cssi/SciSciGPT-SciSciNet huggingface dataset:
Public Debt and Low Interest Rates

This lecture focuses on the costs of public debt when safe interest rates are low. I develop four main arguments. First, I show that the current US situation, in which safe interest rates are expected to remain below growth rates for a long time, is more the historical norm than the exception. If the future is like the past, this implies that debt rollovers, that is the issuance of debt without a later increase in taxes, may well be feasible. Put bluntly, public debt may have no fiscal cost. Second, even in the absence of fiscal costs, public debt reduces capital accumulation, and may therefore have welfare costs. I show that welfare costs may be smaller than typically assumed. The reason is that the safe rate is the risk-adjusted rate of return to capital. If it is lower than the growth rate, it indicates that the risk-adjusted rate of return to capital is in fact low. The average risky rate however also plays a role. I show how both the average risky rate and the average safe rate determine welfare outcomes. Third, I look at the evidence on the average risky rate, i.e., the average marginal product of capital. While the measured rate of earnings has been and is still quite high, the evidence from asset markets suggests that the marginal product of capital may be lower, with the difference reflecting either mismeasurement of capital or rents. This matters for debt: the lower the marginal product, the lower the welfare cost of debt. Fourth, I discuss a number of arguments against high public debt, and in particular the existence of multiple equilibria where investors believe debt to be risky and, by requiring a risk premium, increase the fiscal burden and make debt effectively more risky. This is a very relevant argument, but it does not have straightforward implications for the appropriate level of debt. My purpose in the lecture is not to argue for more public debt, especially in the current political environment. It is to have a richer discussion of the costs of debt and of fiscal policy than is currently the case.
Accounting comparability, financial reporting quality, and the pricing of accruals

Abstract This study examines the impact of accounting comparability on financial reporting quality and the extent to which financial statement users understand the implications of firms' accruals. We predict that comparability improves the information environment, which not only enhances the ability of managers to estimate accruals more accurately and signal their private information, but also improves investors' comprehension of accruals. Utilizing restatements, the mapping of accruals into cash flows, earnings persistence, and audit fees as measures of financial reporting quality, we find that prior-period comparability is associated with higher financial reporting quality. We also provide evidence that comparability is positively associated with managerial forecast accuracy and precision, consistent with comparability improving the ability of managers to predict future firm performance. Furthermore, we find that when prior-period comparability is higher, current period discretionary accruals are less positively correlated with contemporaneous returns and less negatively correlated with future returns, consistent with our prediction that comparability improves the pricing efficiency of accruals. Our results are robust to controlling for the endogeneity of accounting comparability and several different empirical model specifications. Overall, our findings suggest that enhanced accounting comparability is beneficial to both preparers and users of financial statements.
Lattice Location of Deuterium in Plasma and Gas Charged Mg Doped GaN

We have used ion channeling to examine the lattice configuration of deuterium in Mg doped GaN grown by MOCVD. The deuterium is introduced by exposure to gas phase or ECR plasmas. A density functional approach including lattice relaxation, was used to calculate total energies for various locations and charge states of hydrogen in the wurtzite Mg doped GaN lattice. Results of channeling measurements are compared with channeling simulations for hydrogen at lattice locations predicted by density functional theory.
Watt-Level All-Fiber Optical Parametric Chirped-Pulse Amplifier Working at 1300 Nm

We report Watt-level average output power near 1300 nm from an all-fiber ultrafast optical parametric chirped-pulse amplifier. Multiphoton imaging of a variety of samples with this light source shows good signal to noise ratio. © 2019 The Author(s)
MetaPred: Meta-Learning for Clinical Risk Prediction with Limited Patient Electronic Health Records

In recent years, large amounts of health data, such as patient Electronic Health Records (EHR), are becoming readily available. This provides an unprecedented opportunity for knowledge discovery and data mining algorithms to dig insights from them, which can, later on, be helpful to the improvement of the quality of care delivery. Predictive modeling of clinical risks, including in-hospital mortality, hospital readmission, chronic disease onset, condition exacerbation, etc., from patient EHR, is one of the health data analytic problems that attract lots of the interests. The reason is not only because the problem is important in clinical settings, but also is challenging when working with EHR such as sparsity, irregularity, temporality, etc. Different from applications in other domains such as computer vision and natural language processing, the data samples in medicine (patients) are relatively limited, which creates lots of troubles for building effective predictive models, especially for complicated ones such as deep learning. In this paper, we propose~\textttMetaPred, a meta-learning framework for clinical risk prediction from longitudinal patient EHR. In particular, in order to predict the target risk with limited data samples, we train a meta-learner from a set of related risk prediction tasks which learns how a good predictor is trained. The meta-learned can then be directly used in target risk prediction, and the limited available samples in the target domain can be used for further fine-tuning the model performance. The effectiveness of \textttMetaPred is tested on a real patient EHR repository from Oregon Health & Science University. We are able to demonstrate that with Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN) as base predictors, \textttMetaPred can achieve much better performance for predicting target risk with low resources comparing with the predictor trained on the limited samples available for this risk alone.
The Short and Long-Run Effects of Attending The Schools that Parents Prefer

