cssi/SciSciGPT-SciSciNet huggingface dataset:
Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging

Fluorogenic probes, small-molecule sensors that unmask brilliant fluorescence upon exposure to specific stimuli, are powerful tools for chemical biology. Those probes that respond to enzymatic catalysis illuminate the complex dynamics of biological processes at a level of spatiotemporal detail and sensitivity unmatched by other techniques. Here, we review recent advances in enzyme-activated fluorogenic probes for biological imaging. We organize our survey by enzyme classification, with emphasis on fluorophore masking strategies, modes of enzymatic activation, and the breadth of current and future applications. Key challenges such as probe selectivity and spectroscopic requirements are described alongside therapeutic, diagnostic, and theranostic opportunities.
Towards Accountable AI: Hybrid Human-Machine Analyses for Characterizing System Failure

As machine learning systems move from computer-science laboratories into the open world, their accountability becomes a high priority problem. Accountability requires deep understanding of system behavior and its failures. Current evaluation methods such as single-score error metrics and confusion matrices provide aggregate views of system performance that hide important shortcomings. Understanding details about failures is important for identifying pathways for refinement, communicating the reliability of systems in different settings, and for specifying appropriate human oversight and engagement. Characterization of failures and shortcomings is particularly complex for systems composed of multiple machine learned components. For such systems, existing evaluation methods have limited expressiveness in describing and explaining the relationship among input content, the internal states of system components, and final output quality. We present Pandora, a set of hybrid human-machine methods and tools for describing and explaining system failures. Pandora leverages both human and system-generated observations to summarize conditions of system malfunction with respect to the input content and system architecture. We share results of a case study with a machine learning pipeline for image captioning that show how detailed performance views can be beneficial for analysis and debugging.
Colored range closest-pair problem under general distance functions

The range closest-pair (RCP) problem is the range-search version of the classical closest-pair problem, which aims to store a given dataset of points in some data structure such that when a query range X is specified, the closest pair of points contained in X can be reported efficiently. A natural generalization of the RCP problem is the colored range closest-pair (CRCP) problem in which the given data points are colored and the goal is to find the closest bichromatic pair contained in the query range. All the previous work on the RCP problem was restricted to the uncolored version and the Euclidean distance function. In this paper, we make the first progress on the CRCP problem. We investigate the problem under a general distance function induced by a monotone norm; in particular, this covers all the Lp-metrics for p ≥ 1 and the L∞-metric. We design efficient (1+e)-approximate CRCP data structures for orthogonal queries in R2, where e > 0 is a pre-specified parameter. The highlights are two data structures for answering rectangle queries, one of which uses O(e−1n log4n) space and O(log4n + e−1 log3n + e−2 log n) query time while the other uses O(e−1n log3n) space and O(log5n + e−1 log4n + e−2 log2n) query time, where n is the size of the input dataset. In addition, we also apply our techniques to the CRCP problem in higher dimensions, obtaining efficient data structures for slab, 2-box, and 3D dominance queries. Before this paper, almost all the existing results for the RCP problem were achieved in R2.
Approximations of Schatten Norms via Taylor Expansions

In many applications of data science and machine learning data is represented by large matrices. Fast and accurate analysis of such matrices is a challenging task that is of paramount importance for the aforementioned applications. Randomized numerical linear algebra (RNLA) is an popular area of research that often provides such fast and accurate algorithmic methods for massive matrix computations. Many critical problems in RNLA boil down to approximating spectral functions and one of the most fundamental examples of such spectral functions is Schatten p norm. The p-th Schatten norm for matrix \(A \in R^{n_1\times n_2}\) is defined as the \(l_p\) norm of a vector comprised of singular values of matrix A, i.e., $$ \Vert A\Vert _{p} = \left( \sum _{i=1}^{\min {(n_1,n_2)}} |\sigma _i(A)|^{p}\right) ^{1/{p}}, $$ where \(\sigma _i(A)\) is the i-th singular value of A.
Designing adaptive neural networks for energy-constrained image classification

As convolutional neural networks (CNNs) enable state-of-the-art computer vision applications, their high energy consumption has emerged as a key impediment to their deployment on embedded and mobile devices. Towards efficient image classification under hardware constraints, prior work has proposed adaptive CNNs, i.e., systems of networks with different accuracy and computation characteristics, where a selection scheme adaptively selects the network to be evaluated for each input image. While previous efforts have investigated different network selection schemes, we find that they do not necessarily result in energy savings when deployed on mobile systems. The key limitation of existing methods is that they learn only how data should be processed among the CNNs and not the network architectures, with each network being treated as a blackbox. To address this limitation, we pursue a more powerful design paradigm where the architecture settings of the CNNs are treated as hyper-parameters to be globally optimized. We cast the design of adaptive CNNs as a hyper-parameter optimization problem with respect to energy, accuracy, and communication constraints imposed by the mobile device. To efficiently solve this problem, we adapt Bayesian optimization to the properties of the design space, reaching near-optimal configurations in few tens of function evaluations. Our method reduces the energy consumed for image classification on a mobile device by up to 6×, compared to the best previously published work that uses CNNs as blackboxes. Finally, we evaluate two image classification practices, i.e., classifying all images locally versus over the cloud under energy and communication constraints.
Spectrum Measurement Markets for Tiered Spectrum Access

