cssi/SciSciGPT-SciSciNet huggingface dataset:
Shift-Share Designs: Theory and Inference

We study inference in shift-share regression designs, such as when a regional outcome is regressed on a weighted average of sectoral shocks, using regional sector shares as weights. We conduct a placebo exercise in which we estimate the effect of a shift-share regressor constructed with randomly generated sectoral shocks on actual labor market outcomes across U.S. commuting zones. Tests based on commonly used standard errors with 5% nominal significance level reject the null of no effect in up to 55% of the placebo samples. We use a stylized economic model to show that this overrejection problem arises because regression residuals are correlated across regions with similar sectoral shares, independent of their geographic location. We derive novel inference methods that are valid under arbitrary cross-regional correlation in the regression residuals. We show using popular applications of shift-share designs that our methods may lead to substantially wider confidence intervals in practice.
Evaluating Word Embeddings in Multi-label Classification Using Fine-grained Name Typing

Embedding models typically associate each word with a single real-valued vector, representing its different properties. Evaluation methods, therefore, need to analyze the accuracy and completeness of these properties in embeddings. This requires fine-grained analysis of embedding subspaces. Multi-label classification is an appropriate way to do so. We propose a new evaluation method for word embeddings based on multi-label classification given a word embedding. The task we use is fine-grained name typing: given a large corpus, find all types that a name can refer to based on the name embedding. Given the scale of entities in knowledge bases, we can build datasets for this task that are complementary to the current embedding evaluation datasets in: they are very large, contain fine-grained classes, and allow the direct evaluation of embeddings without confounding factors like sentence context.
EarlyR: A Robust Gene Expression Signature for Predicting Outcomes of Estrogen Receptor–Positive Breast Cancer

Abstract Introduction Early stage estrogen receptor (ER)-positive breast cancer may be treated with chemotherapy in addition to hormone therapy. Currently available molecular signatures assess the risk of recurrence and the benefit of chemotherapy; however, these tests may have large intermediate risk groups, limiting their usefulness. Methods The EarlyR prognostic score was developed using integrative analysis of microarray data sets and formalin-fixed, paraffin-embedded–based quantitative real-time PCR assay and validated in Affymetrix data sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier survival analysis. Concordance index was used to measure the probability of prognostic score agreement with outcome. Results The EarlyR score and categorical risk strata (EarlyR-Low, EarlyR-Int, EarlyR-High) derived from expression of ESPL1, MKI67, SPAG5, PLK1 and PGR was prognostic of 8-year distant recurrence-free interval in Affymetrix (categorical P = 3.5 × 10−14; continuous P = 8.8 × 10−15) and METABRIC (categorical P Conclusion The 5-gene EarlyR score is a robust prognostic assay that identified significantly fewer patients as intermediate risk and more as low risk than currently available assays. Further validation of the assay in clinical trial–derived cohorts is ongoing.
Regression Discontinuity Designs Using Covariates

We study regression discontinuity designs when covariates are included in the estimation. We examine local polynomial estimators that include discrete or continuous covariates in an additive separa...
ArticulatedFusion: Real-Time Reconstruction of Motion, Geometry and Segmentation Using a Single Depth Camera

This paper proposes a real-time dynamic scene reconstruction method capable of reproducing the motion, geometry, and segmentation simultaneously given live depth stream from a single RGB-D camera. Our approach fuses geometry frame by frame and uses a segmentation-enhanced node graph structure to drive the deformation of geometry in registration step. A two-level node motion optimization is proposed. The optimization space of node motions and the range of physically-plausible deformations are largely reduced by taking advantage of the articulated motion prior, which is solved by an efficient node graph segmentation method. Compared to previous fusion-based dynamic scene reconstruction methods, our experiments show robust and improved reconstruction results for tangential and occluded motions.
The U.S. patent system in transition: policy innovation and the innovation process

Abstract This paper surveys the major changes in patent policy and practice that have occured in the last two decades in the U.S., and reviews the existing analyses by the economists that attempt to measure the impacts these changes have had on the processes of technological change. It also reviews the broader theoretical and empirical literature that bears on the expected effects of changes in patent policy. Despite the significance of the policy changes and the wide availability of detailed data relating to patenting, robust conclusions regarding the empirical consequences for technological innovation of changes in patent policy are few. Possible reasons for these limited results are discussed, and possible avenues for future research are suggested.
Services Globalization in an Age of Insecurity : Rethinking Trade Cooperation

Decades of services trade negotiations have produced a plethora of rules and commitments but limited real liberalization. One reason is a form of "negotiating tunnel vision," which has led to a focus on reciprocal market opening rather than on creating the regulatory preconditions for liberalization. This paper makes four points. First, current trade disciplines are a useful but inadequate restraint on regulatory protection. Second, proposed disciplines on domestic regulation would add value but would not solve problems with the application of existing trade law and could create a hold-back problem in securing new liberalizing commitments. Third, insulating domestic consumers from international market failure is a precondition for further liberalization in many services sectors, and the relevant international bargain needs to be an exchange of regulatory commitments by exporters in return for market access commitments by importers. Fourth, such bargains create a risk of exclusion for nonparticipants that can and should be addressed. The paper illustrates these arguments drawing upon recent developments relating to data privacy, financial services, labor mobility, and competition policy.
Modeling the effect of ascites-induced compression on ovarian cancer multicellular aggregates.

