular enzymes involved in the metabolism of lipids are of particular interest as lipids play key roles in cell signaling and differing lipid-metabolizing enzyme activity may produce varying signaling profiles, and thus, a varying cell phenotype. To understand how these enzymes regulate function at the single-cell level, we aim to develop methodology that combines activity-based protein profiling (ABPP) and flow cytometry to allow for the separation of heterogenous cells into new populations based on enzyme activity. Our initial studies have focused on targeting serine hydrolases, as this family of enzymes includes numerous intracellular lipases involved with the metabolism of lipids. We have synthesized a modified activity-based fluorescent probe containing a triazole urea warhead known to label active serine hydrolases in live cells. Based on the fluorescent profile generated by measuring single cell fluorescence using flow cytometry, the probe targeted a select population of cells when compared to a control probe and unlabeled cells. This probe-labeled population was concentration dependent as higher concentration of probe labeled more enzyme, suggesting that a different population of cells could be collected between two different concentrations. After these cells are sorted based on the differing fluorescent signals, these new subsets will be analyzed via targeted lipidomics and proteomics methods to quantity any differences in the probed intracellular enzyme expression. This work was supported by the National Science Foundation CAREER Award no. 1942467.

Plasticity of clonal memory CD8 T cell differentiation

Abstract Memory CD8 T cells provide highly specific and long-lasting protection against previously experienced pathogens. This potent protection is mediated by hundreds to thousands of unique clones with distinct T cell receptors (TCRs). Higher T cell clonal diversity and recognition of a wider range of pathogen antigens are associated with improved host protection. Therefore, understanding how clonal responses are organized is important for improving T cell function in a range of diseases. To comprehensively test the range of clonal memory T cell differentiation capacity, we deeply profiled polyclonal mouse memory CD8 T cells from acute lymphocytic choriomeningitis virus (LCMV) infection before and after viral rechallenge by paired single cell RNA and TCR sequencing. We found that individual memory T cell clone expansion and differentiation at the peak of the rechallenge response is highly variable. Clones are spread across various patterns of unique phenotypes ranging from highly cytotoxic to stem-like memory states. To quantify clonal differentiation plasticity, we transferred memory T cells into multiple new congenic recipients. Clonal progeny in different hosts acquired highly similar differentiation states suggesting that emergent memory clone behavior is imprinted by events during the primary infection. Indeed, transcriptional state of clones prior to rechallenge was sufficient to predict clone behavior upon rechallenge. This work provides a platform for understanding the mechanisms by which memory T cells make decisions and future studies will aim to perturb clones to elicit specific functions during a memory response. Supported by grants from the Burroughs Wellcome Fund (Career Award for Medical Scientists [ATS]), Cancer Research Institute (Technology Impact Award, Lloyd J. Old STAR Award [ATS]), American Society of Hematology (ASH Scholar Award [ATS]), Parker Institute for Cancer Immunotherapy (ATS), Stanford School of Medicine (Propel Postdoctoral Scholarship [KHG]), National Institutes of Health (5T32AI007290-38 [CJR])

Paramagnetic rim lesions predict the development of clinical MS in radiologically isolated syndrome: results from a prospective cohort study (S27.003)

Paramagnetic rim lesions predict the development of clinical MS in radiologically isolated syndrome: results from a prospective cohort study (S27.003)

Metabolomic Profiling of Multiple Sclerosis Lesions and Periplaque White Matter Demonstrates Extensive Changes in Lipid Metabolism (P2-3.010)

<h3>Objective:</h3> To identify whether there are differences between the brain tissue metabolome in people with multiple sclerosis (PwMS) compared to controls and between the different type of MS lesions <h3>Background:</h3> MS is characterized by immune-mediated white matter (WM) demyelination and consecutive axonal loss. Whether this process alters the metabolome in the affected brain areas is not clear. <h3>Design/Methods:</h3> Brain tissues, obtained from 5 PwMS and 12 controls, were sent for metabolomic analysis. In PwMS, tissues were extracted from the edge and core of demyelinated WM chronic active and inactive lesions, and periplaque WM, while in controls they were dissected from normal WM. Weighted gene correlation network analysis (WGCNA) were utilized to cluster highly correlated metabolites together into modules. We then applied generalized estimating equations models to compare WGCNA-module scores between different tissues, accounting for multiple metabolomic profiles contributed by some subjects. <h3>Results:</h3> MS lesions were found to have decreased concentrations of hexosylceramides (p = 0.019), glycero-phospholipids (p = 3.6E−7), nucleotide metabolites (p = 5.0E−4), and long-chain fatty acids (p = 1.6E−6) and increased concentrations of dipeptides/sugars (p = 0.0063), sphingosines (p = 0.0026), phospholipids (p = 0.0019), sphingomyelines and ceramides (p = 4.4E−10) compared to control WM. In MS periplaques there were decreased levels of glycerol-phospholipids (p = 0.017) and long-chain fatty acids (p = 0.014) and increased levels of sphingomyelines and ceramides (p = 0.0026) compared to control WM. <h3>Conclusions:</h3> Myelin lipids were significantly altered in MS with more prominent differences in lesions, and these could potentially act as biomarkers of inflammation and neurodegeneration in PwMS. <b>Disclosure:</b> Dr. Ladakis has nothing to disclose. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata Therapeutics. The institution of Dr. Absinta has received research support from International MS Alliance. The institution of Dr. Absinta has received research support from FRRB Early Career Award. The institution of Dr. Absinta has received research support from Cariplo Foundation. Dr. Reyes-Mantilla has nothing to disclose. The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research . The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.

Imaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative (P11-3.009)

Imaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative (P11-3.009)

The Power to Reward vs. the Power to Punish: The Influence of Power Framing on Individual-Level Exploration

This article adopts a relational perspective to demonstrate that characteristics of the dyadic relationship between supervisors and their employees are critical to understanding individual-level exploration—understood as the extent to which organizational members pursue new opportunities and experiment with changes to current practices. To this end, we introduce the concept of power framing—that is, whether the control over valued resources is emphasized as the ability to reward or to punish—and propose that supervisor power framing shapes employee exploration. In an experimental study, we demonstrate that reward (versus punishment) power framing increases employee exploration behavior and that this effect is mediated by perceived trustworthiness of the supervisor. In a second survey study, we replicate these findings in a field sample and show that the relationship between reward power framing and exploration depends on the degree to which the focal employee is sensitive to power characteristics (i.e., power distance orientation). This investigation advances scholarship on the microfoundations of exploration while also highlighting the ability of leaders to alter trustworthiness perceptions and induce employee exploration through power framing. Funding: This work was supported by a National Science Foundation CAREER Award from the Directorate for Social, Behavioral and Economic Sciences [Grant 1943688] granted to O. Schilke. Additional funding was provided by the Sauder School of Business, University of British Columbia. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2023.1672 .

The ASPHO 2023 Distinguished Career Award goes to Dr. A. Kim Ritchey.

The author declares no conflict of interests. The data that support the findings of this study are available from the corresponding author upon reasonable request.

The association between unpaid labour and mental health in working-age adults in Australia from 2002 to 2020: a longitudinal population-based cohort study.

Unpaid labour is a daily part of most people's lives, none more so than for women. Yet, in comparison to paid work, the effect of unpaid labour on mental health is an under-researched area. This study aims to address key gaps in the extant literature, examining how unpaid labour is associated with mental health in working-age men and women, and whether gender differences exist. In this longitudinal population-based cohort study, 19 waves of the Household, Income, and Labour Dynamics in Australia (HILDA) survey were used to employ a fixed effects regression analysis to examine the associations between unpaid labour and mental health in working-age (aged 25-64 years) Australian adults. Mental health was assessed using the MHI-5 scale. Both the individual and the combined effects of four different domains of unpaid labour (household work, childcare, care for adults, and outdoor tasks) were interrogated, as were the gender differences. Of the 37 352 participants (297 036 observations) in waves 2002-20 of the HILDA Survey, 22 832 people (190 207 observations) were aged 25-64 years, and after excluding participants with missing data, 21 014 participants (150 163 observations) were included in the analysis. Increasing time in household work was negatively associated with mental health in both men (β coefficient=-0·026 [95% CI -0·04 to -0·01]) and women (β coefficient=-0·009 [-0·02 to 0·001]), as was care for adults (disabled or older people) in women (β coefficient=-0·027 [-0·04 to -0·01]). Conversely, increasing time in childcare for women (β coefficient=0·016 [0·01 to 0·02]) and outdoor tasks for men, was positively associated with mental health (β coefficient=0·067 [0·04 to 0·09]). A null finding for the overall cumulative total unpaid labour exposure for both men and women was probably attributable to the opposing direction of effects between the individual domains that constituted the total load. This study reveals considerable variance and nuance in how different domains of unpaid labour affect mental health, as well as continued inequity in the division of unpaid labour in households, with women doing considerably more unpaid labour than men. This study also exposes important challenges associated with measuring and understanding total (combined) unpaid labour as a determinant of health. University of Melbourne Research Training Scholarship, Australian Research Council Discovery Early Career Award, Australian Research Council Linkage Project.