The recent framework for tiered spectrum sharing in the 3.5 GHz band establishes rules in which multiple firms called Environment Sensing Capability operators (ESCs) may measure spectrum occupancy and sell these measurements to other firms to help facilitate spectrum access. Motived by this we consider a scenario in which two spectrum access firms (SAs) seeks to access a shared band of spectrum and must in turn purchase spectrum measurements from one of two ESCs. Given the measurements they purchase, the SA firms then compete on price to serve customers in a shared band of spectrum. We study how differences in the quality and price of the spectrum measurements impact the resulting market equilibrium between the SAs and find that having different qualities of measurements available to different SAs can lead to better economic welfare.
Robots Racialized in the Likeness of Marginalized Social Identities are Subject to Greater Dehumanization than those racialized as White

The emergence and spread of humanlike robots into increasingly public domains has revealed a concerning phenomenon: people's unabashed dehumanization of robots, particularly those gendered as female. Here we examined this phenomenon further towards understanding whether other socially marginalized cues (racialization in the likeness of Asian and Black identities), like female-gendering, are associated with the manifestation of dehumanization (e.g., objectification, stereotyping) in human-robot interactions. To that end, we analyzed free-form comments (N = 535) on three videos, each depicting a gynoid - Bina48, Nadine, or Yangyang - racialized as Black, White, and Asian respectively. As a preliminary control, we additionally analyzed commentary (N = 674) on three videos depicting women embodying similar identity cues. The analyses indicate that people more frequently dehumanize robots racialized as Asian and Black, than they do of robots racialized as White. Additional, preliminary evaluation of how people's responding towards the gynoids compares to that towards other people suggests that the gynoids' ontology (as robots) further facilitates the dehumanization.
Theory, research design assumptions, and causal inferences

Abstract Ferri, Zheng, and Zou test Fischer and Verrecchia's (2000) prediction that a reduction in investors’ uncertainty about managers’ financial reporting objectives leads to an increase in the valuation-relevance of earnings reports. They use mandatory CD&A disclosures as an arguably exogenous “shock” that provided investors with more precise information about managers’ contractual incentives and find that these enhanced disclosures increased the relation between firms’ unexpected earnings and stock returns. Using Ferri et al. as a backdrop, we discuss the implicit assumptions invoked in natural experimental research designs and the fundamental role of theory in drawing causal inferences from empirical evidence.
Registration-Based Encryption: Removing Private-Key Generator from IBE

In this work, we introduce the notion of registration-based encryption (RBE for short) with the goal of removing the trust parties need to place in the private-key generator in an IBE scheme. In an RBE scheme, users sample their own public and secret keys. There will also be a “key curator” whose job is only to aggregate the public keys of all the registered users and update the “short” public parameter whenever a new user joins the system. Encryption can still be performed to a particular recipient using the recipient’s identity and any public parameters released subsequent to the recipient’s registration. Decryption requires some auxiliary information connecting users’ public (and secret) keys to the public parameters. Because of this, as the public parameters get updated, a decryptor may need to obtain “a few” additional auxiliary information for decryption. More formally, if n is the total number of identities and \(\mathrm {\kappa }\) is the security parameter, we require the following.
An Issue in the Martingale Analysis of the Influence Maximization Algorithm IMM.

This paper explains a subtle issue in the martingale analysis of the IMM algorithm, a state-of-the-art influence maximization algorithm. Two workarounds are proposed to fix the issue, both requiring minor changes on the algorithm and incurring a slight penalty on the running time of the algorithm.
Multi-Source Domain Adaptation with Mixture of Experts

We propose a mixture-of-experts approach for unsupervised domain adaptation from multiple sources. The key idea is to explicitly capture the relationship between a target example and different source domains. This relationship, expressed by a point-to-set metric, determines how to combine predictors trained on various domains. The metric is learned in an unsupervised fashion using meta-training. Experimental results on sentiment analysis and part-of-speech tagging demonstrate that our approach consistently outperforms multiple baselines and can robustly handle negative transfer.
Coxiella burnetii Blocks Intracellular Interleukin-17 Signaling in Macrophages.

