cssi/SciSciGPT-SciSciNet huggingface dataset:
The Design Principles of Biochemical Timers: Circuits That Discriminate Between Transient and Sustained Stimulation

Summary Many cellular responses for which timing is critical display temporal filtering—the ability to suppress response until stimulated for longer than a given minimal time. To identify biochemical circuits capable of kinetic filtering, we comprehensively searched the space of three-node enzymatic networks. We define a metric of “temporal ultrasensitivity,” the steepness of activation as a function of stimulus duration. We identified five classes of core network motifs capable of temporal filtering, each with distinct functional properties such as rejecting high-frequency noise, committing to response (bistability), and distinguishing between long stimuli. Combinations of the two most robust motifs, double inhibition (DI) and positive feedback with AND logic (PFAND), underlie several natural timer circuits involved in processes such as cell cycle transitions, T cell activation, and departure from the pluripotent state. The biochemical network motifs described in this study form a basis for understanding common ways cells make dynamic decisions.
Random norming aids analysis of non-linear regression models with sequential informative dose selection

Abstract A two-stage adaptive optimal design is an attractive option for increasing the efficiency of clinical trials. In these designs, based on interim data, the locally optimal dose is chosen for further exploration, which induces dependencies between data from the two stages. When the maximum likelihood estimator (MLE) is used under nonlinear regression models with independent normal errors in a pilot study where the first stage sample size is fixed, and the second stage sample size is large, the Fisher information fails to normalize the estimator adequately asymptotically, because of dependencies. In this situation, three alternative random information measures are presented and are shown to provide better normalization of the MLE asymptotically. The performance of random information measures is investigated in simulation studies, and the results suggest that the observed information performs best when the sample size is small.
Positive urgency worsens the impact of normative feedback on 21st birthday drinking

Abstract Background The 21st birthday is associated with more alcohol consumption and negative consequences than any other occasion. The current study investigated how positive urgency, the tendency to act rashly in response to positive emotions, influences 21st birthday drinking and the effectiveness of a single event text message intervention designed to reduce 21st birthday drinking and related negative consequences. Methods Participants were 183 undergraduate students (69% female, 86% white) about to turn 21. Participants were randomly assigned to either a text message intervention or control condition. Those in the intervention condition received one text message the day before their 21st birthday that provided personalized normative feedback and one text message on the day of their 21st birthday. Participants reported actual alcohol consumption the day after their 21st birthday celebration. Results Hierarchical linear regression found that, after controlling for sex, intervention condition, and planned drinking, positive urgency was associated with greater number of drinks (β = .15, p = .031) and drinking problems (β = .25, p = .001). A moderated-mediation model was significant (B = 0.42, CI95 [.10, .76]): At high levels of positive urgency, the intervention condition was associated with drinking more than planned, which significantly mediated the relationship between intervention and alcohol-related consequences; the mediation was not significant at mean or low levels of positive urgency. Conclusions These findings are the first to link positive urgency with 21st birthday drinking and to empirically demonstrate that positive urgency negatively impacts the effectiveness of an intervention aimed at reducing alcohol consumption.
Beyond beaconing: Emerging applications and challenges of BLE

Abstract As an emerging technology with exceptional low energy consumption and low-latency data transmissions, Bluetooth Low Energy (BLE) has gained significant momentum in various application domains, such as Indoor Positioning, Home Automation, and Wireless Personal Area Network (WPAN) communications. With various novel protocol stack features, BLE is finding use on resource-constrained sensor nodes as well as more powerful gateway devices. Particularly proximity detection using BLE beacons has been a popular usage scenario ever since the release of Bluetooth 4.0, primarily due to the beacons’ energy efficiency and ease of deployment. However, with the rapid rise of the Internet of Things (IoT), BLE is likely to be a significant component in many other applications with widely varying performance and Quality-of-Service (QoS) requirements and there is a need for a consolidated view of the role that BLE will play in applications beyond beaconing. This paper comprehensively surveys state-of-the-art applications built with BLE, obstacles to adoption of BLE in new application areas, and current solutions from academia and industry that further expand the capabilities of BLE.
On the Fundamental Limits of Multi-user Scheduling under Short-term Fairness Constraints

In the conventional information theoretic analysis of multiterminal communication scenarios, it is often assumed that all of the distributed terminals use the communication channel simultaneously. However, in practical wireless communication systems — due to restricted computation complexity at network terminals — a limited number of users can be activated either in uplink or downlink simultaneously. This necessitates the design of a scheduler which determines the set of active users at each time-slot. A well-designed scheduler maximizes the average system utility subject to a set of fairness criteria, which must be met in a limited window-length to avoid long starvation periods. In this work, scheduling under short-term temporal fairness constraints is considered. The objective is to maximize the average system utility such that the fraction of the time-slots that each user is activated is within desired upper and lower bounds in the fairness window-length. The set of feasible window-lengths is characterized as a function of system parameters. It is shown that the optimal system utility is non-monotonic and super-additive in window-length. Furthermore, a scheduling strategy is proposed which satisfies short-term fairness constraints for arbitrary window-lengths, and achieves optimal average system utility as the window-length is increased asymptotically. Numerical simulations are provided to verify the results.
Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities.