Using meta-analysis we find that, on average, sought-after schools do not improve student test scores. A potential explanation for this result is that parents value schools that improve outcomes not well-measured by test scores. We explore this notion using both administrative and survey data from Barbados. Using a regression discontinuity design, preferred schools have better peers but do not improve short-run test scores. Consistent with the proposed explanation, the same students at the same schools have more post-secondary school completion and improved adult well-being (based on an index of educational attainment, occupational rank, earnings, and health). These long-run benefits are larger for females who also experience reduced teen motherhood. Mechanisms are explored.
Dimethoxyboron bromide – a new, efficient, regio- and chemoselective reagent for the conversion of terminal epoxides into bromohydrins

Dimethoxyboron bromide, (MeO) 2 BBr, easily prepared in excellent yield from boron tribromide and trimethyl borate, is a new, efficient, regio- and chemoselective reagent useful for the halogenative cleavage of compounds containing epoxy groups into vicinal bromohydrins in the presence of ether, acetal, ketal, N-oxide, and sulfoxide groups, at low temperatures (-78°C).
Mimicking Photosynthetic Electron and Energy Transfer

The results presented illustrate the evolution of unimolecular multicomponent artificial photosynthetic devices from simple two-component systems to pentad molecules. It is clear from these studies that it is possible to construct molecules which mimic many aspects of natural photosynthetic energy conversion. Properly designed carotenoporphyrins or carotenopyropheophorbides demonstrate carotenoid to tetrapyrrole singlet-singlet energy transfer, and therefore carotenoid antenna function. The diporphyrin-containing tetrads and pentads also evince interporphyrin singlet-singlet energy transfer, and thus mimic natural antenna effects involving tetrapyrrole donors
Isolating and Quantifying the Role of Developmental Noise in Generating Phenotypic Variation

Genotypic variation, environmental variation, and their interaction may produce variation in the developmental process and cause phenotypic differences among individuals. Developmental noise, which arises during development from stochasticity in cellular and molecular processes when genotype and environment are fixed, also contributes to phenotypic variation. While evolutionary biology has long focused on teasing apart the relative contribution of genes and environment to phenotypic variation, our understanding of the role of developmental noise has lagged due to technical difficulties in directly measuring the contribution of developmental noise. The influence of developmental noise is likely underestimated in studies of phenotypic variation due to intrinsic mechanisms within organisms that stabilize phenotypes and decrease variation. Since we are just beginning to appreciate the extent to which phenotypic variation due to stochasticity is potentially adaptive, the contribution of developmental noise to phenotypic variation must be separated and measured to fully understand its role in evolution. Here, we show that variation in the component of the developmental process corresponding to environmental and genetic factors (here treated together as a unit called the LALI-type) versus the contribution of developmental noise, can be distinguished for leopard gecko (Eublepharis macularius) head color patterns using mathematical simulations that model the role of random variation (corresponding to developmental noise) in patterning. Specifically, we modified the parameters of simulations corresponding to variation in the LALI-type to generate the full range of phenotypic variation in color pattern seen on the heads of eight leopard geckos. We observed that over the range of these parameters, variation in color pattern due to LALI-type variation exceeds that due to developmental noise in the studied gecko cohort. However, the effect of developmental noise on patterning is also substantial. Our approach addresses one of the major goals of evolutionary biology: to quantify the role of stochasticity in shaping phenotypic variation.
Rapid purification of small molecule libraries by ion exchange chromatography

Abstract Amines and acylated amines are synthesized in traditional solution phase reactions, then rapidly purified by ion exchange chromatography to yield pure products. In some instances, impurities devoid of ionizable functionality can be covalently modified prior to purification. The generic purification sequence is applicable to a variety of reactions, and is amenable to automation with commercially available equipment.
La48Br81Os8: isolated clusters in an unusual superstructure with significantly greater intercluster bonding.

Exploration of reactions in the La−Br−Z system for Z = Fe, Ru, and Os in welded Nb containers at 900−950 °C resulted in only the title phase. The La48Br81Os8 stoichiometry is very close to that of known triclinic Pr6Br10Os but with an ∼32-times larger cell, 138 independent atoms, and completely different intercluster connectivities in a complex monoclinic superstructure (a = 33.076(5) A, b = 23.466(3) A, c = 23.537(2) A, β = 110.701(4)°, P21/c (No. 14), Z = 4, 23 °C). Tetragonally compressed, ∼16 e- lanthanum octahedra centered by Os are heavily interbridged by Br, including Brf-a (f = face) and Bri-a-a functions, to increase coordination numbers about some Br (to 4) and La (to 6) and to give an average of 19.63 bonded Br/La6Os vs the usual 18. These result in a cell volume 10% less than for an equivalent (hypothetical) La6Br10Os and Br−Br contacts as short as 3.30 A. Increased polar La−Br interactions presumably drive these changes. Optimal atom sizes for this structure have been found so far only in thi...
A highly stereoselective entry to α-hydroxy carboxylic acids using d-fructose diacetonide as a chiral auxiliary