ABSTRACT Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever. Successful host cell infection requires the Coxiella type IVB secretion system (T4BSS), which translocates bacterial effector proteins across the vacuole membrane into the host cytoplasm, where they manipulate a variety of cell processes. To identify host cell targets of Coxiella T4BSS effector proteins, we determined the transcriptome of murine alveolar macrophages infected with a Coxiella T4BSS effector mutant. We identified a set of inflammatory genes that are significantly upregulated in T4BSS mutant-infected cells compared to mock-infected cells or cells infected with wild-type (WT) bacteria, suggesting that Coxiella T4BSS effector proteins downregulate the expression of these genes. In addition, the interleukin-17 (IL-17) signaling pathway was identified as one of the top pathways affected by the bacteria. While previous studies demonstrated that IL-17 plays a protective role against several pathogens, the role of IL-17 during Coxiella infection is unknown. We found that IL-17 kills intracellular Coxiella in a dose-dependent manner, with the T4BSS mutant exhibiting significantly more sensitivity to IL-17 than WT bacteria. In addition, quantitative PCR confirmed the increased expression of IL-17 downstream signaling genes in T4BSS mutant-infected cells compared to WT- or mock-infected cells, including the proinflammatory cytokine genes Il1a, Il1b, and Tnfa, the chemokine genes Cxcl2 and Ccl5, and the antimicrobial protein gene Lcn2. We further confirmed that the Coxiella T4BSS downregulates macrophage CXCL2/macrophage inflammatory protein 2 and CCL5/RANTES protein levels following IL-17 stimulation. Together, these data suggest that Coxiella downregulates IL-17 signaling in a T4BSS-dependent manner in order to escape the macrophage immune response.
Solutions to Axion Electrodynamics in Various Geometries

Recently there has been a surge of new experimental proposals to search for ultralight axion dark matter with axion mass, ${m}_{a}\ensuremath{\lesssim}1\text{ }\text{ }\ensuremath{\mu}\mathrm{eV}$. Many of these proposals search for small oscillating magnetic fields induced in or around a large static magnetic field. Lately, there has been interest in alternate detection schemes which search for oscillating electric fields in a similar setup. In this paper, we explicitly solve Maxwell's equations in a simplified geometry and demonstrate that in this mass range, the axion-induced electric fields are heavily suppressed by boundary conditions. Unfortunately, experimentally measuring axion-induced electric fields is not feasible in this mass regime using the currently proposed setups with static primary fields. We show that at larger axion masses, induced electric fields are not suppressed, but boundary effects may still be relevant for an experiment's sensitivity. We then make a general argument about a generic detector configuration with a static magnetic field to show that the electric fields are always suppressed in the limit of large wavelength.
Perverse Incentives and Safe Harbors in the Endangered Species Act: Evidence From Timber Harvests Near Woodpeckers

Abstract The Endangered Species Act creates perverse incentives for private landowners to destroy potential habitat in order to prevent endangered species from moving onto their properties. Federal agencies recognize these incentives and have tried to counter them with safe-harbor programs that allow landowners to voluntarily provide conservation in exchange for more regulatory certainty. Congress and agencies are both interested in shifting enforcement of the ESA toward this type of voluntary conservation, but there is little evidence of the effectiveness of these programs. This paper uses parcel-level data from federal agencies to provide the first empirical estimates of the effectiveness of a federal safe-harbor program. I find evidence that the program successfully decreases timber harvest behavior that appears to be targeting potential habitat. Based on estimates from both triple-difference and matching models, participation in the safe-harbor program is associated with a 7 to 13 percentage point decrease in harvest activity. The safe-harbor program holds promise to conserve imperiled wildlife while allowing landowners' greater flexibility to maintain traditional land uses.
Rigorous Results for the Distribution of Money on Connected Graphs (Models with Debts)

In this paper, we continue our analysis of spatial versions of agent-based models for the dynamics of money that have been introduced in the statistical physics literature, focusing on two models with debts. Both models consist of systems of economical agents located on a finite connected graph representing a social network. Each agent is characterized by the number of coins she has, which can be negative in case she is in debt, and each monetary transaction consists in one coin moving from one agent to one of her neighbors. In the first model, that we name the model with individual debt limit, the agents are allowed to individually borrow up to a fixed number of coins. In the second model, that we name the model with collective debt limit, agents can borrow coins from a central bank as long as the bank is not empty, with reimbursements occurring each time an agent in debt receives a coin. Based on numerical simulations of the models on complete graphs, it was conjectured that, in the large population/temperature limits, the distribution of money converges to a shifted exponential distribution for the model with individual debt limit, and to an asymmetric Laplace distribution for the model with collective debt limit. In this paper, we prove exact formulas for the distribution of money that are valid for all possible social networks. Taking the large population/temperature limits in the formula found for the model with individual debt limit, we prove convergence to the shifted exponential distribution, thus establishing the first conjecture. Simplifying the formula found for the model with collective debt limit is more complicated, but using a computer to plot this formula shows an almost perfect fit with the Laplace distribution, which strongly supports the second conjecture.
Reducing Bias in Estimates for the Law of Crime Concentration