Non-neuronal optogenetic approaches empower precise regulation of protein dynamics in live cells but often require target-specific protein engineering. To address this challenge, we developed a gen...
The Educational Gradient in Health Among Children in Immigrant Families

Educational inequality in the health of US children—what social scientists refer to as the “educational gradient” in health—is present at birth for virtually every marker of health and increases throughout childhood. However, a puzzling contradiction to this pattern has been observed among the growing population of youth in immigrant families. Some evidence suggests an ambiguous relationship between education and health among immigrant families, with a flat relationship between maternal education and maternal health behaviors and children’s birth outcomes, and a stronger relationship as children become adolescents. Does an educational gradient in health emerge among children in immigrant families during childhood and adolescence? To date, we lack a prospective examination of how the gradient changes from birth throughout childhood and adolescence among this population. Moreover, while the dominant explanation for a weaker gradient among children with immigrant parents centers on the family setting, we know little about family-level dynamics among the same immigrant families as children age. Using national, longitudinal data from the Fragile Families and Child Well-Being Study, we examine the association between maternal education and children’s health (measured by mothers’ ratings) over the early life course (birth through age 15) among children of immigrants and children of native-born parents and consider whether changes in children’s economic status and family composition contribute to the educational gradient, or lack thereof, in child health. Analyses reveal that: (1) maternal education is strongly predictive of health, even among children of immigrants; (2) immigrant status does not appear to be protective for health within educational groups, as evidenced by poorer health among children of immigrants whose mothers have the lowest level of education, as compared to children of natives; (3) children in the least-educated immigrant families are experiencing better health trajectories as they age than children in similar native-born families; and (4) accounting for household economic conditions and family composition does not reduce the size of the education gradient over time among children of immigrants.
The Effect of Hurricane Irma Storm Surge on the Freshwater Lens in Big Pine Key, Florida using Electrical Resistivity Tomography

Animals and plants on low elevation oceanic islands often rely on a thin lens of fresh groundwater and this lens is vulnerable to seawater contamination from storm surge. Documentation of the impact of the storm surge on the freshwater lens and its subsequent recovery is limited. In September 2017, Hurricane Irma made landfall in the Florida Keys as a category 4 storm with storm surge heights in excess of 2 m. This study used Electrical Resistivity Tomography (ERT) to investigate the effect of the storm surge on the freshwater lens of Big Pine Key, FL. The study compared ERT images along three profiles ranging between 220 and 280 m length collected in 2011 with post storm data collected about 3 to 4 months (November 2017/January 2018) and eight (May 2018) months after Irma. The post storm data documented that the storm surge impacted the freshwater lens on all three profiles with low resistivity (i.e., high salinity) zones in the upper 2 m of the groundwater. The increase in salinity was most pronounced in the lower elevations of the profiles. The May 2018 data were collected immediately after 2 weeks of intense precipitation. These data showed 40% recovery of the freshwater lens, most pronounced in the lower elevation of the profiles. This suggests that both the impact of storm surge and the freshwater recovery due to precipitation are most pronounced in low elevation regions where both saline and freshwater can collect at the surface.
Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation

Abstract Remyelination failure is a crucial component of disease progression in the autoimmune demyelinating disease Multiple Sclerosis (MS). The regenerative capacity of oligodendrocyte progenitor cells (OPCs) to replace myelinating oligodendrocytes is likely influenced by many aspects of the lesion environment including inflammatory signaling and extracellular matrix (ECM) deposition. These features of MS lesions are typically attributed to infiltrating leukocytes and reactive astrocytes. Here we demonstrate that fibroblasts also contribute to the inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1GFP transgenic mice, we show that perivascular fibroblasts are activated in the spinal cord at EAE onset, and infiltrate the parenchyma by the peak of behavioral deficits where they are closely associated with areas of demyelination, myeloid cell accumulation, and ECM deposition. We further show that both fibroblast conditioned media and fibroblast ECM inhibit the differentiation of OPCs into mature oligodendrocytes. Taken together, our results indicate that the fibrotic scar is a major component of EAE pathology that leads to an inhibitory environment for remyelination, thus raising the possibility that anti-fibrotic mechanisms may serve as novel therapeutic targets for MS.
HOME CARE NURSES CLAIM MEDICARE IGNORES SOCIAL DETERMINANTS OF HEALTH