Special Collection on Organic Electrocatalysis

Special Collection on Organic Electrocatalysis

Introduction to Michael A. Hogg's SPSSI Kurt Lewin Award Address

Introduction to Michael A. Hogg's SPSSI Kurt Lewin Award Address

A176 ASSOCIATIONS OF ANTIBIOTICS, HORMONAL THERAPIES, ORAL CONTRACEPTIVES, AND LONG-TERM NSAIDS WITH INFLAMMATORY BOWEL DISEASE: RESULTS FROM THE PROSPECTIVE URBAN RURAL EPIDEMIOLOGY (PURE) STUDY

A176 ASSOCIATIONS OF ANTIBIOTICS, HORMONAL THERAPIES, ORAL CONTRACEPTIVES, AND LONG-TERM NSAIDS WITH INFLAMMATORY BOWEL DISEASE: RESULTS FROM THE PROSPECTIVE URBAN RURAL EPIDEMIOLOGY (PURE) STUDY

Assortment Planning for Recommendations at Checkout Under Inventory Constraints

In this paper, we consider a personalized assortment planning problem under inventory constraints, where each arriving customer type is defined by a primary item of interest. As long as that item is in stock, the customer adds it to the shopping cart, at which point the retailer can recommend to the customer an assortment of add-ons to go along with the primary item. This problem is motivated by the new “recommendation at checkout” systems that have been deployed at many online retailers, and it also serves as a framework that unifies many existing problems in online algorithms (e.g., personalized assortment planning, single-leg booking, and online matching with stochastic rewards). In our problem, add-on recommendation opportunities are eluded when primary items go out of stock, which poses additional challenges for the development of an online policy. We overcome these challenges by introducing the notion of an inventory protection level in expectation and derive an algorithm with a 1/4-competitive ratio guarantee under adversarial arrivals. Funding: This work was supported by the Adobe Data Science Research Award and the Alibaba Innovation Research Award. L. Xin was partly supported by the National Science Foundation (NSF) [Award CMMI-1635160], X. Chen was supported by the NSF [CAREER Award IIS-1845444]. W. Ma and D. Simchi-Levi were supported by the Accenture and MIT Alliance in Business Analytics.

The Dual Function of Organizational Structure: Aggregating and Shaping Individuals’ Votes

How do organizational structures influence organizational decision making? This article reveals organizational structures’ dual function: they both (1) aggregate and (2) shape individuals’ decisions. What makes this dual function so remarkable is that the two effects are diametrically opposed to one another. Ceteris paribus, a less stringent decision-making structure reduces the amount of support required for a given project to be greenlit at the organizational level, which should result in more investments getting approved. However, we find that this ceteris paribus assumption does not hold, because a less stringent decision-making structure also reduces individuals’ tendency to provide their support for an investment. Our experimental investigation of organizational voting provides evidence for our position that organizational structure plays an important role beyond mere aggregation: voting thresholds also affect individuals’ voting behavior. The combination of both effects explains why the organizational adoption of a new voting threshold may not yield the intended outcome.Funding: This work was supported by a National Science Foundation CAREER Award from the Directorate for Social, Behavioral and Economic Sciences [Grant 1943688] granted to O. Schilke.Supplemental Material: The online appendices are available at https://doi.org/10.1287/orsc.2023.1653 .

Theory and computation early career award talk: unraveling the CRISPR-Cas revolution through the lens of computational biophysics.

The clustered regularly interspaced short palindromic repeat (CRISPR) genome-editing revolution established the beginning of a new era in life sciences. I will report the role of state-of-the-art computations in the CRISPR-Cas9 revolution, from the early refinement of cryo-EM data to enhanced simulations of large-scale conformational transitions. Molecular simulations reported a mechanism for RNA binding and the formation of a catalytically competent Cas9 enzyme, corroborated by recent cryo-EM data of the activated state. Inspired by single-molecule experiments, molecular dynamics offered a rationale for the onset of off-target effects, while graph theory unveiled the allosteric regulation. Finally, the use of a mixed quantum-classical approach established the catalytic mechanism of DNA cleavage. Overall, molecular simulations have been instrumental in understanding the dynamics and mechanism of CRISPR-Cas9, contributing to understanding function, catalysis, allostery, and specificity. Future computational studies will bridge the scales from quantum mechanical approaches to enhanced simulations and cryo-EM processing methods to push the boundaries of molecular simulations and tackle the most exciting problems in the biophysics of genome editing.

