cssi/SciSciGPT-SciSciNet huggingface dataset:
Quantifying inactive lithium in lithium metal batteries

Lithium metal anodes offer high theoretical capacities (3,860 milliampere-hours per gram)1, but rechargeable batteries built with such anodes suffer from dendrite growth and low Coulombic efficiency (the ratio of charge output to charge input), preventing their commercial adoption2,3. The formation of inactive ('dead') lithium- which consists of both (electro)chemically formed Li+ compounds in the solid electrolyte interphase and electrically isolated unreacted metallic Li0 (refs 4,5)-causes capacity loss and safety hazards. Quantitatively distinguishing between Li+ in components of the solid electrolyte interphase and unreacted metallic Li0 has not been possible, owing to the lack of effective diagnostic tools. Optical microscopy6, in situ environmental transmission electron microscopy7,8, X-ray microtomography9 and magnetic resonance imaging10 provide a morphological perspective with little chemical information. Nuclear magnetic resonance11, X-ray photoelectron spectroscopy12 and cryogenic transmission electron microscopy13,14 can distinguish between Li+ in the solid electrolyte interphase and metallic Li0, but their detection ranges are limited to surfaces or local regions. Here we establish the analytical method of titration gas chromatography to quantify the contribution of unreacted metallic Li0 to the total amount of inactive lithium. We identify the unreacted metallic Li0, not the (electro)chemically formed Li+ in the solid electrolyte interphase, as the dominant source of inactive lithium and capacity loss. By coupling the unreacted metallic Li0 content to observations of its local microstructure and nanostructure by cryogenic electron microscopy (both scanning and transmission), we also establish the formation mechanism of inactive lithium in different types of electrolytes and determine the underlying cause of low Coulombic efficiency in plating and stripping (the charge and discharge processes, respectively, in a full cell) of lithium metal anodes. We propose strategies for making lithium plating and stripping more efficient so that lithium metal anodes can be used for next-generation high-energy batteries.
AutoCalib: Automatic Traffic Camera Calibration at Scale

Emerging smart cities are typically equipped with thousands of outdoor cameras. However, these cameras are usually not calibrated, i.e., information such as their precise mounting height and orientation is not available. Calibrating these cameras allows measurement of real-world distances from the video, thereby enabling a wide range of novel applications such as identifying speeding vehicles and city road planning. Unfortunately, robust camera calibration is a manual process today and is not scalable. In this article, we propose AutoCalib, a system for scalable, automatic calibration of traffic cameras. AutoCalib exploits deep learning to extract selected key-point features from car images in the video and uses a novel filtering and aggregation algorithm to automatically produce a robust estimate of the camera calibration parameters from just hundreds of samples. We have implemented AutoCalib as a service on Azure that takes in a video segment and computes the camera calibration parameters. Using video from real-world traffic cameras, we show that AutoCalib is able to estimate real-world distances with an error of less than 12%.
Formation of Tropical Anvil Clouds by Slow Evaporation

Author(s): Seeley, JT; Jeevanjee, N; Langhans, W; Romps, DM | Abstract: Tropical anvil clouds play a large role in the Earth's radiation balance, but their effect on global warming is uncertain. The conventional paradigm for these clouds attributes their existence to the rapidly declining convective mass flux below the tropopause, which implies a large source of detraining cloudy air there. Here we test this paradigm by manipulating the sources and sinks of cloudy air in cloud-resolving simulations. We find that anvils form in our simulations because of the long lifetime of upper-tropospheric cloud condensates, not because of an enhanced source of cloudy air below the tropopause. We further show that cloud lifetimes are long in the cold upper troposphere because the saturation specific humidity is much smaller there than the condensed water loading of cloudy updrafts, which causes evaporative cloud decay to act very slowly. Our results highlight the need for novel cloud-fraction schemes that align with this decay-centric framework for anvil clouds.
Audit games

Effective enforcement of laws and policies requires expending resources to prevent and detect offenders, as well as appropriate punishment schemes to deter violators. In particular, enforcement of privacy laws and policies in modern organizations that hold large volumes of personal information (e.g., hospitals, banks) relies heavily on internal audit mechanisms. We study economic considerations in the design of these mechanisms, focusing in particular on effective resource allocation and appropriate punishment schemes. We present an audit game model that is a natural generalization of a standard security game model for resource allocation with an additional punishment parameter. Computing the Stackelberg equilibrium for this game is challenging because it involves solving an optimization problem with non-convex quadratic constraints. We present an additive FPTAS that efficiently computes the solution.
Chapter 24 – Transgenerational Epigenetics

The environment can have a profound effect on development with consequences for adult health and disease. In mammals, the quality of prenatal and postnatal maternal interactions have been demonstrated to exert long-term effects on offspring and there is evidence for the role of epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and noncoding RNAs, in mediating these effects. Epidemiological and laboratory studies also suggest that parental influence may not be restricted to maternal effects; with evidence for an association between paternal experiences and divergent developmental pathways. Moreover, these parental effects may have implications for subsequent generations of offspring, such that there are transgenerational epigenetic influences. The role of epigenetics in mediating developmental plasticity both within and across generations provides a novel framework for understanding the inheritance of individual variations in phenotype and the role of the environment in inducing heritable modifications. In this review, we will discuss evidence for maternal and paternal epigenetic influence on development and the pathways through which these influences may lead to transgenerational effects.
Nonequivalent Group Design