There is significant literature on the importance of addressing social determinants of health (SDOH) in order to improve health care outcomes. In response, the Centers for Medicare and Medicaid Ser...
IEEE 1588-Based Synchronization System for a Displacement Sensor Network

Distribution of precise time reference in an Ethernet network allows the implementation of distributed measurement systems, overcoming the limitations of a complex architecture. This paper deals with a displacement sensor network that is built over Ethernet and synchronized according to IEEE 1588. Measurement devices share the same time reference, enabling accurate calculation of cross-derived quantities (multidimensional speed and acceleration). In this paper, a description of the sensor architecture is given, and attention is focused on the IEEE 1588 implementation. In particular, the proposed low-cost system does not use any dedicated synchronization hardware, but it can reduce the deviation from time reference down to 20 .
Correlation of accelerometer and microphone data in the "coin tap test"

In the "coin tap test," an operator taps with a coin-like light tool on the structure to be inspected, feeling the subtle difference of impact force and hearing the resulting sound to discriminate defective regions from normal ones. The test remains largely subjective, and there has been considerable uncertainty about the physical principles behind it. Analyzing and comparing the force measured by an accelerometer in the hammer and the resulting sound recorded with a microphone, this paper seeks an understanding of the fundamental principles underlying the individual measurement techniques. It gives a paradigm for sensor fusion via using the data from one modality to select the optimal time window for signal analysis of another modality.
Spectral State Compression of Markov Processes

Model reduction of Markov processes is a basic problem in modeling state-transition systems. Motivated by the state aggregation approach rooted in control theory, we study the statistical state compression of a discrete-state Markov chain from empirical trajectories. Through the lens of spectral decomposition, we study the rank and features of Markov processes, as well as properties like representability, aggregability, and lumpability. We develop spectral methods for estimating the transition matrix of a low-rank Markov model, estimating the leading subspace spanned by Markov features, and recovering latent structures like state aggregation and lumpable partition of the state space. We prove statistical upper bounds for the estimation errors and nearly matching minimax lower bounds. Numerical studies are performed on synthetic data and a dataset of New York City taxi trips.
Immigration, Economic Freedom, and Ideology

ABSTRACTConcerns about immigrants’ impact on US institutions are not new. We find such concerns in the correspondences and writings of Benjamin Franklin, Thomas Jefferson, and Alexander Hamilton. M...
The Affordability of the Individual Markets in the Affordable Care Act: Analyses of Premium Increases and Cost Reductions from an Expanded Cross-Subsidization Perspective

In response to the significant premium increases and the “death spiral” concern, this research examines the stability and affordability of the ACA individual markets by quantifying appropriate prem...
A Wave Model for Dwarf Novae

The rapid coherent oscillation during a dwarf nova outburst is attributed to an accretion-driven wave going around the white dwarf component of the binary system. The increase and decrease in the period of this oscillation is due to the change in the velocity of the wave as it is first being driven and then damped. Qualitatively, a large number of observations can be explained with such a model. The beginnings of a mathematical representation of this model are developed.
Collaborative Privacy for Web Applications

Real-time, online-editing web apps provide free and convenient services for collaboratively editing, sharing and storing files. The benefits of these web applications do not come for free: not only do service providers have full access to the users’ files, but they also control access, transmission, and storage mechanisms for them. As a result, user data may be at risk of data mining, third-party interception, or even manipulation. To combat this, we propose a new system for helping to preserve the privacy of user data within collaborative environments. There are several distinct challenges in producing such a system, including developing an encryption mechanism that does not interfere with the back-end (and often proprietary) control mechanisms utilized by the service, and identifying transparent code hooks through which to obfuscate user data. Toward the first challenge, we develop a character-level encryption scheme that is more resilient to the types of attacks that plague classical substitution ciphers. For the second challenge, we design a browser extension that robustly demonstrates the feasibility of our approach, and show a concrete implementation for Google Chrome and the widely-used Google Docs platform. Our example tangibly demonstrates how several users with a shared key can collaboratively and transparently edit a Google Docs document without revealing the plaintext directly to Google.
Cost effective, experimentally robust differential-expression analysis for human/mammalian, pathogen and dual-species transcriptomics.