Abstract Protected α-hydroxy carboxylic acids were synthesized in moderate yield and high diastereoselectivity by alkylation of glycolate ester enolates using a d -fructose-derived chiral auxiliary. The new chiral center was assigned the ( R )-configuration based upon comparisons to the literature. Both enantiomers of the auxiliary are readily available.
Total synthesis of pawhuskin C: a directed ortho metalation approach

The total synthesis of the opioid modulator pawhuskin C has been accomplished in eight steps from methyl 3,5-dihydroxybenzoate. The key step in this sequence is a directed ortho metalation reaction conducted without protection of a benzylic alcohol and thus presumed to involve a formal dianion intermediate.
A Hard−Soft Acid−Base and DFT Analysis of Singlet−Triplet Gaps and the Addition of Singlet Carbenes to Alkenes

The electronic structures of sixteen carbenes and four alkenes calculated at the B3LYP/6-31G* level were used to carry out a hard−soft acid−base investigation of carbene singlet−triplet gaps and of the addition of carbenes to alkenes. The carbenes chosen include examples where the ground state varies from triplet to singlet state and examples that have been characterized as nucleophilic, electrophilic, or ambiphilic based on their reactivity with alkenes having varying electron demands. We confirmed that singlet−triplet gaps calculated by DFT methods with the B3LYP functional correlate well with experimentally known values of carbenes spanning over 70 kcal/mol. Correlations between electron-density-based parameters and singlet−triplet gaps, or with carbene−alkene reactivity, were analyzed to gain insight into the electronic structure of the carbenes and their acid−base tendencies. A good correlation was found between the singlet−triplet energy gap and the condensed softness for electrophilic attack at the...
Design, microwave-assisted synthesis, and photophysical properties of small molecule organic antennas for luminescence resonance energy transfer.

A highly efficient microwave-assisted method was successfully developed for the synthesis of a library of carbostyril analogues. The reaction time for synthesis of carbostyril analogues was drastically reduced from a reported 18−58 h to only 80 min. Compounds obtained directly from each synthesis were more than 90% pure and did not require any further purification. On the basis of the fluorescence spectra of the compounds in the initial library, four carbostyril analogues were designed. Two of these analogues showed very favorable fluorescence profiles and have the potential to be used as small molecule organic antennas for LRET studies.
Recent developments in the chiral synthesis of homoallylic amines via organoboranes

Among the plethora of protocols for the preparation of chiral homoallylic amines, the use of boron-based reagents remains relatively undeveloped. However, the recent ad- vances in the use of α-pinene-based versatile reagents for the synthesis of such amines con- firmed that very high enantioselectivity and outstanding diastereoselectivity can be readily achieved. Addition of the "allyl"boron reagents to various N-substituted imines provided the desired amine products in high yields and high to very high ee. The discovery that an addi- tion of 1.0 equiv of methanol or water to the "allyl"boration reaction with N-masked imines is critical allowed for higher yields and noticeably improved ee. The use of N-aluminoimines, which are not only easy to prepare by a partial reduction of nitriles, but are also relatively sta- ble for both enolizable and non-enolizable substrates, considerably expanded the scope of the reactions. In this review, the developments in the syntheses of chiral homoallylic amines using organoboranes, with the particular accent on the reagent-controlled reactions, are sum- marized. Additionally, the novel methodology for the crotyl- and alkoxyallylboration of imines using trialkylboron "ate" complexes is described.
Spatial dynamics within and between brain functional domains: A hierarchical approach to study time‐varying brain function

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FDs), as well as temporal dynamics within and between FDs. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations, from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g., the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variations provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.
Degree growth rates and index estimation in a directed preferential attachment model

Abstract Preferential attachment is widely used to model power-law behavior of degree distributions in both directed and undirected networks. In a directed preferential attachment model, despite the well-known marginal power-law degree distributions, not much investigation has been done on the joint behavior of the in- and out-degree growth. Also, statistical estimates of the marginal tail exponent of the power-law degree distribution often use the Hill estimator as one of the key summary statistics, even though no theoretical justification has been given. This paper focuses on the convergence of the joint empirical measure for in- and out-degrees and proves the consistency of the Hill estimator. To do this, we first derive the asymptotic behavior of the joint degree sequences by embedding the in- and out-degrees of a fixed node into a pair of switched birth processes with immigration and then establish the convergence of the joint tail empirical measure. From these steps, the consistency of the Hill estimators is obtained.
Novel synthesis of isoquinolines using isobenzofuran-nitrile Diels-Alder reactions.