ABSTRACT Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. EOC dissemination is predominantly via direct extension of cells and multicellular aggregates (MCAs) into the peritoneal cavity, which adhere to and induce retraction of peritoneal mesothelium and proliferate in the submesothelial matrix to generate metastatic lesions. Metastasis is facilitated by the accumulation of malignant ascites (500 ml to >2 l), resulting in physical discomfort and abdominal distension, and leading to poor prognosis. Although intraperitoneal fluid pressure is normally subatmospheric, an average intraperitoneal pressure of 30 cmH2O (22.1 mmHg) has been reported in women with EOC. In this study, to enable experimental evaluation of the impact of high intraperitoneal pressure on EOC progression, two new in vitro model systems were developed. Initial experiments evaluated EOC MCAs in pressure vessels connected to an Instron to apply short-term compressive force. A Flexcell Compression Plus system was then used to enable longer-term compression of MCAs in custom-designed hydrogel carriers. Results show changes in the expression of genes related to epithelial-mesenchymal transition as well as altered dispersal of compressed MCAs on collagen gels. These new model systems have utility for future analyses of compression-induced mechanotransduction and the resulting impact on cellular responses related to intraperitoneal metastatic dissemination. This article has an associated First Person interview with the first authors of the paper.
Corporate Political Strategies and Return Predictability

We assess whether observable corporate political strategies can serve as channels of value-relevant political information flow into stock prices and form the basis for profitable return predictability strategies. We document that returns of politically connected firms’ stocks lead those of their non-connected peers, suggesting that information shocks associated with new policies and other political developments become evident first in the stock prices of firms that pursue political strategies and then, with delay, in those of similar, non-connected firms.
Augmenting Robot Knowledge Consultants with Distributed Short Term Memory

Human-robot communication in situated environments involves a complex interplay between knowledge representations across a wide variety of modalities. Crucially, linguistic information must be associated with representations of objects, locations, people, and goals, which may be represented in very different ways. In previous work, we developed a Consultant Framework that facilitates modality-agnostic access to information distributed across a set of heterogeneously represented knowledge sources. In this work, we draw inspiration from cognitive science to augment these distributed knowledge sources with Short Term Memory Buffers to create an STM-augmented algorithm for referring expression generation. We then discuss the potential performance benefits of this approach and insights from cognitive science that may inform future refinements in the design of our approach.
Serum erythropoietin levels in essential thrombocythemia: phenotypic and prognostic correlates.

Abstract Background: Subnormal serum erythropoietin (EPO) level is widely accepted as a minor diagnostic criterion for polycythemia vera (PV) and has retained its value in the revised 2016 World Health Organization (WHO) classification scheme of myeloid neoplasms (Blood. 2016;127:2391). While over 80% of PV patients exhibit subnormal EPO values (Haematologica. 2004;89:1194), very little is known about the incidence, phenotypic connotation, or prognostic significance of serum EPO levels in essential thrombocythemia (ET). Methods: Study patients were recruited from the Mayo Clinic, Rochester, MN, USA. Diagnosis of ET was in strict accordance with the 2016 WHO criteria (Blood. 2016;127:2391) and only patients with EPO measurements at diagnosis or during their chronic phase were considered under the following provisions: i) no evidence of myelofibrotic or leukemic transformation; ii) no treatment with cytoreductive agents at the time of sample collection (and for those with EPO sampling at diagnosis, no prior exposure to cytoreductive therapy); iii) no hemoglobin levels below sex-adjusted values for anemia; and iv) systematic exclusion of all cases of masked PV. Serum erythropoietin levels were measured using Mayo-verified standard immune-enzymatic assay consistent with CLIA requirements with reference range between 4-21 mIU/mL. Standard statistical methods and time-to-event curves prepared using the Kaplan-Meier method were used to compare EPO-stratified groups. The JMP® Pro 13.0.0 software package was used for all analyses (SAS Institute, Cary, NC, USA). Results: Among 177 informative ET patients (median age 51 years, range 18-88; 71% females), median serum EPO concentrations were 5.2 mIU/mL (range Subnormal serum EPO levels clustered clinically with JAK2 mutations (95% vs 60%; p While serum EPO level had no bearing on overall survival data (p=0.41) (Figure 1A), subnormal circulating EPO concentrations were significantly associated with superior myelofibrosis-free survival (p=0.02) (Figure 1B) but conversely, inferior polycythemia-free survival (p=0.03) (Figure 1C). Conclusions: We conclude that subnormal serum EPO levels are relatively frequent in ET, cluster with disease features that are reminiscent of polycythemia vera, and might be associated with a lower risk of fibrotic progression. Download : Download high-res image (700KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
Snorkel DryBell: A Case Study in Deploying Weak Supervision at Industrial Scale

Labeling training data is one of the most costly bottlenecks in developing machine learning-based applications. We present a first-of-its-kind study showing how existing knowledge resources from across an organization can be used as weak supervision in order to bring development time and cost down by an order of magnitude, and introduce Snorkel DryBell, a new weak supervision management system for this setting. Snorkel DryBell builds on the Snorkel framework, extending it in three critical aspects: flexible, template-based ingestion of diverse organizational knowledge, cross-feature production serving, and scalable, sampling-free execution. On three classification tasks at Google, we find that Snorkel DryBell creates classifiers of comparable quality to ones trained with tens of thousands of hand-labeled examples, converts non-servable organizational resources to servable models for an average 52% performance improvement, and executes over millions of data points in tens of minutes.
Formalising Filesystems in the ACL2 Theorem Prover: an Application to FAT32.