As sequencing read length has increased, researchers have quickly adopted longer reads for their experiments. Here, we examine 14 pathogen or host-pathogen differential gene expression data sets to assess whether using longer reads is warranted. A variety of data sets was used to assess what genomic attributes might affect the outcome of differential gene expression analysis including: gene density, operons, gene length, number of introns/exons and intron length. No genome attribute was found to influence the data in principal components analysis, hierarchical clustering with bootstrap support, or regression analyses of pairwise comparisons that were undertaken on the same reads, looking at all combinations of paired and unpaired reads trimmed to 36, 54, 72 and 101 bp. Read pairing had the greatest effect when there was little variation in the samples from different conditions or in their replicates (e.g. little differential gene expression). But overall, 54 and 72 bp reads were typically most similar. Given differences in costs and mapping percentages, we recommend 54 bp reads for organisms with no or few introns and 72 bp reads for all others. In a third of the data sets, read pairing had absolutely no effect, despite paired reads having twice as much data. Therefore, single-end reads seem robust for differential-expression analyses, but in eukaryotes paired-end reads are likely desired to analyse splice variants and should be preferred for data sets that are acquired with the intent to be community resources that might be used in secondary data analyses.
On the Empirical Validity of Cumulative Prospect Theory: Experimental Evidence of Rank‐Independent Probability Weighting

Cumulative Prospect Theory (CPT), the leading behavioral account of decision making under uncertainty, avoids the dominance violations implicit in Prospect Theory (PT) by assuming that the probability weight applied to a given outcome depends on its ranking. We devise a simple and direct non-parametric method for measuring the change in relative probability weights resulting from a change in payoff ranks. We find no evidence that these weights are even modestly sensitive to ranks. Conventional calibrations of CPT preferences imply that the percentage change in probability weights should be an order of magnitude larger than we observe. It follows either that probability weighting is not rank-dependent, or that the weighting function is nearly linear. Non-parametric measurement of the change in relative probability weights resulting from changes in probabilities rules out the second possibility. Additional tests nevertheless indicate that the dominance patterns predicted by PT do not arise. We reconcile these findings by positing a form of complexity aversion that generalizes the well-known certainty effect.
Markets Beyond Nash Welfare for Leontief Utilities.

We study the allocation of divisible goods to competing agents via a market mechanism, focusing on agents with Leontief utilities. The majority of the economics and mechanism design literature has focused on \emph{linear} prices, meaning that the cost of a good is proportional to the quantity purchased. Equilibria for linear prices are known to be exactly the maximum Nash welfare allocations. \emph{Price curves} allow the cost of a good to be any (increasing) function of the quantity purchased. We show that price curve equilibria are not limited to maximum Nash welfare allocations with two main results. First, we show that an allocation can be supported by strictly increasing price curves if and only if it is \emph{group-domination-free}. A similarly characterization holds for weakly increasing price curves. We use this to show that given any allocation, we can compute strictly (or weakly) increasing price curves that support it (or show that none exist) in polynomial time. These results involve a connection to the \emph{agent-order matrix} of an allocation, which may have other applications. Second, we use duality to show that in the bandwidth allocation setting, any allocation maximizing a CES welfare function can be supported by price curves.
Altered NaCl concentration of airway surface liquid in cystic fibrosis.

A novel isotopic technique suggests that the [Na] and [Cl] of airway surface liquid are both normally ~50 mM. In cystic fibrosis, lack of the functional cystic fibrosis transmembrane conductance regulator (CFTR) causes failure of transcellular Cl absorption, resulting in an elevation of [Na] and [Cl] of airway surface liquid to ~100 mM.
Covariate Regularized Community Detection in Sparse Graphs

In this article, we investigate community detection in networks in the presence of node covariates. In many instances, covariates and networks individually only give a partial view of the cluster s...
Cross-border cooperation between securities regulators

Abstract The events of September 11, 2001, prompted sweeping cross-border coordination efforts for securities regulators around the globe. After 9/11, the International Organization of Securities Commissions (IOSCO) forged a nonbinding arrangement—the Multilateral Memorandum of Understanding Concerning Consultation and Cooperation and the Exchange of Information (MMoU)—that standardized the protocol for information sharing among participating securities regulators. Because regulators from different countries entered the MMoU at different times, their enlistments created a set of staggered shocks. I use these shocks to show that the resulting cross-border cooperation (a) increases cross-border enforcement and (b) reduces the cost of liquidity provision in the capital markets of participating countries. These results support the conclusion that the MMoU helps fill gaps in cross-border regulation that historically exposed investors to information asymmetry, agency costs, and expropriation risks.
Hsc70 Ameliorates the Vesicle Recycling Defects Caused by Excess α-Synuclein at Synapses

