cssi/SciSciGPT-SciSciNet huggingface dataset:
Incremental Embedding: A Density Matrix Embedding Scheme for Molecules

The idea of using fragment embedding to circumvent the high computational scaling of accurate electronic structure methods while retaining high accuracy has been a long-standing goal for quantum chemists. Traditional fragment embedding methods mainly focus on systems composed of weakly correlated parts and are insufficient when division across chemical bonds is unavoidable. Recently, density matrix embedding theory and other methods based on the Schmidt decomposition have emerged as a fresh approach to this problem. Despite their success on model systems, these methods can prove difficult for realistic systems because they rely on either a rigid, non-overlapping partition of the system or a specification of some special sites (i.e., "edge" and "center" sites), neither of which is well-defined in general for real molecules. In this work, we present a new Schmidt decomposition-based embedding scheme called incremental embedding that allows the combination of arbitrary overlapping fragments without the knowledge of edge sites. This method forms a convergent hierarchy in the sense that higher accuracy can be obtained by using fragments involving more sites. The computational scaling for the first few levels is lower than that of most correlated wave function methods. We present results for several small molecules in atom-centered Gaussian basis sets and demonstrate that incremental embedding converges quickly with fragment size and recovers most static correlation in small basis sets even when truncated at the second lowest level.
Electro-chemo-mechanical effects of lithium incorporation in zirconium oxide

Understanding the response of functional oxides to extrinsic ion insertion is important for technological applications including electrochemical energy storage and conversion, corrosion, and electronic materials in neuromorphic computing devices. Decoupling the complicated chemical and mechanical effects of ion insertion is difficult experimentally. In this work, we assessed the effect of lithium incorporation in zirconium oxide as a model system, by performing first-principles based calculations. The chemical effect of lithium is to change the equilibria of charged defects. Lithium exists in $\mathrm{Zr}{\mathrm{O}}_{2}$ as a positively charged interstitial defect, and raises the concentration of free electrons, negatively charged oxygen interstitials, and zirconium vacancies. As a result, oxygen diffusion becomes faster by five orders of magnitude, and the total electronic conduction increases by up to five orders of magnitude in the low oxygen partial pressure regime. In the context of Zr metal oxidation, this effect accelerates oxide growth kinetics. In the context of electronic materials, it has implications for resistance modulations via ion incorporation. The mechanical effect of lithium is in changing the volume and equilibrium phase of the oxide. Lithium interstitials together with zirconium vacancies shrink the volume of the oxide matrix, release the compressive stress that is needed for stabilizing the tetragonal phase $\mathrm{Zr}{\mathrm{O}}_{2}$ at low temperature, and promote tetragonal-to-monoclinic phase transformation. By identifying these factors, we are able to mechanistically interpret experimental results in the literature for zirconium alloy corrosion in different alkali-metal hydroxide solutions. These results provide a mechanistic and quantitative understanding of lithium-accelerated corrosion of zirconium alloy, as well as, and more broadly, show the importance of considering coupled electro-chemo-mechanical effects of cation insertion in functional oxides.
Streaming Kernel PCA with $\tilde{O}(\sqrt{n})$ Random Features

We study the statistical and computational aspects of kernel principal component analysis using random Fourier features and show that under mild assumptions, $O(\sqrt{n} \log n)$ features suffices to achieve $O(1/\epsilon^2)$ sample complexity. Furthermore, we give a memory efficient streaming algorithm based on classical Oja's algorithm that achieves this rate
On the accuracy of alternative approaches for calibrating bank stress test models

Abstract Multi-year forecasts of bank performance under stressful economic conditions determine large institution regulatory capital requirements and yet the accuracy of these forecasts is undocumented. I compare the accuracies of alternative stress test model forecasts using the financial crisis as the stress scenario. Models include specifications that mimic the Federal Reserve CLASS model and alternatives that use Lasso, the AIC and an abridged set of explanatory variables. A simple single-equation Lasso model has, by far, the best forecast accuracy. Large differences in model forecast accuracy are undetectable from estimation sample statistics. These findings highlight the need for new methods for validating bank stress test models.
Firm responses to secondary stakeholder action

In this paper, we explore the conditions under which secondary stakeholder groups are likely to elicit positive firm responses. To this end, we build upon and advance Mitchell, Agle, and Wood's (1997) stakeholder saliency and identification framework by defining saliency in terms of actions, not perceptions, and by proposing that power, legitimacy, and urgency arise out of the nature of stakeholder–request–firm triplets. To test this framework, we build a unique dataset of over 600 secondary stakeholder actions within the United States, all concerning environmental issues over the period 1971–2003. Copyright © 2006 John Wiley & Sons, Ltd.
Low-temperature anomalies in disordered solids: a cold case of contested relics?