In this work, we present an approach towards constructing executable specifications of existing filesystems and verifying their functional properties in a theorem proving environment. We detail an application of this approach to the FAT32 filesystem. We also detail the methodology used to build up this type of executable specification through a series of models which incrementally add features of the target filesystem. This methodology has the benefit of allowing the verification effort to start from simple models which encapsulate features common to many filesystems and which are thus suitable for reuse.
Are Sufficient Statistics Necessary? Nonparametric Measurement of Deadweight Loss from Unemployment Insurance

Central to the welfare analysis of income transfer programs is the deadweight loss associated with possible reforms. To aid analytical tractability, its measurement typically requires specifying a ...
Implications of heavy-ion induced satellite x-ray emission. I. Introduction

Regardless of how they are induced, x-ray spectra are sensitive to the chemical environment of the emitting atom and can yield information on the atomic and electronic structure of host materials. Those spectra resulting from light ion and heavy ion excitations are the main topics covered in this series of papers. Highly energetic heavy ions are capable of producing multiple innershell ionization. The resulting spectrum of x-rays from a particular target atom is composed of a complex series of satellite lines. Environmental effects give rise to the redistribution of intensity from one satellite group to another. These changes can be correlated with one satellite group to another. These changes can be correlated with bulk chemical properties (valence electron densities, effective charges, covalencies, etc.). The possibility of obtaining new chemical information (for example, in implanted materials and in metal alloys) exists but requires greater experimental and theoretical understanding of both parametric variations and the fine structure of satellite lines.
Non-deterministic Quasi-Polynomial Time is Average-Case Hard for ACC Circuits

Following the seminal work of [Williams, J. ACM 2014], in a recent breakthrough, [Murray and Williams, STOC 2018] proved that NQP (non-deterministic quasi-polynomial time) does not have polynomial-size ACC^0 circuits. We strengthen the above lower bound to an average case one, by proving that for all constants c, there is a language in NQP, which is not 1/2+1/log^c(n)-approximable by polynomial-size ACC^0 circuits. In fact, our lower bound holds for a larger circuit class: 2^(log^a n)-size ACC^0 circuits with a layer of threshold gates at the bottom, for all constants a. Our work also improves the average-case lower bound for NEXP against polynomial-size ACC circuits by [Chen, Oliveira, and Santhanam, LATIN 2018]. Our new lower bound builds on several interesting components, including: • Barrington's theorem and the existence of an NC^1-complete language which is random self-reducible. • The sub-exponential witness-size lower bound for NE against ACC^0 and the conditional non-deterministic PRG construction in [Williams, SICOMP 2016]. • An “almost'' almost-everywhere MA average-case lower bound (which strengthens the corresponding worst-case lower bound in [Murray and Williams, STOC 2018]). A PSPACE-complete language which is same-length checkable, error-correctable and also has some other nice reducibility properties, which builds on [Trevisan and Vadhan, Computational Complexity 2007]. Moreover, all its reducibility properties have corresponding low-depth non-adaptive oracle circuits. Like other lower bounds proved via the ``algorithmic approach'', the only property of ACC^0 of THR exploited by us is the existence of a non-trivial SAT algorithm for ACC^0 of THR [Williams, STOC 2014]. Therefore, for any typical circuit class l, our results apply to them as well if the corresponding non-trivial SAT (in fact, GAP-UNSAT) algorithms are discovered.
Association of Domestic Responsibilities With Career Satisfaction for Physician Mothers in Procedural vs Nonprocedural Fields.

Importance Physicians who are mothers face challenges with equal distribution of domestic duties, which can be an obstacle in career advancement and achieving overall job satisfaction. Objectives To study and report on the association between increased domestic workload and career dissatisfaction and if this association differed between proceduralists and nonproceduralists. Design, Setting, and Participants Data for this study were gathered from April 28 to May 26, 2015, via an online survey of 1712 attending physician mothers recruited from the Physician Moms Group. Statistical analysis was performed from August 25, 2017, to November 20, 2018. Main Outcomes and Measures Univariate analysis was performed for respondents who reported sole responsibility for 5 or more vs fewer than 5 main domestic tasks. Independent factors associated with career dissatisfaction or a desire to change careers were identified using a multivariate logistic regression model. Results Of the 1712 respondents, most were partnered or married (1698 [99.2%]), of which 458 (27.0%) were in procedural specialties. Overall, respondents reported having sole responsibility for most domestic tasks, and there were no statistically significant differences between procedural and nonprocedural groups. Physician mothers in procedural specialties primarily responsible for 5 or more domestic tasks reported a desire to change careers more often than those responsible for fewer than 5 tasks (105 of 191 [55.0%] vs 114 of 271 [42.1%];P = .008). This difference was not noted in physician mothers in nonprocedural specialties. In multivariate analysis of the proceduralist cohort, primary responsibility for 5 or more tasks was identified as a factor independently associated with the desire to change careers (odds ratio, 1.5; 95% CI, 1.0-2.2;P = .05). Conclusions and Relevance Physician mothers report having more domestic responsibilities than their partners. For proceduralist mothers, self-reported higher levels of domestic responsibility were associated with career dissatisfaction. Increasing numbers of mothers in the medical workforce may create a demand for more equitable distribution and/or outsourcing of domestic tasks.
Sarcomes primitifs du sein