The synthesis of isoquinolines through coupling of 2-alkynylbenzaldehyde derivatives with β-cyanocarbene complexes has been examined. The reaction involves formation of an isobenzofuran followed by intramolecular Diels−Alder reaction with the nitrile, a process with limited precedent. The unique success of this process in this system has been attributed to deoxygenation of the initial adduct to form the isoquinoline ring system.
Synthesis and Properties of CexCo4Ge6Se6

The novel, partially filled compounds CexCo4Ge6Se6 were synthesized using two methods: low-temperature interdiffusion and nucleation of ultrathin elemental layers and a bulk, high-temperature technique. The compounds were characterized by differential scanning calorimetry, powder X-ray diffraction, and electron probe microanalysis. The lattice parameters for the samples synthesized using the high-temperature technique were calculated to be 8.30 A, while the samples synthesized using the elemental deposition technique showed lattice expansion proportional to the amount of incorporated rare earth element, with lattice parameters ranging from 8.30 A for x = 0 up to a lattice parameter of 8.34 A for x = 0.2. Rietveld analysis on X-ray diffraction data for both sets of samples showed incorporation of the rare earth element into the interstitial site, up to 20% occupancy.
A mild synthesis of bis(indolyl)methanes using a deep eutectic solvent

Abstract Deep eutectic solvents (such as the combination of urea and choline chloride) are effective solvents/organocatalysts for the condensation of indole and aryl or alkenyl aldehydes to form bis(indolyl)methanes. The reaction conditions are quite mild and do not require additional Bronsted or Lewis acid catalyst, though they fail with ketones or aliphatic aldehydes. Given the inexpensive, non-toxic, and recyclable nature of the DES, these reaction conditions are simple and highly environmentally friendly.
Remarkable Rate Acceleration of Imidazole-Promoted Baylis−Hillman Reaction Involving Cyclic Enones in Basic Water Solution

The Baylis−Hillman reaction of cyclic enones was greatly accelerated in basic water solution with imidazoles as catalysts, which resulted in short reaction time, high yields, and expanding substrate scopes. Bicarbonate solution was shown to be the optimal reaction medium for the reaction in this study. The apparent “enhanced basicity” of imidazoles accounted for the rate increase in alkaline solution.
Comprehensive survey of combinatorial library synthesis: 2002.

The sixth annual review provides an accounting of 388 chemical libraries reported in the year 2002. Libraries are segregated into 10 tables, providing a convenient reference to libraries published with and without accompanying biological data. Three tables inventory solid-phase reagents and scavengers, linkers, and polymer-supported chiral ligands.
Preparation of Unsymmetrically Labeled Hydroperoxides. A Hydroxamate Ester−Nitrosation Approach

Reaction of O-tertiary alkyl arylhydroxamate esters with nitrosyl chloride gives O-tertiary alkyl aryl peresters that can be hydrolyzed to the hydroperoxide. If the hydroxamate ester carbonyl oxyge...
NMR imaging of solid polymers: Strategies for chemical‐shift selectivity

One reason that the solid-state imaging field is exciting is because of its potential to provide spatially resolved chemical information from deep inside a solid sample. To achieve this goal, methods are needed which exploit the many NMR parameters to generate image contrast. We describe two strategies for employing the chemical-shift anisotropy as a contrast mechanism in images of abundant nuclei in solid polymers. We illustrate these approaches with images which map spatial variations of molecular orientation in samples of polytetrafluoroethylene.
Cost-effective high-throughput single-haplotype iterative mapping and sequencing for complex genomic structures.

This protocol describes SHIMS 2.0, a method to generate accurate reference sequences from structurally complex genomic regions in a cost-effective, high-throughput manner. The reference sequences of structurally complex regions can be obtained only through highly accurate clone-based approaches. We and others have successfully used single-haplotype iterative mapping and sequencing (SHIMS) 1.0 to assemble structurally complex regions across the sex chromosomes of several vertebrate species and to allow for targeted improvements to the reference sequences of human autosomes. However, SHIMS 1.0 is expensive and time consuming, requiring resources that only a genome center can provide. Here we introduce SHIMS 2.0, an improved SHIMS protocol that allows even a small laboratory to generate high-quality reference sequence from complex genomic regions. Using a streamlined and parallelized library-preparation protocol, and taking advantage of inexpensive high-throughput short-read-sequencing technologies, a small laboratory with both molecular biology and bioinformatics experience can sequence and assemble 192 large-insert bacterial artificial chromosome (BAC) or fosmid clones in 1 week. In SHIMS 2.0, in contrast to other pooling strategies, each clone is sequenced with a unique barcode, thus enabling clones containing nearly identical sequences to be multiplexed in a single sequencing run and assembled separately. Relative to SHIMS 1.0, SHIMS 2.0 decreases the required cost and time by two orders of magnitude while preserving high sequencing accuracy.
The effects of financial reporting and disclosure on corporate investment: A review