α-Synuclein overexpression and aggregation are linked to Parkinson's disease (PD), dementia with Lewy bodies (DLB), and several other neurodegenerative disorders. In addition to effects in the cell body, α-synuclein accumulation occurs at presynapses where the protein is normally localized. While it is generally agreed that excess α-synuclein impairs synaptic vesicle trafficking, the underlying mechanisms are unknown. We show here that acute introduction of excess human α-synuclein at a classic vertebrate synapse, the lamprey reticulospinal (RS) synapse, selectively impaired the uncoating of clathrin-coated vesicles (CCVs) during synaptic vesicle recycling, leading to an increase in endocytic intermediates and a severe depletion of synaptic vesicles. Furthermore, human α-synuclein and lamprey γ-synuclein both interact in vitro with Hsc70, the chaperone protein that uncoats CCVs at synapses. After introducing excess α-synuclein, Hsc70 availability was reduced at stimulated synapses, suggesting Hsc70 sequestration as a possible mechanism underlying the synaptic vesicle trafficking defects. In support of this hypothesis, increasing the levels of exogenous Hsc70 along with α-synuclein ameliorated the CCV uncoating and vesicle recycling defects. These experiments identify a reduction in Hsc70 availability at synapses, and consequently its function, as the mechanism by which α-synuclein induces synaptic vesicle recycling defects. To our knowledge, this is the first report of a viable chaperone-based strategy for reversing the synaptic vesicle trafficking defects associated with excess α-synuclein, which may be of value for improving synaptic function in PD and other synuclein-linked diseases.
Theory In, Theory Out: The Uses of Social Theory in Machine Learning for Social Science

Research at the intersection of machine learning and the social sciences has provided critical new insights into social behavior. At the same time, a variety of issues have been identified with the machine learning models used to analyze social data. These issues range from technical problems with the data used and features constructed, to problematic modeling assumptions, to limited interpretability, to the models' contributions to bias and inequality. Computational researchers have sought out technical solutions to these problems. The primary contribution of the present work is to argue that there is a limit to these technical solutions. At this limit, we must instead turn to social theory. We show how social theory can be used to answer basic methodological and interpretive questions that technical solutions cannot when building machine learning models, and when assessing, comparing, and using those models. In both cases, we draw on related existing critiques, provide examples of how social theory has already been used constructively in existing work, and discuss where other existing work may have benefited from the use of specific social theories. We believe this paper can act as a guide for computer and social scientists alike to navigate the substantive questions involved in applying the tools of machine learning to social data.
Fast and Agile Vision-Based Flight with Teleoperation and Collision Avoidance on a Multirotor

We present a multirotor architecture capable of aggressive autonomous flight and collision-free teleoperation in unstructured, GPS-denied environments. The proposed system enables aggressive and safe autonomous flight around clutter by integrating recent advancements in visual-inertial state estimation and teleoperation. Our teleoperation framework maps user inputs onto smooth and dynamically feasible motion primitives. Collision-free trajectories are ensured by querying a locally consistent map that is incrementally constructed from forward-facing depth observations. Our system enables a non-expert operator to safely navigate a multirotor around obstacles at speeds of 10 m/s. We achieve autonomous flights at speeds exceeding 12 m/s and accelerations exceeding 12 m/s\(^2\) in a series of outdoor field experiments that validate our approach.
Positivity of Divisor Classes on the Strata of Differentials

Three decades ago Cornalba-Harris proved a fundamental positivity result for divisor classes associated to families of stable curves. In this paper we establish an analogous positivity result for divisor classes associated to families of stable differentials.
Measurements of elastoresistance under pressure by combining in-situ tunable quasi-uniaxial stress with hydrostatic pressure.

Uniaxial stress, as well as hydrostatic pressure are often used to tune material properties in condensed matter physics. Here, we present a setup that allows for the study of the combined effects of quasi-uniaxial stress and hydrostatic pressure. Following earlier designs for measurements under finite stress at ambient pressures [e.g., Chu et al., Science 337, 710 (2012)], the present setup utilizes a piezoelectric actuator to change stress in situ inside the piston–cylinder pressure cell. We show that the actuator can be operated over the full temperature (from 30 K up to 260 K) and pressure range (up to ≈2 GPa), resulting in a clear and measurable quasi-uniaxial strain. To demonstrate functionality, measurements of the elastoresistance (i.e., the change of resistance of a sample as a response to quasi-uniaxial strain) under finite hydrostatic pressure on the iron-based compound BaFe2As2 are presented as a proof-of-principle example and discussed in the framework of electronic nematicity. Overall, this work introduces the combination of in situ tunable quasi-uniaxial stress and large (up to ≈2 GPa) hydrostatic pressure as a powerful combination in the study of novel electronic phases. In addition, it also points toward further technical advancements which can be made in the future.Uniaxial stress, as well as hydrostatic pressure are often used to tune material properties in condensed matter physics. Here, we present a setup that allows for the study of the combined effects of quasi-uniaxial stress and hydrostatic pressure. Following earlier designs for measurements under finite stress at ambient pressures [e.g., Chu et al., Science 337, 710 (2012)], the present setup utilizes a piezoelectric actuator to change stress in situ inside the piston–cylinder pressure cell. We show that the actuator can be operated over the full temperature (from 30 K up to 260 K) and pressure range (up to ≈2 GPa), resulting in a clear and measurable quasi-uniaxial strain. To demonstrate functionality, measurements of the elastoresistance (i.e., the change of resistance of a sample as a response to quasi-uniaxial strain) under finite hydrostatic pressure on the iron-based compound BaFe2As2 are presented as a proof-of-principle example and discussed in the framework of electronic nematicity. Overall, this w...
Hat1-Dependent Lysine Acetylation Targets Diverse Cellular Functions