A nonequivalent group design is a quasi-experiment used to assess the relative effects of treatments that have been assigned to groups of participants nonrandomly. Because the participants have been assigned to treatments nonrandomly, differences in the composition of the treatment groups can bias the estimates of the treatment effects. A variety of statistical methods are available for taking account of this selection bias. Each method imposes different assumptions about the nature of the selection effects, but it can be difficult to determine which set of assumptions is most appropriate in a given research setting. Researchers are advised to minimize selection differences by using groups of participants that are initially as similar as possible. Keywords: quasi-experiment; selection difference; analysis of covariance; propensity score; selection bias
Metropolitan Area Disposable Personal Income: Methodology and Results for 2001-2004

The Bureau of Economic Analysis (BEA) publishes annual estimates of state disposable personal income, the difference between state personal income and state personal current taxes. BEA also publishes annual estimates of personal income for sub-state areas, but BEA does not publish corresponding estimates of disposable personal income (DPI) due to the absence of estimates of taxes. This paper uses the methodology presented in an earlier working paper to revise and update the estimates of disposable personal income for the current 363 metropolitan statistical areas for 2001-2004.
Quadratic Hedging of Commodity and Energy Cash Flows

Commodity and energy prices are notoriously volatile. Firms routinely trade financial contracts to hedge their cash flows that are exposed to this source of risk. When markets are incomplete, which is typical in practice, eliminating such risk is impossible and attention must thus shift to its partial mitigation. This paper reviews quadratic hedging, which is an appealing financial risk management approach for this setting, considering a single commodity or energy cash flow that occurs on a given future date and assuming that financial hedging is based on trading a risk less bond and a futures contract. This work formulates this hedging problem as a Markov decision process, derives the optimal policy using stochastic dynamic programming, and characterizes the initial optimal bond position. Further, it highlights related current and potential future research.
Friction on water sliders

A body in motion tends to stay in motion but is often slowed by friction. Here we investigate the friction experienced by centimeter-sized bodies sliding on water. We show that their motion is dominated by skin friction due to the boundary layer that forms in the fluid beneath the body. We develop a simple model that considers the boundary layer as quasi-steady, and is able to capture the experimental behaviour for a range of body sizes, masses, shapes and fluid viscosities. Furthermore, we demonstrate that friction can be reduced by modification of the body’s shape or bottom topography. Our results are significant for understanding natural and artificial bodies moving at the air-water interface, and can inform the design of aerial-aquatic microrobots for environmental exploration and monitoring.
Physicians with multiple paid medical malpractice claims: Are they outliers or just unlucky?

Abstract We extend Studdert et al. (NEJM, 2016). We examine to what extent a physician who has past paid medical malpractice (“med mal”) claims in a defined prior period is more likely to have additional paid claims in a defined future period, relative to a physician with no prior-period claims. Our simulation implements a null hypothesis that paid claims are random events, with arrival risk depending on state, but not on physician-specific factors (such as technical ability, bedside manner, and communication skills). We show that even a single paid claim in the prior five years nearly quadruples the likelihood of a paid claim in the next five years, and dramatically increases the likelihood of 2+ future paid claims. More generally, the number of prior paid claims strongly predicts both the likelihood of having future paid claims and the expected number of future claims. By comparing actual to simulated probabilities, we can predict the likelihood that having a given number of paid claims is attributable to chance. We find that even for physicians in high-risk specialties in high-risk states, bad luck is highly unlikely to explain three or more claims in 5 years. Hospitals and state medical boards can use our approach to identify physicians that are likely to benefit from graduated interventions aimed at reducing future claims and patient harm.
The preparation of optically active boronic ester substituted Δ2-isoxazolines

Abstract In this paper we report our recent results in the area of nitrile oxide cycloaddition to optically active vinylboronic esters to afford optically active boronic ester substituted Δ 2 -isoxazolines. In these studies, a number of optically active diols were investigated and TADDOLs have been found to afford the best diastereoselectivity. The mixture of diastereomers obtained in these reactions can be readily purified by formation of the diethanolamine–boron complexes and recrystallized to afford the pure enantiomers.
Aqueous ring opening of N-tosylaziridine with aniline derivatives

Abstract A series of N -( p -X-phenyl)- N ′-( p -toluenesulfonyl)1,2-ethylenediamines compounds, TsN(H)CH 2 CH 2 N(H)PhX, were synthesized by the uncatalyzed ring opening reaction of N -tosylaziridine with p -X-aniline derivatives in pure water at 50 °C. No solvolysis product was observed and the only side product was that of a subsequent ring opening reactions of N -tosylaziridine with the product anilines leading to substituted diethylenetriamines, XPhN(CH 2 CH 2 NTs) 2 .
SYNTHESIS OF EXTENDED CARBAMATE AND UREA LINKED THYMIDINE DIMERS