The law of crime concentration states that half of the cumulative crime in a city will occur within approximately 4% of the city’s geography. The law is demonstrated by counting the number of incidents in each of N spatial areas (street segments or grid cells) and then computing a parameter based on the counts, such as a point estimate on the Lorenz curve or the Gini index. Here we show that estimators commonly used in the literature for these statistics are biased when the number of incidents is low (several thousand or less). Our objective is to significantly reduce bias in estimators for the law of crime concentration. By modeling crime counts as a negative binomial, we show how to compute an improved estimate of the law of crime concentration at low event counts that significantly reduces bias. In particular, we use the Poisson–Gamma representation of the negative binomial and compute the concentration statistic via integrals for the Lorenz curve and Gini index of the inferred continuous Gamma distribution. We illustrate the Poisson–Gamma method with synthetic data along with homicide data from Chicago. We show that our estimator significantly reduces bias and is able to recover the true law of crime concentration with only several hundred events. The Poisson–Gamma method has applications to measuring the concentration of rare events, comparisons of concentration across cities of different sizes, and improving time series estimates of crime concentration.
The association of urinary phosphorous-containing flame retardant metabolites and self-reported personal care and household product use among couples seeking fertility treatment

Phosphorous-containing flame-retardants (PFRs) are widely detected. They are used both as a flame retardant as well as plasticizer. A subset of 230 women and 229 men were recruited from Massachusetts General Hospital fertility clinic between 2005 and 2015. At each visit, participants completed a questionnaire of personal care product (PCP) and household product (HP) use. Metabolites [bis(1,3-dichloro-2-propyl) phosphate, diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate and bis(1-chloro-2-propyl) phosphate] were measured in urine (1–5 samples; n = 638 women, n = 335 men). Associations were assessed using generalized mixed models, adjusted for SG, age, BMI, smoking, education, and season. In women, moisturizer (60%), nail polish remover (77%), and nail polish (134%) use were associated (p < 0.05) with an increase in DPHP concentrations, while ip-PPP concentrations increased 21–27% with conditioner, cosmetics, deodorant, and hair product use. Mouthwash and vinyl glove use were associated with a respective 31% and 92% increase in DPHP among men. Our exploratory analysis suggests PFRs may be used as a plasticizer in consumer products, and nail polish use contributes to internal DPHP exposure. Further research is needed to understand how PFRs are used in these products and how it relates to exposure.
Tolerance and Compromise in Social Networks

Individuals typically differ in their identities—the behaviors they deem ideal for themselves and for the members of their network—and in their tolerance for behaviors that deviate from their ideal...
Gendered norms for family size, employment, and occupation: Are there personal costs for violating them?

The present study investigated gendered stereotypes involving women’s family size, employment, and occupation. Eleven ratings of targets’ social and personality characteristics were ascribed by 400 undergraduates to a hypothetical married woman described as voluntarily childfree or the mother of one, two, or eight children, and as nonemployed or employed either part or full time in either a gender-appropriate or gender-inappropriate occupation. Women employed in gender-atypical occupations were considered less expressive and were socially distanced, but this factor did not interact with family size. Two-children mothers were regarded favorably as was employment. Prior findings denigrating single-child mothers and glorifying eight-children mothers were not replicated—both groups were rated similar to normative, two-children mothers. Consistent with prior research, childfree women were evaluated least favorably. Findings suggest that norms regarding both family size (two children) and employment exist among contemporary college students.
Minimum Variance Unbiased (MVU) Estimator

Determining the minimum variance of an unbiased estimator constitutes a fundamental topic in mathematical statistics. Two primary results are the Cramer–Rao inequality, which gives a lower bound on the variance of an unbiased estimator, and the Rao–Blackwell theorem, which supplies a method for improving the variance of unbiased estimators that are not functions of sufficient statistics. The strongest results are available for sufficient statistics from complete exponential families. However, any functions of sufficient statistics will attain the Cramer–Rao lower bound for sufficiently large sample sizes. Keywords: Cramer–Rao lower bound; information inequality; Rao–Blackwell theorem; maximum likelihood; exponential family sufficient statistics; completeness
Consider the human work experience when integrating robotics in the workplace

Worldwide, manufacturers are reimagining the future of their workforce and its connection to technology. Rather than replacing humans, Industry 5.0 explores how humans and robots can best complement one another's unique strengths. However, realizing this vision requires an in-depth understanding of how workers view the positive and negative attributes of their jobs, and the place of robots within it. In this paper, we explore the relationship between work attributes and automation goals by engaging in field research at a manufacturing plant. We conducted 50 face-to-face interviews with assembly-line workers $(\mathrm{n}=50)$ , which we analyzed using discourse analysis and social constructivist methods. We found that the work attributes deemed most positive by participants include social interaction, movement and exercise, (human) autonomy, problem solving, task variety, and building with their hands. The main negative work attributes included health and safety issues, feeling rushed, and repetitive work. We identified several ways robots could help reduce negative work attributes and enhance positive ones, such as reducing work interruptions and cultivating physical and psychological well-being. Based on our findings, we created a set of integration considerations for organizations planning to deploy robotics technology, and discuss how the manufacturing and HRI communities can explore these ideas in the future.
Financial Inclusion, Human Capital, and Wealth Accumulation: Evidence from the Freedman’s Savings Bank