Amorphous solids manifest puzzling effects of mysterious degrees of freedom that give rise to a heat capacity and phonon scattering in great excess over what would be expected for a solid that has ...
A project‐level analysis of value creation in firms

This paper analyzes value creation in firms at the project level. We present evidence that managers facing short‐termist incentives set a lower threshold for accepting projects. Using novel data on new client and product announcements in both the U.S. and international markets, we find that the market responds less positively to a new project announcement when the firm's managers have incentives to focus on short‐term stock price performance. Furthermore, textual analysis of project announcements shows that firms with short‐termist chief executive officers use vaguer and generically positive language when introducing new projects to the marketplace.
DAGs with NO TEARS: Continuous Optimization for Structure Learning

Estimating the structure of directed acyclic graphs (DAGs, also known as Bayesian networks) is a challenging problem since the search space of DAGs is combinatorial and scales superexponentially with the number of nodes. Existing approaches rely on various local heuristics for enforcing the acyclicity constraint. In this paper, we introduce a fundamentally different strategy: we formulate the structure learning problem as a purely continuous optimization problem over real matrices that avoids this combinatorial constraint entirely. This is achieved by a novel characterization of acyclicity that is not only smooth but also exact. The resulting problem can be efficiently solved by standard numerical algorithms, which also makes implementation effortless. The proposed method outperforms existing ones, without imposing any structural assumptions on the graph such as bounded treewidth or in-degree.
Eco-Routing of Plug-In Hybrid Electric Vehicles in Transportation Networks

We study the problem of eco-routing Plug-In Hybrid Electric Vehicles (PHEVs) to minimize the overall energy consumption costs. Unlike the traditional Charge Depleting First (CDF) approaches in the literature where the power-train control strategy is fixed, we propose a Combined Routing and Power-train Control (CRPTC) algorithm which can simultaneously calculate the optimal energy route as well as the optimal power-train control strategy. To validate our method, we apply our eco-routing algorithm to a subnetwork of the Eastern Massachusetts (EMA) transportation network using actual traffic data provided by the Boston Region Metropolitan Planning Organization. As an alternative benchmark, we also simulate the traffic behavior of the network using the extracted flow data from the aforementioned traffic dataset. We show that the CRPTC approach outperforms the traditional CDF approach and we quantify the trade-off between saving energy and time in using eco-routing algorithms.
Autonomous Urban Localization and Navigation with Limited Information

Urban environments offer a challenging scenario for autonomous driving. Globally localizing information, such as a GPS signal, can be unreliable due to signal shadowing and multipath errors. Detailed a priori maps of the environment with sufficient information for autonomous navigation typically require driving the area multiple times to collect large amounts of data, substantial post-processing on that data to obtain the map, and then maintaining updates on the map as the environment changes. This paper addresses the issue of autonomous driving in an urban environment by investigating algorithms and an architecture to enable fully functional autonomous driving with limited information. An algorithm to autonomously navigate urban roadways with little to no reliance on an a priori map or GPS is developed. Localization is performed with an extended Kalman filter with odometry, compass, and sparse landmark measurement updates. Navigation is accomplished by a compass-based navigation control law. Key results from Monte Carlo studies show success rates of urban navigation under different environmental conditions. Experiments validate the simulated results and demonstrate that, for given test conditions, an expected range can be found for a given success rate.
Virulence gene profiles and phylogeny of Shiga toxin-positive Escherichia coli strains isolated from FDA regulated foods during 2010-2017.