Abstract Thymidine dimers with extended carbamate and urea linkages were synthesized. The length of the linker is expected to increase flexibility and improve duplex formation after incorporation into oligomer. 1. Part of this work has been presented: Ali, S.M.; and Bridson, P.K. Abstracts, 209th National ACS meeting, Anaheim, April 1995.
Nucleophilic Displacement Reactions of 4-(Nosyloxy)-2,3- unsaturated Esters and 2-(Nosyloxy)-3,4-unsaturated Esters

It has been found that 4-(nosyloxy)-2,3-unsaturated esters 2 undergo direct displacement with a wide variety of nucleophiles and yield 4-substituted-2,3-unsaturated products cleanly and in generally good yields. These materials thus have very good synthetic potential for the formation of densely functionalized unsaturated esters. 2-(Nosyloxy)-3,4-unsaturated esters as exemplified by methyl 2-(nosyloxy)-3-butenoate (3d) also undergo direct displacement with a range of good nucleophiles; however, the resulting substitution products are prone to rearrangements and tautomerism, as is the starting material itself, so that the synthetic utility of these compounds is limited.
Comfort Measures Orders and Hospital Transfers: Insights From the OPTIMISTIC Demonstration Project

Abstract Context Nursing facility residents and their families may identify “comfort measures” as their overall goal of care, yet some hospital transfers still occur. Objectives Describe nursing facility residents with comfort measures and their hospital transfers. Methods Mixed methods, including root cause analyses of transfers by registered nurses and interviews with a subset of health care providers and family members involved in transfers. Participants were residents in 19 central Indiana facilities with comfort measures orders who experienced unplanned transfers to the hospital between January 1, 2015 and June 30, 2016. Project demographic and clinical characteristics of the residents were obtained from the Minimum Data Set 3.0. Interviews were conducted with stakeholders involved in transfer decisions. Participants were prompted to reflect on reasons for the transfer and outcomes. Interviews were transcribed and coded using qualitative descriptive methods. Results Residents with comfort measures orders (n = 177) experienced 204 transfers. Most events were assessed as unavoidable (77%). Communication among staff, or between staff and the resident/family, primary care provider, or hospital was the most frequently noted area needing improvement (59.5%). In interviews, participants (n = 11) highlighted multiple issues, including judgments about whether decisions were “good” or “bad,” and factors that were important to decision-making, including communication, nursing facility capabilities, clinical situation, and goals of care. Conclusion Most transfers of residents with comfort measures orders were considered unavoidable. Nonetheless, we identified several opportunities for improving care processes, including communication and addressing acute changes in status.
Independent pseudogenization of CYP2J19 in penguins, owls and kiwis implicates gene in red carotenoid synthesis.

Abstract Carotenoids have important roles in bird behavior, including pigmentation for sexual signaling and improving color vision via retinal oil droplets. Yellow carotenoids are diet-derived, but red carotenoids (ketocarotenoids) are typically synthesized from yellow precursors via a carotenoid ketolase. Recent research on passerines has provided evidence that a cytochrome p450 enzyme, CYP2J19, is responsible for this reaction, though it is unclear if this function is phylogenetically restricted. Here I provide evidence that CYP2J19 is the carotenoid ketolase common to Aves using the genomes of 65 birds and the retinal transcriptomes of 15 avian taxa. CYP2J19 is functionally intact and robustly transcribed in all taxa except for several species adapted to foraging in dim light conditions. Two penguins, an owl and a kiwi show evidence of genetic lesions and relaxed selection in their genomic copy of CYP2J19 , and six owls show evidence of marked reduction in CYP2J19 retinal transcription compared to nine diurnal avian taxa. Furthermore, one of the owls appears to transcribe a CYP2J19 pseudogene. Notably, none of these taxa are known to use red carotenoids for sexual signaling and several species of owls and penguins represent the only birds known to completely lack red retinal oil droplets. The remaining avian taxa belong to groups known to possess red oil droplets, are known or expected to deposit red carotenoids in skin and/or plumage, and/or frequently forage in bright light. The loss and reduced expression of CYP2J19 is likely an adaptation to maximize retinal sensitivity, given that oil droplets reduce the amount of light available to the retina.
Fundamental concepts of photoinduced electron transfer

Photoinduced electron transfer (PET) is a term reserved to describe the transfer of an electron between photoexcited and ground-state molecules. The energetics and dynamics of PET are shown to depend on the structure of the reactants, the distance separating the reactants, the nature and polarity of the medium, and Coulombic effects. The dynamic interplay of these parameters gives rise to a variety of intermediates, including short-lived Franck-Condon intermediates, exciplexes, contact ion pairs, solvent-separated radical ions, and free ions. An understanding of the spin dynamics of PET can be helpful in sorting out various charge intermediates. The rate of PET is explored on the basis of the classical Marcus-Hush theory and nonclassical, quantum mechanical theories. Special attention is given to the role of electronic and nuclear barriers. A discussion of various procedures used to maximize the efficiency of ion-pair formation is presented, with attention to recent examples.
phylo-node: A molecular phylogenetic toolkit using Node.js.