Abstract A fundamental question in accounting is whether and to what extent financial reporting facilitates the allocation of capital to the right investment projects. Over the last two decades, a large and growing body of literature has contributed to our understanding of whether and why financial reporting affects investment decision-making. We review the empirical literature on this topic, provide a framework to organize this literature, and highlight opportunities for future research.
The generation of metaphosphoramidates by fragmentation of 2,3-oxaphosphabicyclo[2.2.2]octene derivatives

Abstract Phosphole oxides with N,N-diethylamino, N-mesitylamino and N-tert-butylamino substituents on phosphorus were generated in the presence of N-phenylmaleimide to give Diels-Alder adducts with the 7-phosphanorbornene framework. Products were characterized by 31P and 13C NMR spectroscopy, and in one case by 17O NMR spectroscopy. Insertion of oxygen into a P[sbnd]C bond of this strained cyclic system occurred smoothly on treatment with m-chloroperbenzoic acid. The resulting derivatives with the 2,3-oxaphosphabicyclo[2.2.2]octene ring system were characterized by 1H, 31P, and 13C NMR spectroscopy. In the case of the N-mesityl derivative, two stable isomers were formed and separated by chromatography. The full structure of one isomer was established by X-ray diffraction analysis. The ring system was fragmented on heating in toluene (110°C, 22–48 hrs) or on irradiation (30–35°C, 254 nm, 24 hrs) with the release of the P[sbnd]O bridging unit as a metaphosphoramidate (RR′N[sbnd]PO.). In the photolytic metho...
Demethylmenaquinone Methyl Transferase Is a Membrane Domain-Associated Protein Essential for Menaquinone Homeostasis in Mycobacterium smegmatis

The intracellular membrane domain (IMD) in mycobacteria is a spatially distinct region of the plasma membrane with diverse functions. Previous comparative proteomic analysis of the IMD suggested that menaquinone biosynthetic enzymes are associated with this domain. In the present study, we determined the subcellular site of these enzymes using sucrose density gradient fractionation. We found that the last two enzymes, the methyltransferase MenG, and the reductase MenJ, are associated with the IMD in Mycobacterium smegmatis. MenA, the prenyltransferase that mediates the first membrane-associated step of the menaquinone biosynthesis, is associated with the conventional plasma membrane. For MenG, we additionally showed the polar enrichment of the fluorescent protein fusion colocalizing with an IMD marker protein in situ. To start dissecting the roles of IMD-associated enzymes, we further tested the physiological significance of MenG. The deletion of menG at the endogenous genomic loci was possible only when an extra copy of the gene was present, indicating that it is an essential gene in M. smegmatis. Using a tetracycline-inducible switch, we achieved gradual and partial depletion of MenG over three consecutive 24 h sub-cultures. This partial MenG depletion resulted in progressive slowing of growth, which corroborated the observation that menG is an essential gene. Upon MenG depletion, there was a significant accumulation of MenG substrate, demethylmenaquinone, even though the cellular level of menaquinone, the reaction product, was unaffected. Furthermore, the growth retardation was coincided with a lower oxygen consumption rate and ATP accumulation. These results imply a previously unappreciated role of MenG in regulating menaquinone homeostasis within the complex spatial organization of mycobacterial plasma membrane.
Diphenylacetylene from the Base‐Catalyzed Fragmentation of 3,6‐Dihydro‐5,6‐Diphenyl‐3‐Tosyl‐1,3,4‐Oxadiazin‐2‐One

Treatment of 3,6-dihydro-5,6-diphenyl-3-tosyl-1,3,4-oxadiazin-2-one with sodium hydride in THF affords diphenylacetylene in better than 70% yield.
Triplet Alkyl Nitrenes

Review: solution and solid-state reactivity of triplet alkyl nitrenes in photolysis of azidoalkanes; 100 refs.
A workflow for visualizing human cancer biopsies using large-format electron microscopy

Recent developments in large format electron microscopy have enabled generation of images that provide detailed ultrastructural information on normal and diseased cells and tissues. Analyses of these images increase our understanding of cellular organization and interactions and disease-related changes therein. In this manuscript, we describe a workflow for two-dimensional (2D) and three-dimensional (3D) imaging, including both optical and scanning electron microscopy (SEM) methods, that allow pathologists and cancer biology researchers to identify areas of interest from human cancer biopsies. The protocols and mounting strategies described in this workflow are compatible with 2D large format EM mapping, 3D focused ion beam-SEM and serial block face-SEM. The flexibility to use diverse imaging technologies available at most academic institutions makes this workflow useful and applicable for most life science samples. Volumetric analysis of the biopsies studied here revealed morphological, organizational and ultrastructural aspects of the tumor cells and surrounding environment that cannot be revealed by conventional 2D EM imaging. Our results indicate that although 2D EM is still an important tool in many areas of diagnostic pathology, 3D images of ultrastructural relationships between both normal and cancerous cells, in combination with their extracellular matrix, enables cancer researchers and pathologists to better understand the progression of the disease and identify potential therapeutic targets.
Substructured Population Growth in the Ashkenazi Jews Inferred with Approximate Bayesian Computation