Resume Objectif Analyser les cas de sarcomes primitifs du sein de l’Institut Bergonie. Evaluer les traitements, les facteurs pronostiques, la survie globale, la survie sans recidive. Materiels et methodes Il s’agit d’une etude retrospective de 42 cas de sarcomes primitifs du sein. Les donnees des patientes, de la maladie, du traitement et du suivi ont ete analysees. Toutes les lames d’anatomo-pathologie ont ete relues et les diagnostics confirmes. Le calcul des survies globales et sans recidive a ete realise selon la formule de Kaplan Meier et analyse par des tests de logrank. Resultats La moyenne d’âge au diagnostic est de 56,9 ans (24 a 81 ans). Cent pour cent des patientes ont eu de la chirurgie dans leur sequence therapeutique. Deux populations differentes ressortent de l’etude : les angiosarcomes et les sarcomes phyllodes. Leurs taux de survie globale et de survie sans recidive sont differents. Les angiosarcomes ont un taux de survie globale a 10 ans de 53 % et un taux de survie sans recidive a 10 ans de 55 %. Les sarcomes phyllodes ont un taux de survie globale de 100 % a 10 ans et un taux de survie sans recidive de 89 % a 10 ans (respectivement p = 0,009 et p = 0,01). Conclusion Trois facteurs pronostiques semblent essentiels : le grade histologique, les marges de resection apres chirurgie, la taille histologique. Le traitement optimal est la chirurgie par mastectomie simple sans curage axillaire. En fonction des cas, une discussion sur l’adjonction d’un traitement complementaire par radiotherapie ou chimiotherapie semble important. Une prise en charge multidisciplinaire est indispensable.
Treatment-Shortening Effect of a Novel Regimen Combining Clofazimine and High-Dose Rifapentine in Pathologically Distinct Mouse Models of Tuberculosis.

ABSTRACT Clofazimine and high-dose rifapentine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.
Session details: Demonstrations

Welcome to the SPLASH 2011 Demonstrations track. We all know that it's better to see something once than to hear about it a hundred times. Live demonstrations show the impact of software innovation in a dynamic and highly interactive setting. This track is an excellent opportunity for companies and universities to share their latest work with an experienced and technically savvy audience -- you.We have received many interesting and diverse demonstration submissions from both industry and academia, and have compiled an exciting demonstration program consisting of tools, applications, and languages in various stages of development - from prototypes and proofs of concept to mature tools and systems. Each of them contains interesting and relevant technology and should appeal to the SPLASH community.These demonstrations are not product sales pitches, but rather an opportunity for the authors to highlight, explain, and present interesting technical aspects of running applications. The sessions are intended to be two-way interactions with the audience, which has the opportunity to share ideas, interact with the authors in a small scale venue, and learn techniques used in developing innovative and high quality software. Presenters are encouraged to actively solicit feedback from the audience, which should lead to very interesting and entertaining demonstration sessions.I would like to thank this year's demonstration presenters for their hard work in bringing live demonstrations to SPLASH 2011. I am also grateful to this year's demonstrations subcommittee for their efforts to shape the 2011 demonstrations program.
New tellurites: Syntheses, structures, and characterization of K2Te4O9.3.2H2O, KGaTe6O14, and KGaTe2O6.1.8H2O

Single crystals of K2Te4O9·3.2H2O, KGaTe6O14, and KGaTe2O6·1.8H2O have been synthesized by supercritical hydrothermal methods using KOH, TeO2, and Ga2O3 as reagents. K2Te4O9·3.2H2O has a layered structure, whereas KGaTe6O14 and KGaTe2O6·1.8H2O have three-dimensional frameworks. In addition, KGaTe2O6·1.8H2O has an unprecedented open-framework tellurite topology that permits the ion exchange of Li+ and Na+. In addition, the ion-exchanged phases are highly crystalline. Crystal data: K2Te4O9·3.2H2O, triclinic, space group P1 (No. 1), with a = 7.5046(5) A, b = 10.7097(8) A, c = 10.7159(8) A, α = 60.849(1)°, β = 69.918(1)°, γ = 85.968(1)°, and Z = 2; KGaTe6O14, cubic, space group Pa-3 (No. 205), with a = 10.9267(3) A and Z = 4; KGaTe2O6·1.8H2O, triclinic, P-1 (No. 2), with a = 8.8361(6) A, b = 9.1648(6) A, c = 9.9531(7) A, α = 115.395(1)°, β = 93.973(1)°, γ = 116.011(1)°, and Z = 3.
A Systematic Evaluation of the Bleomycin A2 l-Threonine Side Chain: Its Role in Preorganization of a Compact Conformation Implicated in Sequence-Selective DNA Cleavage