Background Node.js is an open-source and cross-platform environment that provides a JavaScript codebase for back-end server-side applications. JavaScript has been used to develop very fast and user-friendly front-end tools for bioinformatic and phylogenetic analyses. However, no such toolkits are available using Node.js to conduct comprehensive molecular phylogenetic analysis. Results To address this problem, I have developed, phylo-node, which was developed using Node.js and provides a stable and scalable toolkit that allows the user to perform diverse molecular and phylogenetic tasks. phylo-node can execute the analysis and process the resulting outputs from a suite of software options that provides tools for read processing and genome alignment, sequence retrieval, multiple sequence alignment, primer design, evolutionary modeling, and phylogeny reconstruction. Furthermore, phylo-node enables the user to deploy server dependent applications, and also provides simple integration and interoperation with other Node modules and languages using Node inheritance patterns, and a customized piping module to support the production of diverse pipelines. Conclusions phylo-node is open-source and freely available to all users without sign-up or login requirements. All source code and user guidelines are openly available at the GitHub repository: https://github.com/dohalloran/phylo-node.
Reductive cyclization of quinone methides

The first of reduced quinone methides for the formation of carbon-carbon bonds in cyclization reactions is described. Treatment of quinone methides with SmI 2 resulted in intramolecular reaction with internal activated multiple bonds to afford 5- and 6-membered carbocycles in good yields. The activated multiple bonds use are aldehydes and α,β-unsaturated esters and nitriles
Proteome-Scale Relationships Between Local Amino Acid Composition and Protein Fates and Functions

Proteins with low-complexity domains continue to emerge as key players in both normal and pathological cellular processes. Although low-complexity domains are often grouped into a single class, individual low-complexity domains can differ substantially with respect to amino acid composition. These differences may strongly influence the physical properties, cellular regulation, and molecular functions of low-complexity domains. Therefore, we developed a bioinformatic approach to explore relationships between amino acid composition, protein metabolism, and protein function. We find that local compositional enrichment within protein sequences is associated with differences in translation efficiency, abundance, half-life, protein-protein interaction promiscuity, subcellular localization, and molecular functions of proteins on a proteome-wide scale. However, local enrichment of related amino acids is sometimes associated with opposite effects on protein regulation and function, highlighting the importance of distinguishing between different types of low-complexity domains. Furthermore, many of these effects are discernible at amino acid compositions below those required for classification as low-complexity or statistically-biased by traditional methods and in the absence of homopolymeric amino acid repeats, indicating that thresholds employed by classical methods may not reflect biologically relevant criteria. Application of our analyses to composition-driven processes, such as the formation of membraneless organelles, reveals distinct composition profiles even for closely related organelles. Collectively, these results provide a unique perspective and detailed insights into relationships between amino acid composition, protein metabolism, and protein functions.
SYNTHESIS AND STRUCTURE OF FUNCTIONALIZED DERIVATIVES OF THE CLEFT-SHAPED MOLECULE DITHIOSALICYLIDE

Conformationally rigid molecules whose structures define cavities and clefts have potential uses as receptors,1-3 catalysts,4,5 and as molecular building blocks in the construction of new materials.6 Dithiosalicylides are a class of conformationally well-defined, cleft-shaped molecules.7,8 NMR7 and X-ray crystallographic8 studies have shown that dithiosalicylide (1) adopts a boat conformation where the aromatic rings form a shallow “vshaped” pocket in which the dihedral angle between the aromatic rings is approximately 65 °.8 Although dithiosalicylides are not conformationally locked, as is the case for the structurally related Kagan’s ether1,2 and Troeger’s base3 compounds, the inversion barrier between the enantiomeric boat conformations is quite high (∼25 kcal/ mol).7 As part of investigations9-11 into the chemistry of 3H1,2-benzodithiol-3-one 1-oxide and related compounds, we recently developed a simple preparation of dithiosalicylide from 3H-1,2-benzodithiol-3-one (2).12,13 Treatment of 2 with triphenylphosphine provides good yields of 1, presumably via dimerization of a benzothietan-2-one (3) or ketene (4) intermediate (Scheme 1).14 We describe here the application of this protocol to the preparation of dithiosalicylide analogs that present larger cavities than the parent compound and to several analogs that may be amenable to further functionalization. In addition, we present the crystal structures of two dithiosalicylides that show that the compounds form discrete, selfincluded dimers and that interactions between the dimers give rise to interesting supramolecular structures.
A Comparison of the Interaction of Nitric Oxide with the Heteropolytungstic Acids H3PW12O40, H0.5Cs2.5PW12O40, HMgPW12O40, H8SiW11O38, H4SiW12O40, and H10CoW12O42

The interaction between NO and the heteropolytungstic acids (HPAs) H3PW12O40 (HPW), H0.5Cs2.5PW12O40 (HCsPW), HMgPW12O40 (HMgPW), H8SiW11O38 (HSiW11), H4SiW12O40 (HSiW), and H10CoW12O42 (HCoW) in t...
In Silico Identification of Three Types of Integrative and Conjugative Elements in Elizabethkingia anophelis Strains Isolated from around the World.