Lysine acetylation has emerged as one of the most important post-translational modifications, regulating different biological processes. However, its regulation by lysine acetyltransferases is still unclear in most cases. Hat1 is a lysine acetyltransferase originally identified based on its ability to acetylate histones. Using an unbiased proteomics approach, we have determined how loss of Hat1 affects the mammalian acetylome. Hat1+/+ and Hat1-/- mouse embryonic fibroblast cell lines were grown in both glucose- and galactose-containing media, as Hat1 is required for growth on galactose, and Hat1-/- cells exhibit defects in mitochondrial function. Following trypsin digestion of whole cell extracts, acetylated peptides were enriched by acetyllysine affinity purification, and acetylated peptides were identified and analyzed by label-free quantitation. Comparison of the acetylome from Hat1+/+ cells grown on galactose and glucose demonstrated that there are large carbon source-dependent changes in the mammalian acetylome where the acetylation of enzymes involved in glycolysis were the most affected. Comparisons of the acetylomes from Hat1+/+ and Hat1-/- cells identified 65 proteins whose acetylation decreased by at least 2.5-fold in cells lacking Hat1. In Hat1-/- cells, acetylation of the autoregulatory loop of CBP (CREB-binding protein) was the most highly affected, decreasing by up to 20-fold. In addition to the proteins involved in chromatin structure, Hat1-dependent acetylation was also found in a number of transcriptional regulators, including p53 and mitochondrial proteins. Hat1 mitochondrial localization suggests that it may be directly involved in the acetylation of mitochondrial proteins. Data are available via ProteomeXchange with identifier PXD017362.
Uniting Top-Down and Bottom-Up Strategies Using Fabricated Nanostructures as Hosts for Synthesis of Nanomites

Gold nanomites on gold nanotriangles were produced using a combination of bottom-up synthesis and top-down fabrication. Modified gold nanostar protocols were the basis for the synthesis to form the...
Identifying Severe Stroke Patients Likely to Benefit From Thrombectomy Despite Delays of up to a Day

Selected patients with large vessel occlusions (LVO) can benefit from thrombectomy up to 24 hours after onset. Identifying patients who might benefit from late intervention after transfer from community hospitals to thrombectomy-capable centers would be valuable. We searched for presentation biomarkers to identify such patients. Frequent MR imaging over 2 days of 38 untreated LVO patients revealed logarithmic growth of the ischemic infarct core. In 24 patients with terminal internal carotid artery or the proximal middle cerebral artery occlusions we found that an infarct core growth rate (IGR) 89% for identifying patients who would still have a core of <50 ml 24 hours after stroke onset, a core size that should predict favorable outcomes with thrombectomy. Published reports indicate that up to half of all LVO stroke patients have an IGR <4.1 ml/hr. Other potentially useful biomarkers include the NIHSS and the perfusion measurements MTT and Tmax. We conclude that many LVO patients have a stroke physiology that is favorable for late intervention, and that there are biomarkers that can accurately identify them at early time points as suitable for transfer for intervention.
Racial Differences in Pain and Function Following Knee Arthroplasty: A Secondary Analysis From a Multicenter Randomized Clinical Trial.

Objective The assessment of racial differences in pain and function outcome following knee arthroplasty (KA) has received little attention despite very substantial literature exploring a variety of other prognostic factors. The present study was undertaken to determine whether race was associated with KA outcome after accounting for potential confounding factors. Methods We conducted a secondary analysis of a randomized clinical trial of 384 participants with moderate-to-high pain catastrophizing who underwent KA. Preoperative measures included race/ethnicity status as well as a variety of potential confounders, including socioeconomic status, comorbidity, and bodily pain. Outcome measures were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scales as well as performance measures. Linear mixed-effects models compared outcomes over a 1-year follow-up period for African American versus non-African American participants. Results WOMAC pain scores differences for African American versus non-African American participants averaged ~2 points in unadjusted analyses and 1-1.5 points in adjusted analyses. In adjusted analyses, follow-up WOMAC function scores differed by 6 points for African Americans compared to non-African Americans (P = 0.002). Conclusion African Americans generally had worse pain, function, and performance prior to KA and worse scores after surgery, but differences were small and attenuated by ~25-50% after adjustment for potential confounding. Only WOMAC function scores showed clinically important postsurgical differences in adjusted analyses. Clinicians should be aware that after adjustment for potential confounders, African Americans have approximately equivalent outcomes compared to others, with the exception of WOMAC function score.
The Case for Colonialism