This paper studies how access to financial services among a previously unbanked group affects human capital, labor market, and wealth outcomes. We use novel data from the Freedman’s Savings Bank—created following the American Civil War to serve free Blacks—employing an instrumental variables strategy exploiting the staggered rollout of bank branches. Families with accounts are more likely to have children in school, be literate, work, and have higher occupational income, business ownership and real estate wealth. Placebo effects are not present using planned but unbuilt branches, or for Whites, suggesting significant positive effects of financial inclusion.
Endoscopic microscopic transpedicular thoracic discectomy: Technical note

In an effort to make thoracic discectomy simple and less invasive while using direct visualization, a 70 degrees -angled lens endoscope has been adopted to visualize the ventral aspect of the spinal cord dura mater during microsurgical thoracic discectomy via a transpedicular approach. The patient is positioned in a 60 degrees forwardly inclined lateral position with the side of the lesion facing upward. After radiographic corroboration of the correct level, a transpedicular approach is made using a 1.5-cm-diameter tubular retractor through a 2-cm-long paramedian transverse skin incision. With the aid of an operating microscope, the ipsilateral facet joint, including the upper portion of the pedicle, is removed using a high-speed drill, thus exposing the neural foramen, intervertebral disc, and upper portion of the pedicle leading to the vertebral bodies. When the herniated disc and bone spur have been removed laterally in relation to the spinal cord, creating a cavity under the operating microscope, a 4-mm-diameter rigid endoscope with a 70 degrees -angled lens is mounted to an endoscope holder so that the ventral aspect of the spinal cord dura mater can be visualized directly. With the aid of direct endoscopic visualization, the disc and bone spur, which compress the spinal cord anteriorly, are pushed away toward a cavity created at the intervertebral space and are removed using a downward-biting long-armed curette. Patients with myelopathy are kept overnight in the hospital; however, those with radiculopathy are discharged home on the same day as their operation. The surgical technique and two illustrative cases are reported.
Dragon Kill Points: The Economics of Power Gamers

World of Warcraft (WoW) is a massively multi-player online role-playing game (MMORPG). The end-game consists of complex encounters requiring highly organized groups (raids). This complexity has caused the organizing of raiding guilds (self-governing player communities). Raiding guilds have hierarchical political structures in which leaders must legitimate their positions to demand participation. In a symbiotic relationship of political structure and individual desire, guilds must guarantee advancement in tandem with individuals' acquisition of items (loot); but game mechanics make this problematic. Each end-game encounter defeated offers less loot than players needed. To compensate for this raiding guilds use DKP (intra-guild economic systems). It is DKP, I argue, that generates the political cohesion necessary for guilds to successfully engage the end-game. DKP is guild specific, but important for its effects on value and reciprocity. It creates player obligation through a rationalized system measuring c...
A modular approach to α,β-unsaturated N-aryl ketonitrones

Abstract A modular approach to α,β-unsaturated N -aryl ketonitrones has been developed. Specifically, condensation of anilines and enals followed by alkylation of the resulting α,β-unsaturated imines provided N -allyl anilines, which were subjected to oxidation with Oxone® to form α,β-unsaturated N -aryl ketonitrones. This modular approach is general and provides rapid access to diversely substituted α,β-unsaturated N -aryl ketonitrones with a single purification step in good yields.
THE LATERAL METALATION OF ISOXAZOLES. A REVIEW

(1993). THE LATERAL METALATION OF ISOXAZOLES. A REVIEW. Organic Preparations and Procedures International: Vol. 25, No. 5, pp. 515-556.
Asymmetric Synthesis with Fischer Carbene Complexes: The Development of Imidazolidinone and Oxazolidinone Complexes

Versatile, efficient reagents for asymmetric synthesis can be generated in one step from alkoxy or acetoxy Fischer carbene complexes and the commercial chiral auxiliary 1,5-dimethyl-4-phenyl-2-imidazolidinone. A review of the applications of these complexes in asymmetric synthesis is presented, as well as a summary of the other types of chiral carbene complexes that have been utilized in asymmetric synthesis.
Differentially Regulated Orthologs in Sorghum and the Subgenomes of Maize

Identifying interspecies changes in gene regulation, one of the two primary sources of phenotypic variation, is challenging on a genome-wide scale. The use of paired time-course data on cold-responsive gene expression in maize (Zea mays) and sorghum (Sorghum bicolor) allowed us to identify differentially regulated orthologs. While the majority of cold-responsive transcriptional regulation of conserved gene pairs is species specific, the initial transcriptional responses to cold appear to be more conserved than later responses. In maize, the promoters of genes with conserved transcriptional responses to cold tend to contain more micrococcal nuclease hypersensitive sites in their promoters, a proxy for open chromatin. Genes with conserved patterns of transcriptional regulation between the two species show lower ratios of nonsynonymous to synonymous substitutions. Genes involved in lipid metabolism, known to be involved in cold acclimation, tended to show consistent regulation in both species. Genes with species-specific cold responses did not cluster in particular pathways nor were they enriched in particular functional categories. We propose that cold-responsive transcriptional regulation in individual species may not be a reliable marker for function, while a core set of genes involved in perceiving and responding to cold stress are subject to functionally constrained cold-responsive regulation across the grass tribe Andropogoneae.
OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development

TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1's function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET2 and 5-methylcytosine, which is accompanied by alterations in gene expression. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.
SELECTIVE DEPROTECTION OF ALKYL T-BUTYLDIMETHYLSILYL ETHERS IN THE PRESENCE OF ARYL T-BUTYLDIMETHYLSILYL ETHERS

Abstract Alkyl TBS ethers can be selectively cleaved in high yield in the presence of aryl TBS ethers employing either in situ generated hydrogen chloride or hydrogen iodide.
Scorpionates: genesis, milestones, prognosis

Abstract The development of the polypyrazolylborate/scorpionate ligand system is traced from its inception, through its early and later stages of development, primarily on the basis of the author’s experiences and contributions.
Synthesis of (±)-cartorimine

Abstract Heating pyranulose 4 and cinnamate 2 in the presence of 2,6-di-t-butylpyridine in CH3CN afforded the [5+2] cycloadduct, which was hydrolyzed to give 13% of cartorimine ( 1 ).
Rhodium-catalyzed synthesis of a C(3) disubstituted oxindole: an approach to diazonamide A

A two step synthesis of a C(3) disubstituted oxindoles via the rhodium(II)-catalyzed coupling of diazoketone (6) and 3-methyloxindole (9) is reported.
One-step synthesis of 1-hydroxymethyl-6-aryl-2H-anthra[9,1-bc]furans, 6-benzyl-2-hydroxymethylbenzonitriles, and 3-arylmethyl-4-methylphthalimides

Abstract Titled compounds were prepared by the reaction of 2-chlorobenzyl alcohol or 2-bromobenzamide with arylacetonitriles in the presence of LDA. A mechanism in terms of an initial tandem rearrangement pathway followed by appropriate cyclization processes is proposed.
Quantum Chemical Characterization of Cycloaddition Reactions between the Hydroxyallyl Cation and Dienes of Varying Nucleophilicity

Hydroxyallyl cation prefers to undergo cycloaddition reactions with dienes in a stepwise fashion. Analysis of positive charge distribution in the intermediate formed after initial C−C bond formation provides a simple unifying method for rationalizing changes in reactivity as a function of diene nucleophilicity. Predicted product distributions are consistent with results from experimental studies. Interestingly, for the initial intermediate generated from 1,3-butadiene, [3 + 2] cycloaddition reactions are favored, but closure to form a C−O bond as the second step results in an intermediate that can undergo a low-energy Claisen rearrangement to form a seven-membered-ring product identical to that expected from compact [4 + 3] cycloaddition.
TreeToReads - a pipeline for simulating raw reads from phylogenies.

Using phylogenomic analysis tools for tracking pathogens has become standard practice in academia, public health agencies, and large industries. Using the same raw read genomic data as input, there are several different approaches being used to infer phylogenetic tree. These include many different SNP pipelines, wgMLST approaches, k-mer algorithms, whole genome alignment and others; each of these has advantages and disadvantages, some have been extensively validated, some are faster, some have higher resolution. A few of these analysis approaches are well-integrated into the regulatory process of US Federal agencies (e.g. the FDA’s SNP pipeline for tracking foodborne pathogens). However, despite extensive validation on benchmark datasets and comparison with other pipelines, we lack methods for fully exploring the effects of multiple parameter values in each pipeline that can potentially have an effect on whether the correct phylogenetic tree is recovered. To resolve this problem, we offer a program, TreeToReads, which can generate raw read data from mutated genomes simulated under a known phylogeny. This simulation pipeline allows direct comparisons of simulated and observed data in a controlled environment. At each step of these simulations, researchers can vary parameters of interest (e.g., input tree topology, amount of sequence divergence, rate of indels, read coverage, distance of reference genome, etc) to assess the effects of various parameter values on correctly calling SNPs and reconstructing an accurate tree. Such critical assessments of the accuracy and robustness of analytical pipelines are essential to progress in both research and applied settings.
Inference of epistatic effects in a key mitochondrial protein.

We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein---cytochrome c oxidase subunit 2---for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth $2Ns\ensuremath{\simeq}\ensuremath{-}5$ in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.
Identification and characterization of Gypsophila paniculata color morphs in Sleeping Bear Dunes National Lakeshore, MI, USA.