The Ashkenazi Jews (AJ) are a population isolate sharing ancestry with both European and Middle Eastern populations that has likely resided in Central Europe since at least the tenth century. Between the 11th and 16th centuries, the AJ population expanded eastward leading to two culturally distinct communities in Western/Central and Eastern Europe. Our aim was to determine whether the western and eastern groups are genetically distinct, and if so, what demographic processes contributed to population differentiation. We used Approximate Bayesian Computation to choose among models of AJ history and to infer demographic parameter values, including divergence times, effective population sizes, and levels of gene flow. For the ABC analysis, we used allele frequency spectrum and identical by descent-based statistics to capture information on a wide timescale. We also mitigated the effects of ascertainment bias when performing ABC on SNP array data by jointly modeling and inferring SNP discovery. We found that the most likely model was population differentiation between Eastern and Western AJ ∼400 years ago. The differentiation between the Eastern and Western AJ could be attributed to more extreme population growth in the Eastern AJ (0.250 per generation) than the Western AJ (0.069 per generation).
Synthesis of 2-substituted pyrrolidines from nitriles

Abstract A novel and synthetically facile production of 2-substituted pyrrolidines from commercially available nitriles is reported herein. This methodology is operationally simple, and only requires the use of an extraction and a single chromatographic purification to furnish the title compounds in high purity and very good yields.
Facile detosylation of cyclic peptides. An effective synthesis of platelet glycoprotein IIb/IIIa inhibitors

Abstract A general and effective synthesis of cyclic pentapeptides containing Arg-Gly-Asp sequence, which are potent antithrombotic agents, is reported.
Development of methylthiomethyl (MTM) protection for N1 of pyrrolo[2,3-d]pyrimidin-2,4-diones

Abstract This paper describes the application of the methylthiomethyl (MTM) protecting group for the N 1 position in differentially protected pyrrolo[2,3- d ]pyrimidin-2,4-diones. By reaction of selected systems with SO 2 Cl 2 at low temperature resulted in selective formation of N 1 -chloromethyl derivatives. Subsequent heating in aqueous THF with silica gel afforded the deprotected compounds in good yield. Selectivity in the presence of N 3 methoxymethyl (MOM) and benzyloxymethyl (BOM), and N 7 p-nitrophenethyl protection was achieved.
Ring Expansion of 4-Alkynylcyclobutenones. Synthesis of Piperidinoquinones, Highly Substituted Dihydrophenanthridines, Benzophenanthridines, and the Naturally Occurring Pyrrolophenanthridine, Assoanine

New synthetic routes to a variety of N-heterocyclic quinones and hydroquinones are described. These include thermolyses of 4-hydroxy-4-[4-N-(benzenesulfonyl)-4-aza-1,6-dialkynyl]cyclobutenones to piperidinoquinones and 4-hydroxy-4-[3-(N-phenylamino)-1-propynyl]cyclobutenones to dihydrophenanthridinediols. Included in the array of products available by this method are benzophenanthridines, indolophenanthridines, isoindoloindoles, and pyrrolophenanthridines. The methodology was employed in a five-step synthesis of the alkaloid assoanine starting with dimethyl squarate and indoline. The key step in all of these transformations is the ring expansion of appropriately substituted 4-hydroxy-4-alkynylcyclobutenones. These are envisaged to undergo electrocyclic ring opening to the corresponding enynylketenes which ring close to diradical intermediates that then lead to products via either radical additions to proximal alkyne moieties or undergo homolytic aromatic substitution to appropriately placed aryl groups. T...
Design and Synthesis of Multidentate Dinucleating Ligands Based on 1,8-Naphthyridine

Abstract Several novel multidentate dinucleating ligands based on 1,8-naphthyridine have been synthesized in which the 1,8-naphthyridine moiety serves as a bridging unit. These ligands can link two metal ions like the syn, syn coordination mode of bridging carboxylate groups encountered in a variety of dimetallic centers in biology. Stable dimetallic complexes with variable metal–metal separations and geometries readily form with the use of these ligands.
Diastereoselective addition of chlorotitanium enolate of N-acyl thiazolidinethione to O-methyl oximes: A novel, stereoselective synthesis of α, β-disubstituted β-amino carbonyl compounds via chiral auxiliary mediated azetine formation

We have discovered a novel and highly diastereoselective synthesis of azetinyl thiazolidine-2-thiones that utilizes additions of the chlorotitanium enolates of N-acyl thiazolidin-2-thiones to O-methyl aldoximes. The “anti” azetines can be subsequently converted to the corresponding α,β-disubstituted β-amino carbonyl compound with retention of stereochemistry. The formation of azetine and the product of its “hydrolytic” opening has been confirmed by X-ray crystallographic analyses.
Mechanism of the lithium-tellurium, lithium-iodine and lithium-mercury exchange reactions : hypervalent tellurium and iodine ate complexes