ABSTRACT Elizabethkingia anophelis is an emerging global multidrug-resistant opportunistic pathogen. We assessed the diversity among 13 complete genomes and 23 draft genomes of E. anophelis strains derived from various environmental settings and human infections from different geographic regions around the world from 1950s to the present. Putative integrative and conjugative elements (ICEs) were identified in 31/36 (86.1%) strains in the study. A total of 52 putative ICEs (including eight degenerated elements lacking integrases) were identified and categorized into three types based on the architecture of the conjugation module and the phylogeny of the relaxase, coupling protein, TraG, and TraJ protein sequences. The type II and III ICEs were found to integrate adjacent to tRNA genes, while type I ICEs integrate into intergenic regions or into a gene. The ICEs carry various cargo genes, including transcription regulator genes and genes conferring antibiotic resistance. The adaptive immune CRISPR-Cas system was found in nine strains, including five strains in which CRISPR-Cas machinery and ICEs coexist at different locations on the same chromosome. One ICE-derived spacer was present in the CRISPR locus in one strain. ICE distribution in the strains showed no geographic or temporal patterns. The ICEs in E. anophelis differ in architecture and sequence from CTnDOT, a well-studied ICE prevalent in Bacteroides spp. The categorization of ICEs will facilitate further investigations of the impact of ICE on virulence, genome epidemiology, and adaptive genomics of E. anophelis. IMPORTANCEElizabethkingia anophelis is an opportunistic human pathogen, and the genetic diversity between strains from around the world becomes apparent as more genomes are sequenced. Genome comparison identified three types of putative ICEs in 31 of 36 strains. The diversity of ICEs suggests that they had different origins. One of the ICEs was discovered previously from a large E. anophelis outbreak in Wisconsin in the United States; this ICE has integrated into the mutY gene of the outbreak strain, creating a mutator phenotype. Similar to ICEs found in many bacterial species, ICEs in E. anophelis carry various cargo genes that enable recipients to resist antibiotics and adapt to various ecological niches. The adaptive immune CRISPR-Cas system is present in nine of 36 strains. An ICE-derived spacer was found in the CRISPR locus in a strain that has no ICE, suggesting a past encounter and effective defense against ICE.
Initial Characterization of the Two ClpP Paralogs of Chlamydia trachomatis Suggests Unique Functionality for Each.

ABSTRACT Members of Chlamydia are obligate intracellular bacteria that differentiate between two distinct functional and morphological forms during their developmental cycle, elementary bodies (EBs) and reticulate bodies (RBs). EBs are nondividing small electron-dense forms that infect host cells. RBs are larger noninfectious replicative forms that develop within a membrane-bound vesicle, termed an inclusion. Given the unique properties of each developmental form of this bacterium, we hypothesized that the Clp protease system plays an integral role in proteomic turnover by degrading specific proteins from one developmental form or the other. Chlamydia spp. have five uncharacterized clp genes, clpX, clpC, two clpP paralogs, and clpB. In other bacteria, ClpC and ClpX are ATPases that unfold and feed proteins into the ClpP protease to be degraded, and ClpB is a deaggregase. Here, we focused on characterizing the ClpP paralogs. Transcriptional analyses and immunoblotting determined that these genes are expressed midcycle. Bioinformatic analyses of these proteins identified key residues important for activity. Overexpression of inactive clpP mutants in Chlamydia spp. suggested independent function of each ClpP paralog. To further probe these differences, we determined interactions between the ClpP proteins using bacterial two-hybrid assays and native gel analysis of recombinant proteins. Homotypic interactions of the ClpP proteins, but not heterotypic interactions between the ClpP paralogs, were detected. Interestingly, protease activity of ClpP2, but not ClpP1, was detected in vitro. This activity was stimulated by antibiotics known to activate ClpP, which also blocked chlamydial growth. Our data suggest the chlamydial ClpP paralogs likely serve distinct and critical roles in this important pathogen. IMPORTANCEChlamydia trachomatis is the leading cause of preventable infectious blindness and of bacterial sexually transmitted infections worldwide. Chlamydiae are developmentally regulated obligate intracellular pathogens that alternate between two functional and morphologic forms, with distinct repertoires of proteins. We hypothesize that protein degradation is a critical aspect to the developmental cycle. A key system involved in protein turnover in bacteria is the Clp protease system. Here, we characterized the two chlamydial ClpP paralogs by examining their expression in Chlamydia spp., their ability to oligomerize, and their proteolytic activity. This work will help understand the evolutionarily diverse Clp proteases in the context of intracellular organisms, which may aid in the study of other clinically relevant intracellular bacteria.
Conformation and Crystal Structure of Dipyrrinones with Oxindole Components

Pyrrole α-aldehydes (2-formyl-4,5-dimethyl-1H-pyrrole and 2-formyl-N-methylpyrrole) condense readily at C(3) of indolin-2-ones to give dipyrrinone analogs, such as (3Z)-[(4,5-dimethylpyrrol-2-yl)-methylidenyl]-indolin-2-one and (3E)-[(1-methylpyrrol-2-yl)-methylidenyl]-indolin-2-one. 1H-NMR NOE analyses and X-ray crystallography confirm the syn-(Z) configuration for the former and the syn-(E) configuration for the latter. The former is stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations of the latter indicate no energy difference between the syn and anti conformations.
Use of Stang's reagent, PhI(CN)OTf, to promote Pummerer-like oxidative cyclization of 2-(phenylthio)indoles