Illnesses caused by Shiga toxin-producing Escherichia coli (STECs) can be life threatening, such as hemolytic uremic syndrome (HUS). The STECs most frequently identified by USDA’s Microbiological Data Program (MDP) carried toxin gene subtypes stx1a and/or stx2a. Here we described the genome sequences of 331 STECs isolated from foods regulated by the FDA 2010–2017, and determined their genomic identity, serotype, sequence type, virulence potential, and prevalence of antimicrobial resistance. Isolates were selected from the MDP archive, routine food testing by FDA field labs (ORA), and food testing by a contract company. Only 276 (83%) strains were confirmed as STECs by in silico analysis. Foods from which STECs were recovered included cilantro (6%), spinach (25%), lettuce (11%), and flour (9%). Phylogenetic analysis using core genome MLST revealed these STEC genomes were highly variable, with some clustering associated with ST types and serotypes. We detected 95 different sequence types (ST); several ST were previously associated with HUS: ST21 and ST29 (O26:H11), ST11 (O157:H7), ST33 (O91:H14), ST17 (O103:H2), and ST16 (O111:H-). in silico virulome analyses showed ~ 51% of these strains were potentially pathogenic [besides stx gene they also carried eae (25%) or 26% saa (26%)]. Virulence gene prevalence was also determined: stx1 only (19%); stx2 only (66%); and stx1/sxt2 (15%). Our data form a new WGS dataset that can be used to support food safety investigations and monitor the recurrence/emergence of E. coli in foods.
Compliance spillovers across taxes: The role of penalties and detection

Abstract When the tax authority increases the enforcement for one tax, what happens to the level of compliance in other taxes (spillover effect)? In this paper, we present a simple analytical model that shows that the sign of the spillover depends on how taxpayers update their beliefs about penalties and detection probabilities for one tax after observing the deterrence actions the tax agency takes for another tax. As a result, when spillovers are present, penalties and detection may not necessarily be interchangeable policy tools. We evaluate the sign of the spillover in the context of a randomized field experiment in a municipality in Argentina in a sample of about 700 taxpayers who are liable for both the property and gross-sales taxes. The evidence from the intervention indicates that the spillover from a message that increases the salience of penalties and enforcement for the property tax on the declaration in the gross-sales tax is positive. Those in the treatment group increase their reported tax by two percentage points more than the control group. This result has ample implications for researchers bringing interventions to the field and for governments’ enforcement strategies.
Disciplined geometric programming

We introduce log-log convex programs, which are optimization problems with positive variables that become convex when the variables, objective functions, and constraint functions are replaced with their logs, which we refer to as a log-log transformation. This class of problems generalizes traditional geometric programming and generalized geometric programming, and it includes interesting problems involving nonnegative matrices. We give examples of log-log convex functions, some well-known and some less so, and we develop an analog of disciplined convex programming, which we call disciplined geometric programming. Disciplined geometric programming is a subclass of log-log convex programming generated by a composition rule and a set of functions with known curvature under the log-log transformation. Finally, we describe an implementation of disciplined geometric programming as a reduction in CVXPY 1.0.
Challenges for comparative fact-finding

A paradigm shift is underway in scholarship on legal fact-finding. Recent work clearly and consistently suggests that persuasion is the product of purely comparative assessments of factual proposit...
Remote Sensing of Radiation Belt Energetic Electrons Using Lightning Triggered Upper Band Chorus

Observations of magnetospheric VLF (∼3-30 kHz) chorus being triggered by lightning induced whistlers are rare but provide a unique opportunity to remotely diagnose wave-particle interactions in the Earth's radiation belts. The observations presented here are unique in that whistlers originating from lightning in the southern hemisphere are seen to trigger upper band chorus repeatedly over the course of two hours, yielding 12 observation cases with very similar characteristics. Each whistler exhibits a distinct upper frequency cutoff and only the lowest L-shell whistler is observed to trigger upper band chorus. The observed cutoff frequencies along with L-shell and cold plasma density derived from dispersion analysis are used to estimate the anisotropy of the hot plasma distribution in the magnetosphere. Resulting anisotropy estimates are in good agreement with previous in-situ measurements and past work. While the anisotropy of the hot plasma distribution determines wave growth in the linear regime, access to the nonlinear regime requires the in situ wave amplitude to exceed the threshold for phase trapping of energetic electrons. Calculation of the threshold for each whistler shows that the upper band triggering of chorus corresponds to a lower nonlinear threshold. The results suggest that while upper band chorus is less favorable to be spontaneously generated, the conditions in this band are more conducive for triggering of the chorus instability by an external input wave.
Mitigating Advocacy Bias: The Effect Of The Reviewer Role On Tax Professional Judgment