Abstract The lithium-tellurium exchange is among the fastest of the lithium-metalloid exchange reactions; only the lithium-iodine exchange is slightly faster. Tellurium, iodine and mercury ate complexes are formed when diphenyl telluride, iodobenzene or diphenylmercury are treated with phenyllithium in THF. The mechanism of the lithium-tellurium exchange, (as well as the Li/I and Li/Hg) proceeds through such ate complex intermediates. Monomeric phenyllithium is the reactive form of phenyllithium (the dimer does not participate detectably). Tetraphenyltellurium and triphenyliodine also form hypervalent ate complexes under suitable conditions.
PALADIN: protein alignment for functional profiling whole metagenome shotgun data.

Motivation Whole metagenome shotgun sequencing is a powerful approach for assaying the functional potential of microbial communities. We currently lack tools that efficiently and accurately align DNA reads against protein references, the technique necessary for constructing a functional profile. Here, we present PALADIN-a novel modification of the Burrows-Wheeler Aligner that provides accurate alignment, robust reporting capabilities and orders-of-magnitude improved efficiency by directly mapping in protein space. Results We compared the accuracy and efficiency of PALADIN against existing tools that employ nucleotide or protein alignment algorithms. Using simulated reads, PALADIN consistently outperformed the popular DNA read mappers BWA and NovoAlign in detected proteins, percentage of reads mapped and ontological similarity. We also compared PALADIN against four existing protein alignment tools: BLASTX, RAPSearch2, DIAMOND and Lambda, using empirically obtained reads. PALADIN yielded results seven times faster than the best performing alternative, DIAMOND and nearly 8000 times faster than BLASTX. PALADIN's accuracy was comparable to all tested solutions. Availability and implementation PALADIN was implemented in C, and its source code and documentation are available at https://github.com/twestbrookunh/paladin. Contact anthonyw@wildcats.unh.edu. Supplementary information Supplementary data are available at Bioinformatics online.
Global memory from local hysteresis in an amorphous solid

The atoms or particles within amorphous solids---like metallic glass or ice cream---tend to get stuck in one of many possible disordered arrangements. The authors explain a memory behavior in these materials by showing experimentally how one such material recalls past arrangements and thereby reports the magnitudes of past deformations. The memory emerges from the hysteresis of individual rearranging regions, and is similar to the return-point memory that is best known in ferromagnets---despite crucial differences in these materials' physics.
The New Impartial Jury Mandate

Impartiality is the cornerstone of the Constitution’s jury trial protections. Courts have historically treated impartiality as procedural in nature, meaning that the Constitution requires certain prophylactic procedures which secure a jury that is more likely to reach verdicts impartially. But in Pena-Rodriguez v. Colorado, 137 S.Ct. 855 (2017), the Supreme Court recognized for the first time an enforceable, substantive component to the mandate. There, the Court held that criminal litigants have a Sixth Amendment right to jury decisions made without reliance on extreme bias, specifically on the basis of race or national origin. The Court did not provide a standard for determining when evidence of partiality is sufficient to set aside a verdict, but made clear that an otherwise procedurally adequate decision may fall to substantive deficiencies. This Article advances a structural theory of the Constitution’s Impartial Jury Mandate, focusing on the interplay between its ex-ante procedural and ex-post substantive components. The Article argues that the mandate has traditionally taken shape as a collection of procedural guarantees because of a common law prohibition on reviewing the substance of jury deliberations. Pena-Rodriguez tosses this constraint, allowing judges for the first time to review the rationales upon which jurors base their verdicts. The Article then offers a novel approach for applying substantive impartiality more broadly by looking to the Equal Protection Clause’s tiers of scrutiny. It concludes that ex-ante procedural rules and ex-post substantive review can operate in conjunction to tease out undesirable, impermissible forms of jury bias, while still allowing for desirable, permissible forms of jury bias.
Court personnel attitudes towards medication-assisted treatment: A state-wide survey.