Abstract Treatment of various 2-(phenylthio)indoles, bearing nucleophilic groups tethered to C(3), with PhI(CN)OTf initiated an oxidative cyclization sequence that afforded 3,3-spirocyclic 2-(phenylthio)indolenines or oxindoles in moderate yield.
Modular Synthesis of Cyclic Peptidomimetics Inspired by γ-Turns†

A series of peptidomimetics based on a γ-turn motif were synthesized using a modular approach, in which N-protected piperidones were reacted with a selection of 2-hydroxyalkyl azides derived from common l-amino acids. Hydrolysis of the initially formed iminium ethers afforded the targeted series of substituted 1,4-diazepin-5-ones.
Matrix ESR Evidence for the Formation of the Bicyclo[3.2.0]hepta-2,6-diene Radical Cation Both from Ionized Quadricyclane and as an Intermediate in the Radical Cation Photoisomerization of Norbornadiene to Cycloheptatriene

We report that under matrix-isolation conditions of especially high dilution, ionization of quadricyclane leads to the bicyclo[3.2.0]hepta-2,6-diene radical cation, which is also shown to represent an important new intermediate on this much-studied C 7 H 8 .+ potential energy surface.
The Gender Pay Gap in Academia: Evidence from the Ohio State University

We utilize human resources data from The Ohio State University to assess the gender wage gap. We find a persistent gap of 11% among regular, tenure‐track faculty after accounting for fiscal year, race, clinical appointments, experience, and department. While the presence of a statistically significant gender wage gap is robust, the magnitude of the gap varies substantially depending on how the sample of interest is defined. In assessing gender wage gaps, researchers and universities must be attentive to issues of attrition and classification. Transparency regarding how estimates are affected by sample exclusions and variable definitions will yield insight into possible sources of gender bias.
Conformationally restricted tricyclic analogues of lipophilic pyrido[2,3‐d]pyrimidine antifolates

The effect of conformational restriction of the C9-N10 bridge on inhibitory potency and selectivity of trimetrexate against dihydrofolate reductase, was studied. Specifically three nonclassical tricyclic 1,3-diamino-8-(3′,4′,5′-trimethoxybenzyl)-7,9-dihydro-pyrrolo[3,4-c]pyrido[2,3-d]pyrimidin-6(5H,8H)-one (4), 1,3-diamino-8-(3′,4′,5′-trimethoxybenzyl)-9-hydro-pyrrolo[3,4-c]pyrido[2,3-d]pyrimidin-6-(8H)-one (5) and 1,3-diamino-(8H)-(3′,4′,5′-trimethoxybenzyl)-7,9-dihydro-pyrrolo[3,4-c]pyrido[2,3-d]pyrimidine (7) antifolates were synthesized. The tricyclic analogues 4 and 5 were obtained via the regiospecific cyclo-condensation of the β-keto ester 17 with 2,4,6-triaminopyrimidine. The analogue 7 was obtained via reduction of the lactam 4 with borane in tetrahydrofuran. Compounds 4, 5 and 7 were evaluated as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii and rat liver. All three compounds were more selective than trimetrexate against Pneumocystis carinii dihydrofolate reductase and significantly more selective than trimetrexate against Toxoplasma gondii dihydrofolate reductase compared with rat liver dihydrofolate reductase.
Quantitative Protein Topography Measurements by High Resolution Hydroxyl Radical Protein Footprinting Enable Accurate Molecular Model Selection.

We report an integrated workflow that allows mass spectrometry-based high-resolution hydroxyl radical protein footprinting (HR-HRPF) measurements to accurately measure the absolute average solvent accessible surface area ( ) of amino acid side chains. This approach is based on application of multi-point HR-HRPF, electron-transfer dissociation (ETD) tandem MS (MS/MS) acquisition, measurement of effective radical doses by radical dosimetry, and proper normalization of the inherent reactivity of the amino acids. The accuracy of the resulting measurements was tested by using well-characterized protein models. Moreover, we demonstrated the ability to use measurements from HR-HRPF to differentiate molecular models of high accuracy ( 4 A backbone RMSD). The ability of data from HR-HRPF to differentiate molecular model quality was found to be comparable to that of data obtained from X-ray crystal structures, indicating the accuracy and utility of HR-HRPF for evaluating the accuracy of computational models.
Radtools: R utilities for smooth navigation of medical image data