AbstractWITHDRAWAL NOTICEThis Viewpoint essay has been withdrawn at the request of the academic journal editor, and in agreement with the author of the essay. Following a number of complaints, Taylor & Francis conducted a thorough investigation into the peer review process on this article. Whilst this clearly demonstrated the essay had undergone double-blind peer review, in line with the journal's editorial policy, the journal editor has subsequently received serious and credible threats of personal violence. These threats are linked to the publication of this essay. As the publisher, we must take this seriously. Taylor & Francis has a strong and supportive duty of care to all our academic editorial teams, and this is why we are withdrawing this essay.
Deep Model Reference Adaptive Control

We present a new neuroadaptive architecture: Deep Neural Network based Model Reference Adaptive Control (DMRAC). Our architecture utilizes the power of deep neural network representations for modeling significant nonlinearities while marrying it with the boundedness guarantees that characterize MRAC based controllers. We demonstrate through simulations and analysis that DMRAC can subsume previously studied learning based MRAC methods, such as concurrent learning and GP-MRAC. This makes DMRAC a highly powerful architecture for high-performance control of nonlinear systems with long-term learning properties.
Conservative liberalism: Hume, Smith, and Burke as policy liberals and polity conservatives

Abstract On regular issues of policy reform—presupposing a stable integrated polity— Hume, Smith, and Burke were liberal in the original political meaning of “liberal.” Thus, on policy reform, although they accorded the status quo a certain presumption (as any reasonable person must), the more distinctive feature is that they maintained (even propounded, most plainly in Smith's case) a presumption of liberty in matters of policy reform. But we need another conceptualization that treats their attitudes about establishing, reforming, and securing the wider structure of political institutions, political procedure, and political culture and character—matters of polity reformation. On polity reformation, they showed sensibilities for which “conservative” is apt (though such conservatism was not otherwise purely neutral). Hume, Smith, and Burke were basically in agreement in the matters treated here. They are polity conservatives. The article develops the two conceptualizations—policy reform and polity reformation—, an understanding of “liberal” applicable to policy reform, and an understanding of “conservative” (namely, a heavy presumption of the status quo) that may be applied to policy reform and to polity reformation. If we code the three thinkers as PLPC (policy liberals and polity conservatives), we may put the matter this way: It would be meaningful but wrong to code them instead PCPC (policy conservatives and polity conservatives). I call their outlook conservative liberalism. I deal disproportionately with Burke, to tussle with two sets of imagined interlocutors, one on Burke as liberal, and the other on Burkean insight on polity reformation.
Inducing Uniform Asymptotic Stability in Non-Autonomous Accelerated Optimization Dynamics via Hybrid Regularization

There have been many recent efforts to study accelerated optimization algorithms from the perspective of dynamical systems. In this paper, we focus on the robustness properties of the time-varying continuous-time version of these dynamics. These properties are critical for the implementation of accelerated algorithms in feedback-based control and optimization architectures. We show that a family of dynamics related to the continuous-time limit of Nesterov’s accelerated gradient method can be rendered unstable under arbitrarily small bounded disturbances. Indeed, while solutions of these dynamics may converge to the set of optimizers, in general, this set may not be uniformly asymptotically stable. To induce uniformity, and robustness as a byproduct, we propose a framework where the dynamics are regularized by using resetting mechanisms that are modeled by well-posed hybrid dynamical systems. For these hybrid dynamics, we establish uniform asymptotic stability and robustness properties, as well as convergence rates that are similar to those of the non-hybrid dynamics. We finish by characterizing a family of discretization mechanisms that retain the main stability and robustness properties of the hybrid algorithms.
Multilinear Oscillatory Integral Operators and Geometric Stability

In this article we prove a sharp decay estimate for certain multilinear oscillatory integral operators of a form inspired by the general framework of Christ et al. (Duke Math 130(2):321–351, 2005). A key purpose of this work is to determine when such estimates are stable under smooth perturbations of both the phase and corresponding projections, which are typically only assumed to be linear. The proof is accomplished by a novel decomposition which mixes features of Gabor or windowed Fourier bases with features of wavelet or Littlewood–Paley decompositions. This decomposition very nearly diagonalizes the problem and seems likely to have useful applications to other geometrically-inspired objects in Fourier analysis.
Heterologous caffeic acid biosynthesis in Escherichia coli is affected by choice of tyrosine ammonia lyase and redox partners for bacterial Cytochrome P450.