This study examines the effect of the reviewer role on tax professionals’ advocacy bias. Prior research establishes the prevalence of advocacy bias and focuses on whether reviewers can detect preparers’ advocacy bias; however, this study examines whether the reviewer role influences tax professionals’ judgment and decision-making processes. In an experiment randomly assigning 75 tax professionals to the reviewer and preparer roles, I find professionals who occupy the reviewer role report similar advocacy attitudes to preparers but are significantly less likely to exhibit advocacy bias than preparers. Reviewers also employ a more consistent decision process than those in a preparer role. Results highlight the reviewer role as a moderator of advocacy bias, demonstrating the importance of the reviewer role for firms and clients. Understanding the effects of review responsibilities on professionals at all levels is increasingly important as firms leverage emerging technology to complete tasks traditionally assigned to less experienced professionals.
Statistics of adaptive nulling and modeling inhomogeneities in adaptive processing

Recently a generalized eigen-relation (GER) constraint was employed to model inhomogeneities in an adaptive processing context. This constraint facilitated closed-form analysis of classical adaptive detectors under a nonhomogeneous data assumption (Richmond, 1997). In this paper we re-examine the implications of this GER constraint on the statistics of adaptive nulling. We find that although the GER was originally imposed for analytic tractability it in fact preserves the essential statistical nature of an adaptive null, allowing one to model inhomogeneities in adaptive processing.
Minimizing regret in dynamic decision problems

The menu-dependent nature of regret-minimization creates subtleties when it is applied to dynamic decision problems. It is not clear whether forgone opportunities should be included in the menu. We explain commonly observed behavioral patterns as minimizing regret when forgone opportunities are present. If forgone opportunities are included, we can characterize when a form of dynamic consistency is guaranteed.
Risk Assessment of Autonomous Vehicles Using Bayesian Defense Graphs

Recent developments have made autonomous vehicles (AVs) closer to hitting our roads. However, their security is still a major concern among drivers as well as manufacturers. Although some work has been done to identify threats and possible solutions, a theoretical framework is needed to measure the security of AVs. In this paper, a simple security model based on defense graphs is proposed to quantitatively assess the likelihood of threats on components of an AV in the presence of available countermeasures. A Bayesian network (BN) analysis is then applied to obtain the associated security risk. In a case study, the model and the analysis are studied for GPS spoofing attacks, to demonstrate the effectiveness of the proposed approach for a highly vulnerable component.
Air quality impacts from the electrification of light-duty passenger vehicles in the United States

Abstract A central strategy in achieving greenhouse gas mitigation targets is the transition of vehicles from internal combustion engines to electric power. However, due to complex emission sources and nonlinear chemistry, it is unclear how such a shift might impact air quality. Here we apply a prototype version of the new-generation NOAA GFDL global Atmospheric Model, version 4 (GFDL AM4) to investigate the impact on U.S. air quality from an aggressive conversion of internal combustion vehicles to battery-powered electric vehicles (EVs). We examine a suite of scenarios designed to quantify the effect of both the magnitude of EV market penetration and the source of electricity generation used to power them. We find that summer surface ozone (O3) decreases in most locations due to widespread reductions of traffic NOx emissions. Summer fine particulate matter (PM2.5) increases on average and largest in areas with increased coal-fired power generation demands. Winter O3 increases due to reduced loss via traffic NOx while PM2.5 decreases since larger ammonium nitrate reductions offset increases in ammonium sulfate. The largest magnitude changes are simulated at the extremes of the probability distribution. Increasing the fraction of vehicles converted to EVs further decreases summer O3, while increasing the fraction of electricity generated by “emission-free” sources largely eliminates the increases in summer PM2.5 at high EV adoption fractions. Ultimately, the number of conventional vehicles replaced by EVs has a larger effect on O3 than PM2.5, while the source of the electricity for those EVs exhibit greater control on PM2.5.
The process of information systems theorizing as a discursive practice

Although there has been a growing understanding of theory in the Information Systems (IS) field in recent years, the process of theorizing is rarely addressed with contributions originating from other disciplines and little effort to coherently synthesize them. Moreover, the field’s view of theorizing has traditionally focused on the context of justification with an emphasis on collection and analysis of data in response to a research question with theory often added as an afterthought. To fill this void, we foreground the context of discovery that emphasizes the creative and often serendipitous articulation of theory by emphasizing this important stage of theorizing as a reflective and highly iterative practice. Specifically, we suggest that IS researchers engage in foundational theorizing practices to form the discourse, problematize the phenomenon of interest and leverage paradigms, and deploy generative theorizing practices through analogies, metaphors, myths, and models to develop the IS discourse. To illustrate the detailed workings of these discursive practices, we draw on key examples from IS theorizing.
The impact of shared financial decision making on overconfidence for married adults