The preparation and examination of 3−7 are detailed and constitute analogues of deglycobleomycin A2 (2) containing systematic modifications in the l-threonine side chain. The studies revealed a sub...
ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2

Mechanisms regulating mammalian meiotic progression are poorly understood. Here we identify mouse YTHDC2 as a critical component. A screen yielded a sterile mutant, 'ketu', caused by a Ythdc2 missense mutation. Mutant germ cells enter meiosis but proceed prematurely to aberrant metaphase and apoptosis, and display defects in transitioning from spermatogonial to meiotic gene expression programs. ketu phenocopies mutants lacking MEIOC, a YTHDC2 partner. Consistent with roles in post-transcriptional regulation, YTHDC2 is cytoplasmic, has 3'→5' RNA helicase activity in vitro, and has similarity within its YTH domain to an N6-methyladenosine recognition pocket. Orthologs are present throughout metazoans, but are diverged in nematodes and, more dramatically, Drosophilidae, where Bgcn is descended from a Ythdc2 gene duplication. We also uncover similarity between MEIOC and Bam, a Bgcn partner unique to schizophoran flies. We propose that regulation of gene expression by YTHDC2-MEIOC is an evolutionarily ancient strategy for controlling the germline transition into meiosis.
An approach to substituted 4-hydroxypyran-2-ones

We examined a method for the preparation of 4-hydroxypyran-2-ones in two steps from aryl ketones and ethyl malonyl chloride (or ethyl 2-methylmalonyl chloride). These 4-hydroxypyran-2-ones are useful precursors as they may be transformed in two steps to the 2-methoxypyran-4-ones, which is found in phenoxan—a naturally occurring compound discovered to have anti-HIV activity.
Biophysical model of axonal stimulation in epiretinal visual prostheses

Visual prostheses aim to restore vision to people blinded from degenerative photoreceptor diseases by electrically stimulating surviving neurons in the retina. However, a major challenge with epiretinal prostheses is that they may accidentally activate passing axon fibers, causing severe perceptual distortions. To investigate the effect of axonal stimulation on the retinal response, we developed a computational model of a small population of morphologically and biophysically detailed retinal ganglion cells, and simulated their response to epiretinal electrical stimulation. We found that activation thresholds of ganglion cell somas and axons varied systematically with both stimulus pulse duration and electrode-retina distance. These findings have important implications for the improvement of stimulus encoding methods for epiretinal prostheses.
Montmorillonite K 10-catalyzed regioselective addition of thiols and thiobenzoic acids onto olefins: an efficient synthesis of dithiocarboxylic esters

Abstract The addition of thiols and thiobenzoic acids onto olefins proceeded regioselectively in a Markovnikov manner in the presence of Montmorillonite K 10 (Mont K 10) clay as the catalyst to afford thioethers and thiocarboxylic S-esters, while high selectivity to anti-Markovnikov products was realized in the absence of any catalyst. Treatment of the esters with Lawesson's reagent provided the corresponding dithiocarboxylic esters in high yields.
CORRELATION OF AZIDE/SOLVENT SELECTIVITIES FOR NITRENIUM IONS WITH AB INITIO HYDRATION ENERGIES : UNDERSTANDING THE KINETIC LABILITY OF NITRENIUM IONS IN AQUEOUS SOLUTION

The experimentally determined azide/solvent selectivity data (log S) for 22 nitrenium ions (1a−v) were compared to the relative hydration energies (ΔE) calculated for these same ions at the RHF/6-31G*//3-21G level of theory. Except for the most reactive (least selective) of these ions (N-phenylnitrenium (1a), N-acetyl-N-phenylnitrenium (1b), and N-acetyl-N-(2-naphthyl)nitrenium (1d)), there is a good linear correlation of log S with ΔE that is broken only by the most selective ion for which the calculation was performed (N-(4‘-methoxy-4-biphenylyl)nitrenium (1r)). The deviation from linearity of the highly reactive ions is likely caused by the onset of preassociation trapping by N3- for ions with rate constants for solvent trapping, ks, of at least 1010 s-1. The preassociation process leads to approximately constant and low azide/solvent selectivities (log S ≈ 0.0) for these ions. Both the experimental log S values and the calculated ΔE values show that π-donor substituents in the para-position of the pro...
Oxidation of ylide precursors to vicinal tricarbonyls. Applications in vincamine alkaloid synthesis.