A Time of Change

A Time of Change

Process evaluation of an academic dissemination and implementation science capacity building program.

The UC San Diego Altman Clinical and Translational Research Institute Dissemination and Implementation Science Center (DISC) launched in 2020 to provide dissemination and implementation science (DIS) training, technical assistance, community engagement, and research advancement. DISC developed a program-wide logic model to inform a process evaluation of member engagement and impact related to DISC services. The DISC Logic Model (DLM) served as the framework for a process evaluation capturing quantitative and qualitative information about scientific activities, outputs, and outcomes. The evaluation involved a multimethod approach with surveys, attendance tracking, feedback forms, documentation of grant outcomes, and promotions metrics (e.g., Twitter engagement). There were 540 DISC Members at the end of year 2 of the DISC. Engagement in the DISC was high with nearly all members endorsing at least one scientific activity. Technical assistance offerings such as DISC Journal Club and consultation were most frequently used. The most common scientific outputs were grant submission (65, 39%), formal mentoring for career award (40, 24%), and paper submission (34, 21%). The DLM facilitated a comprehensive process evaluation of our center. Actionable steps include prioritizing technical assistance, strengthening networking opportunities, identifying streamlined approaches to facilitate DIS grant writing through writing workshops, as well as "office hours" or organized writing leagues.

One-Way Functions and (Im)perfect Obfuscation

A program obfuscator takes a program and outputs a “scrambled” version of it, where the goal is that the obfuscated program will not reveal much about its structure beyond what is apparent from executing it. There are several ways of formalizing this goal. Specifically, in indistinguishability obfuscation, first defined by Barak et al. (CRYPTO 2001), the requirement is that the results of obfuscating any two functionally equivalent programs (circuits) will be computationally indistinguishable. Recently, a fascinating candidate construction for indistinguishability obfuscation was proposed by Garg et al. (FOCS 2013). This has led to a flurry of discovery of intriguing constructions of primitives and protocols whose existence was not previously known (for instance, fully deniable encryption by Sahai and Waters, STOC 2014). Most of them explicitly rely on additional hardness assumptions, such as one-way functions. Our goal is to get rid of this extra assumption. We cannot argue that indistinguishability obfuscation of all polynomial-time circuits implies the existence of one-way functions, since if P = NP, then program obfuscation (under the indistinguishability notion) is possible. Instead, the ultimate goal is to argue that if P 6= NP and program obfuscation is possible, then one-way functions exist. Our main result is that if NP 6⊆ io-BPP and there is an efficient (even imperfect) indistinguishability obfuscator, then there are one-way functions. In addition, we show that the existence of an indistinguishability obfuscator implies (unconditionally) the existence of SZKarguments for NP. This, in turn, provides an alternative version of our main result, based on the assumption of hard-on-the average NP problems. To get some of our results we need obfuscators for simple programs such as 3CNF formulas. ∗This paper incorporates the manuscript of Moran and Rosen [MR13]. †Weizmann Institute of Science. Email: {ilan.komargodski,moni.naor,eylon.yogev}@weizmann.ac.il. Supported in part by a grant from the I-CORE Program of the Planning and Budgeting Committee, the Israel Science Foundation, BSF, IMOS and the Citi Foundation. Moni Naor is the incumbent of the Judith Kleeman Professorial Chair. ‡IDC Herzliya. Email: talm@idc.ac.il. Supported by ISF grant no. 1790/13 and by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 293843 §Cornell University. Email: rafael@cs.cornell.edu. Supported in part by a Alfred P. Sloan Fellowship, Microsoft New Faculty Fellowship, NSF Award CNS1217821, NSF CAREER Award CCF-0746990, NSF Award CCF-1214844, AFOSR YIP Award FA9550-10-1-0093, and DARPA and AFRL under contract FA8750-11-20211. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Defense Advanced Research Projects Agency or the US Government. ¶IDC Herzliya. Email: alon.rosen@idc.ac.il. Supported by ISF grant no. 1255/12 and by the ERC under the EU’s Seventh Framework Programme (FP/2007-2013) ERC Grant Agreement n. 307952.

A Conversation with … Cecilia Aragon PhD, Champion Aerobatic Pilot, on Grace Under Pressure.

A Conversation with … Cecilia Aragon PhD, Champion Aerobatic Pilot, on Grace Under Pressure.

How Did They Get There? What Perspectives From the Top Tell Us About Developing Women Leaders in Academic Anesthesiology.

How Did They Get There? What Perspectives From the Top Tell Us About Developing Women Leaders in Academic Anesthesiology.