Background Gypsophila paniculata (baby's breath) is an invasive species found throughout much of the northwest United States and western Canada. Recently, plants exhibiting a different color morphology were identified within the coastal dunes along eastern Lake Michigan. The common baby's breath (G. paniculata) typically produces stems that are purple in color (purple morph), while the atypical morph has stems that are green-yellow (green-yellow morph). The purpose of this study was to characterize these newly identified morphs and determine if they are genetically distinct species from the common baby's breath in order to assess whether alternative management strategies should be employed to control these populations. Methods We sequenced two chloroplast regions, ribulose-bisphosphate carboxylase gene (rbcL), and maturase K (matK), and one nuclear region, internal transcribed spacer 2 (ITS2), from the purple morphs and green-yellow morphs collected from Sleeping Bear Dunes National Lakeshore, MI, USA (SBDNL). Sequences were aligned to reference sequences from other Gypsophila species obtained from the Barcode of Life Database and GenBank databases. We also collected seeds from wild purple morph and wild green-yellow morph plants in SBDNL. We grew the seeds in a common garden setting and characterized the proportion of green-yellow individuals produced from the two color morphs after 5-months of growth. Results Phylogenetic analyses based upon rbcL, matK, and ITS2 regions suggest that the two color morphs are not distinct species and they both belong to G. paniculata. Seeds collected from wild green-yellow morphs produced a significantly higher proportion of green-yellow individuals compared to the number produced by seeds collected from wild purple morphs. However, seeds collected from both color morphs produced more purple morphs than green-yellow morphs. Discussion Based upon these results, we propose that the two color morphs are variants of G. paniculata. Given the significant difference in the number of green-yellow morphs produced from the seeds of each morph type, we also suggest that this color difference has some genetic basis. We propose that current management continue to treat the two color morphs in a similar manner in terms of removal to prevent the further spread of this species.
Synthesis and properties of a bilirubin analog with propionic acid groups replaced by carboxyl

The unnatural bile pigment analog of bilirubin-IXα, 2,3,7,13,17,18-hexamethyl-(10H,21H,23H,24H)-bilin-1,19-dione-8,12-dicarboxylic acid (1), was synthesized as its diethyl ester by coupling 4,4′-dimethyl-3,3′-dicarboethoxydipyrrylmethane-5,5′-dialdehyde with 3,4-dimethylpyrrolin-2-one.
Are the NF4+ cations in NF4BF4 really nontetrahedral?

The crystal structure of NF4BF4 has been reexamined. The low-temperature X-ray structure and solid-state 19F MAS NMR spectra are in agreement with the conclusions reached from the vibrational spect...
Novel Iodinated Diterpenes from a Marine Cyanobacterium and Red Alga Assemblage

Tasihalides A and B have been isolated from an assemblage of a marine cyanobacterium, belonging to the genus Symploca, and an unidentified red alga. The gross structures and relative stereochemistries of these diterpenes were elucidated by spectroscopic means. In addition to possessing a novel cage structure, the tasihalides represent the only examples of iodinated diterpenes in nature.
PHRED-1 is a divergent neurexin-1 homolog that organizes muscle fibers and patterns organs during regeneration

Regeneration of body parts requires the replacement of multiple cell types. To dissect this complex process, we utilized planarian flatworms that are capable of regenerating any tissue after amputation. An RNAi screen for genes involved in regeneration of the pharynx identified a novel gene, Pharynx regeneration defective-1 (PHRED-1) as essential for normal pharynx regeneration. PHRED-1 is a predicted transmembrane protein containing EGF, Laminin G, and WD40 domains, is expressed in muscle, and has predicted homologs restricted to other lophotrochozoan species. Knockdown of PHRED-1 causes abnormal regeneration of muscle fibers in both the pharynx and body wall muscle. In addition to defects in muscle regeneration, knockdown of PHRED-1 or the bHLH transcription factor MyoD also causes defects in muscle and intestinal regeneration. Together, our data demonstrate that muscle plays a key role in restoring the structural integrity of closely associated organs, and in planarians it may form a scaffold that facilitates normal intestinal branching.
A “Site Creation” Model for Specific Adsorption of Aqueous Nucleobases, Nucleosides, and Nucleotides on Compost-Derived Humic Acid

Aqueous nucleic acid constituent solutes cytosine (1), cytidine (2), cytidine 5‘-monophosphate (3), thymine (4), thymidine (5), thymidine 5‘-monophosphate (6), uracil (7), uridine (8), uridine 5‘-monophosphate (9), adenine (10), adenosine (11), adenosine 5‘-monophosphate (12), guanosine (13), and guanosine 5‘-monophosphate (14) adsorb on compost-derived humic acid in sequential steps A, B, and C. Langmuir analysis of the isotherms gives a site capacity vi and equilibrium constant Ki for a given solute and adsorption step i that increases vA KB > KC at 25.0 °C. Data at six temperatures in the range 10.0−40.0 °C indicate that structurally related solutes like 7, 8, and 9 adsorb through their nucleobase units. Adsorption of a solute in step A, B, or C can be endothermic, thermoneutral, or exothermic. This paper uses the site capacity vi at 25.0 °C, the average site capacity over the experimental temperature range 〈vi〉, the adsorption equilibrium constant Ki at 25.0 °C, and the ad...
2,3,5-trisubstituted tetrahydrofurans by Rh-mediated cyclization of an α-diazo ester