The radiology community has adopted several widely used standards for medical image files, including the popular DICOM (Digital Imaging and Communication in Medicine) and NIfTI (Neuroimaging Informatics Technology Initiative) standards. These file formats include image intensities as well as potentially extensive metadata. The NIfTI standard specifies a particular set of header fields describing the image and minimal information about the scan. DICOM headers can include any of >4,000 available metadata attributes spanning a variety of topics. NIfTI files contain all slices for an image series, while DICOM files capture single slices and image series are typically organized into a directory. Each DICOM file contains metadata for the image series as well as the individual image slice. The programming environment R is popular for data analysis due to its free and open code, active ecosystem of tools and users, and excellent system of contributed packages. Currently, many published radiological image analyses are performed with proprietary software or custom unpublished scripts. However, R is increasing in popularity in this area due to several packages for processing and analysis of image files. While these R packages handle image import and processing, no existing package makes image metadata conveniently accessible. Extracting image metadata, combining across slices, and converting to useful formats can be prohibitively cumbersome, especially for DICOM files. We present radtools, an R package for smooth navigation of medical image data. Radtools makes the problem of extracting image metadata trivially simple, providing simple functions to explore and return information in familiar R data structures. Radtools also facilitates extraction of image data and viewing of image slices. The package is freely available under the MIT license at https://github.com/pamelarussell/radtools and is easily installable from the Comprehensive R Archive Network ( https://cran.r-project.org/package=radtools ).
Temperature-dependent estimation of Gibbs energies using an updated group contribution method

Abstract Reaction-equilibrium constants determine the metabolite concentrations necessary to drive flux through metabolic pathways. Group-contribution methods offer a way to estimate reaction-equilibrium constants at wide coverage across the metabolic network. Here, we present an updated group-contribution method with 1) additional curated thermodynamic data used in fitting and 2) capabilities to calculate equilibrium constants as a function of temperature. We first collected and curated aqueous thermodynamic data, including reaction-equilibrium constants, enthalpies of reaction, Gibbs free energies of formation, enthalpies of formation, entropy changes of formation of compounds, and proton- and metal-ion-binding constants. Next, we formulated the calculation of equilibrium constants as a function of temperature and calculated the standard entropy change of formation ( Δ f S ∘ ) using a model based on molecular properties. The median absolute error in estimating Δ f S ∘ was 0.013 kJ/K/mol. We also estimated magnesium binding constants for 618 compounds using a linear regression model validated against measured data. We demonstrate the improved performance of the current method (8.17 kJ/mol in median absolute residual) over the current state-of-the-art method (11.47 kJ/mol) in estimating the 185 new reactions added in this work. The efforts here fill in gaps for thermodynamic calculations under various conditions, specifically different temperatures and metal-ion concentrations. These, to our knowledge, new capabilities empower the study of thermodynamic driving forces underlying the metabolic function of organisms living under diverse conditions.
Enantioselective synthesis of the 4-hydroxy buteneolide terminus of mucocin and related annonaceous acetogenins

Abstract The 4-hydroxy buteneolide terminus 3 , applicable to mucocin 1 and related annonaceous acetogenins, was prepared in an expeditious manner from the selenocarbonate 2 via an intramolecular acyl radical cyclization followed by an enantioselective Lewis-acid catalyzed Keck-allylation reaction.
Synthesis of D-D4FC, a biologically active nucleoside via an unprecedented palladium mediated Ferrier rearrangement-type glycosidation with an aromatization prone xylo-furanoid glycal

Abstract D-D4FC ( 1 ) is an anti-HIV agent currently under phase II clinical trial (Pharmaset Inc). Its molecular architecture is suitable for a Ferrier rearrangement kind of operation on a furanoid glycal to fix the position of the double bond and the relative stereochemistry. Despite the fact that classical Ferrier rearrangement does not work on furanoid glycals, a palladium mediated modified protocol has been developed for the glycosidation of an aromatization prone xylo-furanoid glycal ( 5 ) for the synthesis of D-D4FC.
Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling.

During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and driven by cancer stem cells characterized by CD44+CD24low/- or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal and epithelial populations both capable of tumor initiation. Less is known about these populations in non-cancerous mammary glands. From RNA sequencing, ALDH+ and ALDH-CD44+CD24- human mammary cells have epithelial-like and mesenchymal-like characteristics, respectively, with some co-expressing ALDH+ and CD44+CD24- by flow cytometry. At the single-cell level, these cells have the greatest mammosphere-forming capacity and express high levels of stemness and epithelial-to-mesenchymal transition-associated genes including ID1, SOX2, TWIST1, and ZEB2. We further identify single ALDH+ cells with a hybrid epithelial/mesenchymal phenotype that express genes associated with aggressive triple-negative breast cancers. These results highlight single-cell analyses to characterize tissue heterogeneity, even in marker-enriched populations, and identify genes and pathways that define this heterogeneity.
Improved Synthetic Utility of a Sluggish Electrophile: Reaction of Chlorosulfonyl Isocyanate with Unreactive and Reactive Alkenes

Chlorosulfonyl isocyanate (CSI) is a sluggish electrophile in reactions with electron-deficient alkenes or with many monofluoroalkenes. The efficiency of these reactions is improved at temperatures between –15 and 25 °C because, at these temperatures, CSI and the alkene are in equilibrium with an intermediate. A unimolecular reaction of the intermediate at a temperature between –15 and 25 °C is more efficient than the bimolecular reaction of the dissociated reagents above room temperature. This finding provides a method for improving the reactions of CSI with unreactive alkenes.
Synthesis of α-chiral-β,γ-unsaturated carboxylic acid derivatives using chiral auxiliaries