Previous research has shown that overconfidence is associated with a decrease in the quality of decision making and, therefore, decision outcomes. However, less is known about the conditions or circumstances that reduce financial overconfidence. Using data from two national studies, this study was designed to provide insights into the dynamics of intrahousehold financial decision making by examining the role of shared decision making in reducing overconfidence bias. Findings suggest that a psychological sense of shared ownership of money is associated with lower levels of overconfidence. With regard to financial planning practice, these results suggest that married individuals who believe in shared ownership of household money tend to have lower levels of overconfidence.
Organizational turnaround: moving beyond one-size-fits-all solutions

Literature on organizational turnaround has frequently suggested, but rarely investigated, the possibility that turnaround strategies for failing organizations must be matched to the specific needs...
Systematic Advance Care Planning and Potentially Avoidable Hospitalizations of Nursing Facility Residents

Background/objectives The Optimizing Patient Transfers, Impacting Medical Quality, Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project is a successful, multicomponent demonstration project to reduce potentially avoidable hospitalizations of long-stay nursing facility residents. Systematic advance care planning (ACP) is a core component of the intervention, based on research suggesting ACP is associated with decreased hospitalizations of nursing facility residents. The purpose of this study was to describe associations between ACP documentation resulting from the OPTIMISTIC intervention and hospitalizations. Design Specially trained project nurses were embedded in 19 nursing facilities and systematically engaged in ACP as part of a larger demonstration project. Participants Residents (n = 1482) enrolled in the demonstration project for a minimum of 30 days between January 1, 2015, and June 30, 2016. Measurements ACP status: (1) Physician Orders for Scope of Treatment (POST) comfort measures or do not hospitalize (DNH) orders; (2) ACP orders with no hospitalization limit (eg, code status only); and (3) no ACP (potentially avoidable and all-cause hospitalizations per 1000 resident days). Results Residents with POST comfort measures/DNH orders (33.2% or n = 493) were less likely than residents with no ACP (14.7% or n = 218) to experience a potentially avoidable hospitalization (P = .001) or all-cause hospitalization (P = .001). These differences became statistically nonsignificant after adjusting for age, functional status, and cognitive functioning. Conclusion In this successful multicomponent demonstration project to reduce potentially avoidable hospitalizations, ACP outcomes were not associated with hospitalization rates of nursing facility residents after adjusting for resident characteristics. These findings highlight the challenge of measuring the contributions of individual components of complex, multicomponent interventions. Associations between lower hospitalization rates and ACP completion may be influenced by contextual factors, such as clinical expertise and resources to manage acute conditions leading to hospitalization, in addition to interventions to increase ACP. J Am Geriatr Soc 67:1649-1655, 2019.
Views of institutional leaders on maintaining humanism in today's practice.

Abstract Objective To explore leadership perspectives on how to maintain high quality efficient care that is also person-centered and humanistic. Methods The authors interviewed and collected narrative transcripts from a convenience sample of 32 institutional healthcare leaders at seven U.S. medical schools. The institutional leaders were asked to identify factors that either promoted or inhibited humanistic practice. A subset of authors used the constant comparative method to perform qualitative analysis of the interview transcripts. They reached thematic saturation by consensus on the major themes and illustrative examples after six conference calls. Results Institutional healthcare leaders supported vision statements, policies, organized educational and faculty development programs, role modeling including their own, and recognition of informal acts of kindness to promote and maintain humanistic patient-care. These measures were described individually rather than as components of a coordinated plan. Few healthcare leaders mentioned plans for organizational or systems changes to promote humanistic clinician-patient relationships. Conclusions Institutional leaders assisted clinicians in dealing with stressful practices in beneficial ways but fell short of envisaging systems approaches that improve practice organization to encourage humanistic care. PRACTICE IMPLICATIONS: To preserve humanistic care requires system changes as well as programs to enhance skills and foster humanistic values and attitudes.
Complex Structures Resulting from Carboxylic Acid Self-Assembly: Comparison of 2-Naphthoic Acid to Quinaldic Acid and 3-Quinoline Carboxylic Acid