Abstract Dirhodium(II) carboxylate catalyzed cyclization of a γ-alkoxy-α-diazo ester 1 was found to procced with substantial diasatereoselectivity, producing the 2,3,5-trisubstituted tetrahydrofurans 2a and 2b in a ratio of 4 : 1.
A FORMAL TOTAL SYNTHESIS OF (+)-TETRONOLIDE, THE AGLYCON OF THE TETROCARCINS : ENANTIO- AND DIASTEREOSELECTIVE SYNTHESES OF THE OCTAHYDRONAPHTHALENE ( BOTTOM-HALF) AND SPIROTETRONATE (TOP-HALF) FRAGMENTS

A formal total synthesis of (+)-tetronolide, the aglycon of the tetrocarcins, has been achieved by virtue of the development of highly diastereo- and enantioselective syntheses of the bottom- and top-half fragments 4 and 5 reported herein. These fragments previously served as key intermediates in Yoshii's pioneering total synthesis of (+)-tetronolide. The synthesis of the bottom-half octahydronaphthalene unit 4 features the intramolecular Diels−Alder reaction of tetraenal 20 and proceeds in 17 steps and 5−6% yield from d-glyceraldehyde pentylidene acetal 8. The synthesis of the spirotetronate fragment 5 features the highly enantioselective exo selective Diels−Alder reaction of triene 37 and chiral dienophile 25b and proceeds in 14 steps and 10% overall yield from cis-2-butene-1,4-diol (38). An enantioselective synthesis of Boeckman's top-half cyclohexene fragment 6 via the exo selective Diels−Alder reaction of diene 24 and dienophile 25a was also developed, but this route was deemed too inefficient for us...
Potential Energy Surface of SCl3

Sulfur trichloride anion is stable in the gas phase. Computational results at the G2 level indicate that SCl3- lies 99.0 kJ/mol below the dissociation products, dichlorosulfide and chloride anion, on a single-well potential energy surface. The anion has a T shape, with axial S−Cl bond lengths of 2.383 A and an equatorial S−Cl bond length of 2.068 A. Collision-induced dissociation results obtained using a flowing afterglow-tandem mass spectrometer give a DO(SCl2−Cl-) bond energy of 85 ± 8 kJ/mol.
New series CrLn8Te13Cl (Ln = Sm, Gd, Tb): pseudo-misfit-layer compounds.

The compounds CrLn8Te13Cl (Ln = Sm, Gd, Tb) have been prepared from the solid-state reaction of Ln, Cr, Te, and CrCl3 at 850 °C. These isostructural compounds crystallize in a new structure type that comprises a succession along the c axis of alternating distorted double rock-salt-type layers and a related CdI2-type layer. This structure bears some resemblance to the framework of certain misfit layer compounds.
Competence inhibition by the XrpA peptide encoded within the comX gene of Streptococcus mutans

Streptococcus mutans displays complex regulation of natural genetic competence. Competence development in S. mutans is controlled by a peptide derived from ComS (XIP); which along with the cytosolic regulator ComR controls the expression of the alternative sigma factor comX, the master regulator of competence development. Recently, a gene embedded within the coding region of comX was discovered and designated xrpA (comX regulatory peptide A). XrpA was found to be an antagonist of ComX, but the mechanism was not established. In this study, we reveal through both genomic and proteomic techniques that XrpA is the first described negative regulator of ComRS systems in streptococci. Transcriptomic and promoter activity assays in the ΔxrpA strain revealed an up-regulation of genes controlled by both the ComR- and ComX-regulons. An in vivo protein crosslinking and in vitro fluorescent polarization assays confirmed that the N-terminal region of XrpA were found to be sufficient in inhibiting ComR-XIP complex binding to ECom-box located within the comX promoter. This inhibitory activity was sufficient for decreases in PcomX activity, transformability and ComX accumulation. XrpA serving as a modulator of ComRS activity ultimately results in changes to subpopulation behaviors and cell fate during competence activation.
Aurora A inhibition limits centrosome clustering and promotes mitotic catastrophe in cells with supernumerary centrosomes

The presence of supernumerary centrosomes is prevalent in cancer, where they promote the formation of transient multipolar mitotic spindles. Active clustering of supernumerary centrosomes enables the formation of a functional bipolar spindle that is competent to complete a bipolar division. Disruption of spindle pole clustering in cancer cells promotes multipolar division and generation of non-proliferative daughter cells with compromised viability. Hence molecular pathways required for spindle pole clustering in cells with supernumerary centrosomes, but dispensable in normal cells, are promising therapeutic targets. Here we demonstrate that Aurora A kinase activity is required for spindle pole clustering in cells with extra centrosomes. While cells with two centrosomes are ultimately able to build a bipolar spindle and proceed through a normal cell division in the presence of Aurora A inhibition, cells with supernumerary centrosomes form multipolar and disorganized spindles that are not competent for chromosome segregation. Instead, following a prolonged mitosis, these cells experience catastrophic divisions that result in grossly aneuploid, and non-proliferative daughter cells. Aurora A inhibition in a panel of Acute Myeloid Leukemia cancer cells has a similarly disparate impact on cells with supernumerary centrosomes, suggesting that centrosome number and spindle polarity may serve as predictive biomarkers for response to therapeutic approaches that target Aurora A kinase function.