Abstract Attachment of carbethoxyalkyl residues to an α,β-diketo ester provides dielectrophilic species applicable to the synthesis of the vincamine alkaloids, eburnamonine and tacamonine. The required vicinal tricarbonyl aggregates were formed by oxidation of suitable ylide precursors with ozone or singlet oxygen.
Lithiation of N-Boc-Protected Ferrocenylalkylamines: Preparation of Unsymmetrical 1,1'-Disubstituted Ferrocenes

Treatment of N-Boc-1-ferrocenylethylamine or N-Boc-ferrocenylmethylamine with 2 equiv of n-BuLi results in selective N,1‘-dimetalation. Trapping of the dianions with various electrophiles is a convenient route to unsymmetrical 1,1‘-disubstituted ferrocenes. Under similar conditions, the pivalamide of 1-ferrocenylethylamine undergoes predominantly N,2-dilithiation while urea derivatives give mixtures of regioisomers.
The Apical Region of the Herpes Simplex Virus Major Capsid Protein Promotes Capsid Maturation

The herpesvirus capsid assembles in the nucleus as an immature procapsid precursor built around viral scaffold proteins. The event that initiates procapsid maturation is unknown, but it is dependent upon activation of the VP24 internal protease. Scaffold cleavage triggers angularization of the shell and its decoration with the VP26 and pUL25 capsid-surface proteins. In both the procapsid and mature angularized capsid, the apical region of the major capsid protein (VP5) is surface exposed. We investigated whether the VP5 apical region contributes to intracellular transport dynamics following entry into primary sensory neurons and also tested the hypothesis that conserved negatively charged amino acids in the apical region contribute to VP26 acquisition. To our surprise, neither hypothesis proved true. Instead, mutation of glutamic acid residues in the apical region delayed viral propagation and induced focal capsid accumulations in nuclei. Examination of capsid morphogenesis based on epitope unmasking, capsid composition, and ultrastructural analysis indicated that these clusters consisted of procapsids. The results demonstrate that, in addition to established events that occur inside the capsid, the exterior capsid shell promotes capsid morphogenesis and maturation.IMPORTANCE Herpesviruses assemble capsids and encapsidate their genomes by a process that is unlike those of other mammalian viruses but is similar to those of some bacteriophage. Many important aspects of herpesvirus morphogenesis remain enigmatic, including how the capsid shell matures into a stable angularized configuration. Capsid maturation is triggered by activation of a protease that cleaves an internal protein scaffold. We report on the fortuitous discovery that a region of the major capsid protein that is exposed on the outer surface of the capsid also contributes to capsid maturation, demonstrating that the morphogenesis of the capsid shell from its procapsid precursor to the mature angularized form is dependent upon internal and external components of the megastructure.
An Efficient Synthetic Approach to Polycyclic 2,5-Dihydropyrroles from α-Silyloxy Ketones

A three-step sequence to prepare polycyclic 2,5-dihydropyrroles from α-silyloxy ketones is presented. A Lewis acid-mediated ring fragmentation of cyclic γ-silyloxy-β-hydroxy-α-diazo esters provided tethered aldehyde ynoate intermediates which, when treated with amino acid silyl esters, underwent intramolecular azomethine ylide 1,3-dipolar cycloadditions. The 2,5-dihydropyrrole products were formed in good to excellent yield as single diastereomers.
Titanocene-Based Method for Indole Synthesis

A new approach for the construction of indoles employing the air- and moisture-stable reagent Cp2TiCl2 is described. The key steps involved are (1) the intermolecular insertion reactions of an olefin and a titanocene-stabilized benzyne complex and (2) the Pd-catalyzed aryl amination reaction. The simplicity and availability of the requisite starting materials give the method a broad scope for the preparation of polysubstituted indoles.
An efficient template synthesis of aligned boron carbide nanofibers using a single-source molecular precursor

The synthesis of aligned, monodispersed boron carbide nanofibers has been achieved by the 1025 °C pyrolysis of the compound 6,6‘-(CH2)6(B10H13)2 absorbed into a porous alumina matrix, followed by dissolution of the alumina with aqueous HF. SEM studies show that the nanofibers are ∼45 μm in length with diameters of ∼250 nm. XRD and TEM studies demonstrated that fibers pyrolyzed at 1000 °C (3 h) are amorphous, but those heated at 1025 °C (3 h) showed onset of boron carbide crystallization.
CardioCam: Leveraging Camera on Mobile Devices to Verify Users While Their Heart is Pumping

With the increasing prevalence of mobile and IoT devices (e.g., smartphones, tablets, smart-home appliances), massive private and sensitive information are stored on these devices. To prevent unauthorized access on these devices, existing user verification solutions either rely on the complexity of user-defined secrets (e.g., password) or resort to specialized biometric sensors (e.g., fingerprint reader), but the users may still suffer from various attacks, such as password theft, shoulder surfing, smudge, and forged biometrics attacks. In this paper, we propose, CardioCam, a low-cost, general, hard-to-forge user verification system leveraging the unique cardiac biometrics extracted from the readily available built-in cameras in mobile and IoT devices. We demonstrate that the unique cardiac features can be extracted from the cardiac motion patterns in fingertips, by pressing on the built-in camera. To mitigate the impacts of various ambient lighting conditions and human movements under practical scenarios, CardioCam develops a gradient-based technique to optimize the camera configuration, and dynamically selects the most sensitive pixels in a camera frame to extract reliable cardiac motion patterns. Furthermore, the morphological characteristic analysis is deployed to derive user-specific cardiac features, and a feature transformation scheme grounded on Principle Component Analysis (PCA) is developed to enhance the robustness of cardiac biometrics for effective user verification. With the prototyped system, extensive experiments involving $25$ subjects are conducted to demonstrate that CardioCam can achieve effective and reliable user verification with over $99%$ average true positive rate (TPR) while maintaining the false positive rate (FPR) as low as $4%$.
Ionic liquid media resulted in more efficient regio- and stereoselective aminohalogenation of cinnamic esters