Caffeic acid is industrially recognized for its antioxidant activity and therefore its potential to be used as an anti-inflammatory, anticancer, antiviral, antidiabetic and antidepressive agent. It is traditionally isolated from lignified plant material under energy-intensive and harsh chemical extraction conditions. However, over the last decade bottom-up biosynthesis approaches in microbial cell factories have been established, that have the potential to allow for a more tailored and sustainable production. One of these approaches has been implemented in Escherichia coli and only requires a two-step conversion of supplemented l-tyrosine by the actions of a tyrosine ammonia lyase and a bacterial Cytochrome P450 monooxygenase. Although the feeding of intermediates demonstrated the great potential of this combination of heterologous enzymes compared to others, no de novo synthesis of caffeic acid from glucose has been achieved utilizing the bacterial Cytochrome P450 thus far. The herein described work aimed at improving the efficiency of this two-step conversion in order to establish de novo caffeic acid formation from glucose. We implemented alternative tyrosine ammonia lyases that were reported to display superior substrate binding affinity and selectivity, and increased the efficiency of the Cytochrome P450 by altering the electron-donating redox system. With this strategy we were able to achieve final titers of more than 300 µM or 47 mg/L caffeic acid over 96 h in an otherwise wild type E. coli MG1655(DE3) strain with glucose as the only carbon source. We observed that the choice and gene dose of the redox system strongly influenced the Cytochrome P450 catalysis. In addition, we were successful in applying a tethering strategy that rendered even a virtually unproductive Cytochrome P450/redox system combination productive. The caffeic acid titer achieved in this study is about 10% higher than titers reported for other heterologous caffeic acid pathways in wildtype E. coli without l-tyrosine supplementation. The tethering strategy applied to the Cytochrome P450 appears to be particularly useful for non-natural Cytochrome P450/redox partner combinations and could be useful for other recombinant pathways utilizing bacterial Cytochromes P450.
High-Throughput Cryo-EM Enabled by User-Free Preprocessing Routines

Single-particle cryoelectron microscopy (cryo-EM) continues to grow into a mainstream structural biology technique. Recent developments in data collection strategies alongside new sample preparation devices herald a future where users will collect multiple datasets per microscope session. To make cryo-EM data processing more automatic and user-friendly, we have developed an automatic pipeline for cryo-EM data preprocessing and assessment using a combination of deep-learning and image-analysis tools. We have verified the performance of this pipeline on a number of datasets and extended its scope to include sample screening by the user-free assessment of the qualities of a series of datasets under different conditions. We propose that our workflow provides a decision-free solution for cryo-EM, making data preprocessing more generalized and robust in the high-throughput era as well as more convenient for users from a range of backgrounds.
Angiotensin‐(1‐7) Improves Integrated Cardiometabolic Function in Aged Mice

Angiotensin (Ang)-(1-7) is a beneficial renin-angiotensin system (RAS) hormone that elicits protective cardiometabolic effects in young animal models of hypertension, obesity, and metabolic syndrome. The impact of Ang-(1-7) on cardiovascular and metabolic outcomes during aging, however, remains unexplored. This study tested the hypothesis that Ang-(1-7) attenuates age-related elevations in blood pressure and insulin resistance in mice. Young adult (two-month-old) and aged (16-month-old) male C57BL/6J mice received Ang-(1-7) (400 ng/kg/min) or saline for six-weeks via a subcutaneous osmotic mini-pump. Arterial blood pressure and metabolic function indices (body composition, insulin sensitivity, and glucose tolerance) were measured at the end of treatment. Adipose and cardiac tissue masses and cardiac RAS, sympathetic and inflammatory marker gene expression were also measured. We found that chronic Ang-(1-7) treatment decreased systolic and mean blood pressure, with a similar trend for diastolic blood pressure. Ang-(1-7) also improved insulin sensitivity in aged mice to levels in young mice, without effects on glucose tolerance or body composition. The blood pressure-lowering effects of Ang-(1-7) in aged mice were associated with reduced sympathetic outflow to the heart. These findings suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic risk.
A NEW MEASURE OF FOREIGN RULE BASED ON GENETIC DISTANCE

The consequences for countries of past foreign rule are the subject of a vast literature across history and the social sciences. This paper constructs a novel measure of past foreign (or minority) rule - the genetic distance of a country’s ruling elite in the year 1900 from the country’s ethnic majority - by mapping historical information on these groups to existing data on bilateral genetic distances between countries and populations. This generates an “elite-population genetic distance” in 1900 (EPGD_1900) for each of 228 present-day countries and territories. While this continuous measure is positively correlated with existing dichotomous measures of foreign rule, it captures an additional dimension of variation absent from the existing measures. The paper documents robust conditional correlations between EPGD_1900 and current income levels, and between EPGD_1900 and current fiscal capacity (controlling for various relevant country characteristics, existing measures of foreign rule, the genetic distance of a country’s ethnic majority from that of the UK, and continent fixed effects). In particular, both current GDP per capita and tax revenue as a percentage of GDP are substantially lower for countries and territories with higher EPGD_1900. While these relationships may be attributable to unobserved and persistent variation in state-building capabilities across societies, the results are robust to controlling for a widely-used index of state antiquity that measures the history of state-building capacity.