We report an efficient and reliable method for the synthesis of α-chiral-β,γ-unsaturated carboxylic acid derivatives using chiral auxiliaries and vinylacetic acid. Two well-established chiral auxiliaries ((S,S)-pseudoephedrine and (R)-benzyl-oxazolidinone) were chosen to test the merits of this method. Six different electrophiles were examined in the diastereoselective alkylation with both auxiliaries. The pseudoephedrine auxiliary provided isolated yields between 61 and 85% and diastereomeric ratios all greater than 96:4. Employing the same reactions as with the pseudoephedrine derivative, the corresponding oxazolidinone auxiliary provided isolated yields between 0 and 80% with diastereomeric ratios from 80:20 to 93:7.
Robust Associative Learning Is Sufficient to Explain the Structural and Dynamical Properties of Local Cortical Circuits

The ability of neural networks to associate successive states of network activity lies at the basis of many cognitive functions. Hence, we hypothesized that many ubiquitous structural and dynamical properties of local cortical networks result from associative learning. To test this hypothesis, we trained recurrent networks of excitatory and inhibitory neurons on memories composed of varying numbers of associations and compared the resulting network properties with those observed experimentally. We show that, when the network is robustly loaded with near-maximum amount of associations it can support, it develops properties that are consistent with the observed probabilities of excitatory and inhibitory connections, shapes of connection weight distributions, overexpression of specific 2- and 3-neuron motifs, distributions of connection numbers in clusters of 3-8 neurons, sustained, irregular, and asynchronous firing activity, and balance of excitation and inhibition. In addition, memories loaded into the network can be retrieved, even in the presence of noise that is comparable with the baseline variations in the postsynaptic potential. The confluence of these results suggests that many structural and dynamical properties of local cortical networks are simply a byproduct of associative learning. We predict that overexpression of excitatory-excitatory bidirectional connections observed in many cortical systems must be accompanied with underexpression of bidirectionally connected inhibitory-excitatory neuron pairs.SIGNIFICANCE STATEMENT Many structural and dynamical properties of local cortical networks are ubiquitously present across areas and species. Because synaptic connectivity is shaped by experience, we wondered whether continual learning, rather than genetic control, is responsible for producing such features. To answer this question, we developed a biologically constrained recurrent network of excitatory and inhibitory neurons capable of learning predefined sequences of network states. Embedding such associative memories into the network revealed that, when individual neurons are robustly loaded with a near-maximum amount of memories they can support, the network develops many properties that are consistent with experimental observations. Our findings suggest that basic structural and dynamical properties of local networks in the brain are simply a byproduct of learning and memory storage.
Learning Representations from EEG with Deep Recurrent-Convolutional Neural Networks

Abstract: One of the challenges in modeling cognitive events from electroencephalogram (EEG) data is finding representations that are invariant to inter- and intra-subject differences, as well as to inherent noise associated with such data. Herein, we propose a novel approach for learning such representations from multi-channel EEG time-series, and demonstrate its advantages in the context of mental load classification task. First, we transform EEG activities into a sequence of topology-preserving multi-spectral images, as opposed to standard EEG analysis techniques that ignore such spatial information. Next, we train a deep recurrent-convolutional network inspired by state-of-the-art video classification to learn robust representations from the sequence of images. The proposed approach is designed to preserve the spatial, spectral, and temporal structure of EEG which leads to finding features that are less sensitive to variations and distortions within each dimension. Empirical evaluation on the cognitive load classification task demonstrated significant improvements in classification accuracy over current state-of-the-art approaches in this field.
On preserving non-discrimination when combining expert advice

We study the interplay between sequential decision making and avoiding discrimination against protected groups, when examples arrive online and do not follow distributional assumptions. We consider the most basic extension of classical online learning: Given a class of predictors that are individually non-discriminatory with respect to a particular metric, how can we combine them to perform as well as the best predictor, while preserving non-discrimination? Surprisingly we show that this task is unachievable for the prevalent notion of "equalized odds" that requires equal false negative rates and equal false positive rates across groups. On the positive side, for another notion of non-discrimination, "equalized error rates", we show that running separate instances of the classical multiplicative weights algorithm for each group achieves this guarantee. Interestingly, even for this notion, we show that algorithms with stronger performance guarantees than multiplicative weights cannot preserve non-discrimination.
Learning Temporal Dependence from Time-Series Data with Latent Variables

We consider the setting where a collection of time series, modeled as random processes, evolve in a causal manner, and one is interested in learning the graph governing the relationships of these processes. A special case of wide interest and applicability is the setting where the noise is Gaussian and relationships are Markov and linear. We study this setting with two additional features: firstly, each random process has a hidden (latent) state, which we use to model the internal memory possessed by the variables (similar to hidden Markov models). Secondly, each variable can depend on its latent memory state through a random lag (rather than a fixed lag), thus modeling memory recall with differing lags at distinct times. Under this setting, we develop an estimator and prove that under a genericity assumption, the parameters of the model can be learned consistently. We also propose a practical adaption of this estimator, which demonstrates significant performance gains in both synthetic and real-world datasets.