Abstract The ionic liquid, butylmethylimidazolium tetrafluoroborate ([Bmim][BF4]), was found to be superior to classical organic solvents for the metal catalyzed regio- and stereoselective aminohalogenation of cinnamic esters. The aminohalogenation reaction of cinnamic esters with p -TsNCl 2 proceeded at a faster rate (within 12 h) in the presence of a reduced amount of catalyst (CuOTf, 6.0 mol %). Good yields (76–82%) and excellent regio- and stereoselectivity (one isomer) were achieved for eight examples.
Targeting Glutamine Metabolism and Redox State for Leukemia Therapy.

Purpose: Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the accumulation of immature myeloid precursor cells. AML is poorly responsive to conventional chemotherapy and a diagnosis of AML is usually fatal. More effective and less toxic forms of therapy are desperately needed. AML cells are known to be highly dependent on the amino acid glutamine for their survival. These studies were directed at determining the effects of glutaminase inhibition on metabolism in AML and identifying general weaknesses that can be exploited therapeutically. Experimental Design: AML cancer cell lines, primary AML cells, and mouse models of AML and acute lymphoblastic leukemia (ALL) were utilized. Results: We show that blocking glutamine metabolism through the use of a glutaminase inhibitor (CB-839) significantly impairs antioxidant glutathione production in multiple types of AML, resulting in accretion of mitochondrial reactive oxygen species (mitoROS) and apoptotic cell death. Moreover, glutaminase inhibition makes AML cells susceptible to adjuvant drugs that further perturb mitochondrial redox state, such as arsenic trioxide (ATO) and homoharringtonine (HHT). Indeed, the combination of ATO or HHT with CB-839 exacerbates mitoROS and apoptosis, and leads to more complete cell death in AML cell lines, primary AML patient samples, and in vivo using mouse models of AML. In addition, these redox-targeted combination therapies are effective in eradicating ALL cells in vitro and in vivo. Conclusions: Targeting glutamine metabolism in combination with drugs that perturb mitochondrial redox state represents an effective and potentially widely applicable therapeutic strategy for treating multiple types of leukemia.
Differential adaptation to a harsh granite outcrop habitat between sympatric Mimulus species.

Understanding which environmental variables and traits underlie adaptation to harsh environments is difficult because many traits evolve simultaneously as populations or species diverge. Here, we investigate the ecological variables and traits that underlie Mimulus laciniatus' adaptation to granite outcrops compared to its sympatric, mesic-adapted progenitor, Mimulus guttatus. We use fine-scale measurements of soil moisture and herbivory to examine differences in selective forces between the species' habitats, and measure selection on flowering time, flower size, plant height, and leaf shape in a reciprocal transplant using M. laciniatus × M. guttatus F4 hybrids. We find that differences in drought and herbivory drive survival differences between habitats, that M. laciniatus and M. guttatus are each better adapted to their native habitat, and differential habitat selection on flowering time, plant stature, and leaf shape. Although early flowering time, small stature, and lobed leaf shape underlie plant fitness in M. laciniatus' seasonally dry environment, increased plant size is advantageous in a competitive mesic environment replete with herbivores like M. guttatus'. Given that we observed divergent selection between habitats in the direction of species differences, we conclude that adaptation to different microhabitats is an important component of reproductive isolation in this sympatric species pair.
Conventional and hyperspectral time-series imaging of maize lines widely used in field trials.

Background Maize (Zea mays ssp. mays) is 1 of 3 crops, along with rice and wheat, responsible for more than one-half of all calories consumed around the world. Increasing the yield and stress tolerance of these crops is essential to meet the growing need for food. The cost and speed of plant phenotyping are currently the largest constraints on plant breeding efforts. Datasets linking new types of high-throughput phenotyping data collected from plants to the performance of the same genotypes under agronomic conditions across a wide range of environments are essential for developing new statistical approaches and computer vision-based tools. Findings A set of maize inbreds-primarily recently off patent lines-were phenotyped using a high-throughput platform at University of Nebraska-Lincoln. These lines have been previously subjected to high-density genotyping and scored for a core set of 13 phenotypes in field trials across 13 North American states in 2 years by the Genomes 2 Fields Consortium. A total of 485 GB of image data including RGB, hyperspectral, fluorescence, and thermal infrared photos has been released. Conclusions Correlations between image-based measurements and manual measurements demonstrated the feasibility of quantifying variation in plant architecture using image data. However, naive approaches to measuring traits such as biomass can introduce nonrandom measurement errors confounded with genotype variation. Analysis of hyperspectral image data demonstrated unique signatures from stem tissue. Integrating heritable phenotypes from high-throughput phenotyping data with field data from different environments can reveal previously unknown factors that influence yield plasticity.
Determination of the Relative and Absolute Stereochemistry of Fostriecin (CI-920)

The absolute stereochemistry of fostriecin (1, CI-920), a potent antitumor antibiotic presently in Phase I clinical trials at NCI, was determined to be 5R,8R,9R,11R. 2D 1H−1H NMR NOE experiments co...
Frameworks of Transition Metals and Linkers with Two or More Functional Groups