Scanning tunneling microscopy was used to study the self-assembly of three molecules on the Au(111) surface: 2-naphthoic acid, quinaldic acid, and 3-quinoline carboxylic acid. All three compounds c...
Synthesis of a bis-(binaphthol)

Abstract A bis-(binaphthol) was prepared by using 3-iodo-1,1′-bi-2-naphthol dimethyl ether and bis(tributylstannyl)acetylene via the Stille reaction.
Modular strategy for the synthesis of functionalized aryl-fused azabicyclo[2.2.2]octanes via radical-mediated cascade cyclization

Abstract A two-step synthesis of rare 2-azabicyclo[2.2.2]octanes is described. N-propargyl amides obtained via Cu(I)-catalyzed three-component coupling, underwent radical-mediated cascade cyclization to afford 5,6-aryl-fused 2-azabicyclo[2.2.2]octanes with arylidene functionality on the two-carbon bridge in 43–62% yields. Phenylidene and 1-naphtylidene derivatives were obtained exclusively as Z diastereomers, whereas electron rich groups in the arylidene substituent afforded product mixtures favoring the Z diastereomer by 2.3:1 M ratio.
General and Efficient Approaches to Fused [1,2-a]Pyrroles and [1,2-a]Indoles

2-[(Benzotriazol-1-yl)methyl]pyrroles 4a−c, and 15a,b and -indoles 23, prepared as previously reported,1,2 were converted into the corresponding fused [1,2-a]pyrroles 8a−c, and 18a,b and fused [1,2-a]indoles 25, 27 by intramolecular cyclizations; the formations of 25 and 27 involve [3 + 2] and [3 + 3] annulations. The benzotriazolyl-CH-ring moieties of intermediates 8a,b, 18a,b, 25, and 27 were further elaborated: (i) acylation of 8a and subsequent reduction and elimination promoted by LiAlH4 to give product 6; (ii) nucleophilic displacements of the benzotriazolyl moiety with NaCN, NaSPh, and Grignard reagents to afford compounds 9, 11, 12, 20, 29, and 32, respectively; (iii) base-assisted eliminations of benzotriazole from 8b and 18a to form the unsaturated fused [1,2-a]pyrroles 10 and 17; (iv) reactions of 18b and 25 with α,β-unsaturated ketone and aldehyde followed by acid-assisted elimination of the benzotriazolyl group to yield tricyclic compound 21 and product 31; and (v) Lewis acid promoted dimeri...
OLIVER: A Tool for Visual Data Analysis on Longitudinal Plant Phenomics Data

There is a critical unmet need for new tools to analyze and understand “big data” in the biological sciences where breakthroughs come from connecting massive genomics data with complex phenomics data. By integrating instant data visualization and statistical hypothesis testing, we have developed a new tool called OLIVER for phenomics visual data analysis with a unique function that any user adjustment will trigger realtime display updates for any affected elements in the workspace. By visualizing and analyzing omics data with OLIVER, biomedical researchers can quickly generate hypotheses and then test their thoughts within the same tool, leading to efficient knowledge discovery from complex, multi-dimensional biological data. The practice of OLIVER on multiple plant phenotyping experiments has shown that OLIVER can facilitate scientific discoveries. In the use case of OLIVER for large-scale plant phenotyping, a quick visualization identified emerging phenomena that are highly transient and heterogeneous. The unique circular heat map with false-color plant images also indicates that such emerging phenomena appear in different leaves under different conditions, suggesting that such previously unseen processes are critical for plant responses to dynamic environments.
Calix[4]arenes with siloxanes bridging opposite rings.

Formula chem. Several C-silylated (allyldimethylsilyl) calixarenes (1, 14, and 18) were treated with commercial TBAF in THF, giving the novel calixarenes 2, 15, and 19, in which the opposite rings were bridged by a Si-0-Si siloxane group. Compound 19 and the derived phenol 20 (as well as the dibromocalixarene precursor 17) were mixtures of cone and partial cone conformations according to NMR, while 2 and 15 (as well as 14 and the cone components of 17, 19, and 20) were in flattened cone conformations.
Large scale synthesis of dysprosium and neodymium diiodides

DyI(2) and NdI(2), which may become useful reagents in organic synthesis, can be prepared in up to 50 g quantities in a few hours without using welded tantalum tubes or temperatures over 1000 degrees C by direct reaction of the metal and iodine.
Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines.