Abstract Background Despite its efficacy, medication-assisted treatment (MAT) is rarely available in the criminal justice system in the United States, including in problem-solving courts or diversionary settings. Previous studies have demonstrated criminal justice administrators' hostility towards MAT, especially in prisons and jails. Yet, few studies have examined attitudes among court personnel or compared beliefs among different types of personnel. Also, few studies have explored the relationship between MAT education/training and attitudes. Finally, few studies have directly compared attitudes towards methadone, oral buprenorphine, and extended-release naltrexone in the criminal justice system. Methods We modified a survey by Matusow et al. (2013) to explore justice professionals' MAT attitudes, including associations with demographic variables, court role, and previous MAT education/training. After piloting the survey, we distributed it to a convenience sample of justice professionals registered for an educational summit held in Indiana in 2018. Data was analyzed using descriptive and inferential statistical methods. Results 231 Indiana court employees who had registered for a state MAT educational summit completed the survey prior to the summit, including judges, probation officers, law enforcement personnel, attorneys, probation officers, program directors, counselors, and case managers. Overall, participants had significantly more positive attitudes towards extended-release naltrexone than towards other medications ( p value p value p value p value p Conclusion As expected, court employees' attitudes significantly differ by medication, with average attitudes towards agonist medications being more negative than attitudes towards extended-release naltrexone. Despite a larger evidence base for the efficacy of methadone and oral buprenorphine, justice personnel may have more positive attitudes towards extended-release naltrexone due to targeted marketing by the pharmaceutical manufacturer, fears about diversion or misuse of agonist medications, and historic criminal justice hostility towards agonist medications. Importantly, previous education/training regarding MAT is associated with more positive attitudes, suggesting that more awareness-raising or capacity building educational interventions are needed, especially for prosecutors and law enforcement personnel.
Improved Convergence for $\ell_\infty$ and $\ell_1$ Regression via Iteratively Reweighted Least Squares

The iteratively reweighted least squares method (IRLS) is a popular technique used in practice for solving regression problems. Various versions of this method have been proposed, but their theoretical analyses failed to capture the good practical performance. In this paper we propose a simple and natural version of IRLS for solving $\ell_\infty$ and $\ell_1$ regression, which provably converges to a $(1+\epsilon)$-approximate solution in $O(m^{1/3}\log(1/\epsilon)/\epsilon^{2/3} + \log m/\epsilon^2)$ iterations, where $m$ is the number of rows of the input matrix. Interestingly, this running time is independent of the conditioning of the input, and the dominant term of the running time depends sublinearly in $\epsilon^{-1}$, which is atypical for the optimization of non-smooth functions. This improves upon the more complex algorithms of Chin et al. (ITCS '12), and Christiano et al. (STOC '11) by a factor of at least $1/\epsilon^2$, and yields a truly efficient natural algorithm for the slime mold dynamics (Straszak-Vishnoi, SODA '16, ITCS '16, ITCS '17).
Information Asymmetries in Common-Value Auctions with Discrete Signals

We consider common-value hybrid auctions among two asymmetrically informed bidders, in which the winning bidder pays his bid with some positive probability κ and the losing bid otherwise. Under the...
Convexity of the image of a quadratic map via the relative entropy distance

Let \(\psi : {\mathbb R}^n \longrightarrow {\mathbb R}^k\) be a map defined by \(k\) positive definite quadratic forms on \({\mathbb R}^n\). We prove that the relative entropy (Kullback-Leibler) distance from the convex hull of the image of \(\psi \) to the image of \(\psi \) is bounded above by an absolute constant. More precisely, we prove that for every point \(a=\left( a_1, \ldots , a_k\right) \) in the convex hull of the image of \(\psi \) satisfying \(a_1 + \cdots + a_k=1\) there is a point \(b=\left( b_1, \ldots , b_k\right) \) in the image of \(\psi \) satisfying \(b_1 + \cdots + b_k =1\) and such that \(\sum _{i=1}^k a_i \ln \left( a_i/b_i\right) < 4.8\). Similarly, we prove that for any integer \(m\) one can choose a convex combination \(b\) of at most \(m\) points from the image of \(\psi \) such that \(\sum _{i=1}^k a_i \ln \left( a_i/b_i\right) < 17/\sqrt{m}\).
Towards Language-Universal End-to-End Speech Recognition

Building speech recognizers in multiple languages typically involves replicating a monolingual training recipe for each language, or utilizing a multi-task learning approach where models for different languages have separate output labels but share some internal parameters. In this work, we exploit recent progress in end-to-end speech recognition to create a single multilingual speech recognition system capable of recognizing any of the languages seen in training. To do so, we propose the use of a universal character set that is shared among all languages. We also create a language-specific gating mechanism within the network that can modulate the network's internal representations in a language-specific way. We evaluate our proposed approach on the Microsoft Cortana task across three languages and show that our system outperforms both the individual monolingual systems and systems built with a multi-task learning approach. We also show that this model can be used to initialize a monolingual speech recognizer, and can be used to create a bilingual model for use in code-switching scenarios.
Training Well-Generalizing Classifiers for Fairness Metrics and Other Data-Dependent Constraints

Classifiers can be trained with data-dependent constraints to satisfy fairness goals, reduce churn, achieve a targeted false positive rate, or other policy goals. We study the generalization performance for such constrained optimization problems, in terms of how well the constraints are satisfied at evaluation time, given that they are satisfied at training time. To improve generalization performance, we frame the problem as a two-player game where one player optimizes the model parameters on a training dataset, and the other player enforces the constraints on an independent validation dataset. We build on recent work in two-player constrained optimization to show that if one uses this two-dataset approach, then constraint generalization can be significantly improved. As we illustrate experimentally, this approach works not only in theory, but also in practice.