Hybrid inorganic/organic materials with open-framework or layered structures are known for many transition metals linked by functionalized organic molecules such as organic diphosphonates, polycarboxylates, polynitriles, etc., species with more than one equivalent functional groups. We have studied the effect of pH on such a system of cobaltmethylenediphosphonate and report three new compounds, Na3Co[(O3PCH2PO3)(OH)], Na2Co(O3PCH2PO3)•H2O, and Co2[(O3PCH2PO3)(H2O)], that form at very basic, moderately basic, and acidic conditions, respectively. More interestingstructural chemistry should be expected from linkers with two or more different functionalities. Both the carboxylic and phosphonic groups in carboxyethylphosphonic acid are used to coordinate to cobalt or calcium atoms in the new compounds Co3(O3PCH2CH2COO)2•6H2O and Ca(O3PCH2CH2COOH)•H2O. Taking one more step further in complexity we have also studied linkers with three different functional groups, phosphonated amino acids. The structures of two new compounds, Zn(O3PCH2CH(NH3)COO) and Zn(O3PCH2CH2CH(NH3)COO), are threedimensional frameworks made of zinccoordinated by both the carboxylic and phosphonic ends of the organic molecules. The amino groups are protonated and terminal in the voids of the frameworks.
Organic Catalysts for Photocontrolled Polymerizations

Photocontrolled polymerization is an emerging field of study in which catalysis with organic-based dyes has enabled the practical and inexpensive synthesis of well-defined, spatially and temporally controlled polymeric structures. Herein, we review the current progress in the development of organic catalysts for photoregulated polymerizations. In particular, we highlight advances in metal-free variants of photomediated controlled radical polymerizations. In addition, we examine how the unique properties of these catalysts allow the development of two mechanistically distinct chain-growth polymerizations controlled by light. 1 Introduction 2 Photocontrolled Atom-Transfer Radical Polymerization (ATRP) 3 Photocontrolled Reversible Addition–Fragmentation Chain Transfer (RAFT) 4 Reversible Complexation-Mediated Polymerization (RCMP) 5 Photocontrolled Ring-Opening Metathesis Polymerization (ROMP) 6 Conclusion and Future Outlook
"Design" in solid-state chemistry based on phase homologies. The concept of structural evolution and the new megaseries Am[M1+lSe2+l]2m [M2l+nSe2+3l+n]

An attractive way to advance the design and prediction of new compositions and structures of solid-state compounds is to identify large homologies that are amenable to chemical control. Homologies allow the systematization of phases under a common conceptual umbrella and have the potential to capture the vast majority of existing and possible compounds. We have demonstrated this in the broad system A/M‘/M‘ ‘/Se (A = K, Rb, Cs, Sr, Ba; M‘ = Pb, Sn; M‘ ‘ = Sb, Bi) by identifying the homologous “superseries” Am[M1+lSe2+l]2m[M2l+nSe2+3l+n]. This series generates a large variety of compounds with predictable composition and structure. All the compounds contain fundamental building units representing different fragments of the NaCl-type lattice. The three independent integers l, m, and n determine width, height, and shape of the building units and therefore cause structural evolution of the homologous series in three different dimensions. On the basis of this general formula one can design, in a modular fashion...
A short bout of high-intensity exercise alters ipsilesional motor cortical excitability post-stroke.

Background: Acute exercise can increase motor cortical excitability and enhance motor learning in healthy individuals, an effect known as exercise priming. Whether it has the same effects in people...
Mapping Load-Bearing in the Mammalian Spindle Reveals Local Kinetochore Fiber Anchorage that Provides Mechanical Isolation and Redundancy.

Summary Active forces generated at kinetochores move chromosomes, and the dynamic spindle must robustly anchor kinetochore fibers (k-fibers) to bear this load. The mammalian spindle bears the load of chromosome movement far from poles, but we do not know where and how—physically and molecularly—this load distributes across the spindle. In part, this is because probing spindle mechanics in live cells is difficult. Yet answering this question is key to understanding how the spindle generates and responds to force and performs its diverse mechanical functions. Here, we map load-bearing across the mammalian spindle in space-time and dissect local anchorage mechanics and mechanism. To do so, we laser-ablate single k-fibers at different spindle locations and in different molecular backgrounds and quantify the immediate relaxation of chromosomes, k-fibers, and microtubule speckles. We find that load redistribution is locally confined in all directions: along the first 3–4 μm from kinetochores, scaling with k-fiber length, and laterally within ∼2 μm of k-fiber sides, without detectable load sharing between neighboring k-fibers. A phenomenological model suggests that dense, transient crosslinks to the spindle along k-fibers bear the load of chromosome movement but that these connections do not limit the timescale of spindle reorganization. The microtubule crosslinker NuMA is needed for the local load-bearing observed, whereas Eg5 and PRC1 are not detectably required, suggesting specialization in mechanical function. Together, the data and model suggest that NuMA-mediated crosslinks locally bear load, providing mechanical isolation and redundancy while allowing spindle fluidity. These features are well suited to support robust chromosome segregation.