The American College of Medical Genetics and American College of Pathologists (ACMG/AMP) variant classification guidelines for clinical reporting are widely used in diagnostic laboratories for variant interpretation. The ACMG/AMP guidelines recommend complete concordance of predictions among all in silico algorithms used without specifying the number or types of algorithms. The subjective nature of this recommendation contributes to discordance of variant classification among clinical laboratories and prevents definitive classification of variants. Using 14,819 benign or pathogenic missense variants from the ClinVar database, we compared performance of 25 algorithms across datasets differing in distinct biological and technical variables. There was wide variability in concordance among different combinations of algorithms with particularly low concordance for benign variants. We also identify a previously unreported source of error in variant interpretation (false concordance) where concordant in silico predictions are opposite to the evidence provided by other sources. We identified recently developed algorithms with high predictive power and robust to variables such as disease mechanism, gene constraint, and mode of inheritance, although poorer performing algorithms are more frequently used based on review of the clinical genetics literature (2011–2017). Our analyses identify algorithms with high performance characteristics independent of underlying disease mechanisms. We describe combinations of algorithms with increased concordance that should improve in silico algorithm usage during assessment of clinically relevant variants using the ACMG/AMP guidelines.
Ring Fragmentation of Benzotriazol-1-yl Carbanions

The title carbanions 1 are shown to lose nitrogen to afford ortho-carbiminophenyl anions 4 which can be protonated by inter- or intramolecular proton transfer or react inter- or intramolecularly with other types of electrophilic center.
Catalysis of highly stereoselective Mannich-type reactions of ketones with α-imino esters by a pyrrolidine-sulfonamide. Synthesis of unnatural α-amino acids

The novel pyrrolidine-sulfonamide I has been prepared and used successfully to catalyze Mannich-type reactions between ketones and α-imino esters. The process is used to efficiently synthesize functionalized α-amino acid derivatives with excellent levels of regio-, diastereo-, and enantio-selectivity.
Myopic control of neural dynamics

Manipulating the dynamics of neural systems through targeted stimulation is a frontier of research and clinical neuroscience; however, the control schemes considered for neural systems are mismatched for the unique needs of manipulating neural dynamics. An appropriate control method should respect the variability in neural systems, incorporating moment to moment "input" to the neural dynamics and behaving based on the current neural state, irrespective of the past trajectory. We propose such a controller under a nonlinear state-space feedback framework that steers one dynamical system to function as through it were another dynamical system entirely. This "myopic" controller is formulated through a novel variant of a model reference control cost that manipulates dynamics in a short-sighted manner that only sets a target trajectory of a single time step into the future (hence its myopic nature), which omits the need to pre-calculate a rigid and computationally costly neural feedback control solution. To demonstrate the breadth of this control's utility, two examples with distinctly different applications in neuroscience are studied. First, we show the myopic control's utility to probe the causal link between dynamics and behavior for cognitive processes by transforming a winner-take-all decision-making system to operate as a robust neural integrator of evidence. Second, an unhealthy motor-like system containing an unwanted beta-oscillation spiral attractor is controlled to function as a healthy motor system, a relevant clinical example for neurological disorders.
Synthesis and biological studies of novel nucleoside phosphoramidate prodrugs.

A novel approach to the intracellular delivery of nucleotides using phosphoramidate-based prodrugs is described. Specifically, we have developed phosphoramidate prodrugs of the anticancer nucleotide 5-fluoro-2‘-deoxyuridine-5‘monophosphate (FdUMP). These phosphoramidate prodrugs contain an ester group that undergoes intracellular activation liberating phosphoramidate anion, which undergoes spontaneous cyclization and P−N bond cleavage to yield the nucleoside monophosphate quantitatively. In vitro evaluation of 5-fluoro-2‘-deoxyuridine phosphoramidate prodrugs 2a and 3b against L1210 mouse leukemia cells show potent inhibition of cell growth (IC50 0.5−3 nM). Cell-based thymidylate synthase inhibition studies show that, in contrast to FUdR, the nitrofuran compound 2a is of comparable potency in wild type vs thymidine kinase deficient LM cells. This result indicates that the activation of this novel prodrug occurs via the proposed mechanism of intracellular delivery. However, naphthoquinone 3b has an IC50 va...
Pd-Catalyzed C4-Olefination of Oxazoles via C–H Bond Activation: Divergent Synthesis of Functionalized Amino Alcohol and Amino Acid Derivatives

A Pd-catalyzed C4-olefination of oxazoles via C–H bond activation under mild conditions was achieved. The reaction was shown to be general over a range of substrates. New protocols for the divergent transformation of these products to provide functionalized amino alcohol and amino acid derivatives have also been established.
The preparation of aryl 1‐(2,6‐dimethylphenyl)‐2‐phenyl‐4‐trifluoromethyl‐5‐imidazolyl sulfides and sulfones

A series of aryl 1-(2,6-dimethylphenyl)-2-phenyl-4-trifluoromethyl-5- imidazolyl sulfides was prepared by displacement of fluoride from the 5-position of 1-(2,6-dimethylphenyl)2-phenyl-4-trifluoromethyl-5-fluo- roimidazole by substituted thiophenols and by benzyl mercaptan. This displacement reaction occurs much more slowly than the corresponding previously described reactions of 4-trifluoromethyl-5-fluorothiazoles and -oxazoles. Several solvent-base pairs were examined; the reaction was found to work best when dimethyl sulfoxide was used as the solvent and diazabicycloundecene as the base. The sulfides were oxidized to sulfones by treatment with hydrogen peroxide in acetic acid
Microwave-assisted solvothermal synthesis of spinel AV2O4 (M = Mg, Mn, Fe, and Co).

Lower-valent vanadium oxide spinels AV2O4 (A = Mg, Mn, Fe, and Co) consisting of A2+ and V3+ ions have been synthesized by a low-temperature microwave-assisted solvothermal (MW-ST) synthesis process in a tetraethylene glycol (TEG) medium. The oxides are formed within a short reaction time of 30 min at 300 °C. Subsequent postheat treatment of the oxides at elevated temperatures in inert or reducing atmospheres results in an instability of the spinel phase, especially CoV2O4 due to the ease of formation of metallic Co, demonstrating the advantage of the low-temperature MW-ST process in accessing these oxides. This MW-ST synthesis approach is attractive for synthesizing other lower-valent transition-metal oxides that are otherwise difficult to obtain by conventional synthesis methods and for subsequent study of their unique physical and chemical properties.
Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast

The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) protects genome integrity by restoring ligatable 5'-phosphate and 3'-hydroxyl termini at single-strand breaks (SSBs). In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR) of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ) cells of Schizosaccharomyces pombe. Here, we report that pnk1Δ cells have enhanced requirements for Rad3 (ATR/Mec1) and Chk1 checkpoint kinases, and the multi-BRCT domain protein Brc1 that binds phospho-histone H2A (γH2A) at damaged replication forks. The viability of pnk1Δ cells depends on Mre11 and Ctp1 (CtIP/Sae2) double-strand break (DSB) resection proteins, Rad52 DNA strand annealing protein, Mus81-Eme1 Holliday junction resolvase, and Rqh1 (BLM/WRN/Sgs1) DNA helicase. Coupled with increased sister chromatid recombination and Rad52 repair foci in pnk1Δ cells, these findings indicate that lingering SSBs in pnk1Δ cells trigger Rad51-independent homology-directed repair of collapsed replication forks. From these data, we propose models for HDR-mediated tolerance of persistent SSBs with 3' phosphate in pnk1Δ cells.
Balancing sensitivity and specificity in distinguishing TCR groups by CDR sequence similarity

Repertoire sequencing is enabling deep explorations into the cellular immune response, including the characterization of commonalities and differences among T cell receptor (TCR) repertoires from different individuals, pathologies, and antigen specificities. In seeking to understand the generality of patterns observed in different groups of TCRs, it is necessary to balance how well each pattern represents the diversity among TCRs from one group (sensitivity) vs. how many TCRs from other groups it also represents (specificity). The variable complementarity determining regions (CDRs), particularly the third CDRs (CDR3s) interact with major histocompatibility complex (MHC)-presented epitopes from putative antigens, and thus encode the determinants of recognition. We here systematically characterize the predictive power that can be obtained from CDR3 sequences, using representative, readily interpretable methods for evaluating CDR sequence similarity and then clustering and classifying sequences based on similarity. An initial analysis of CDR3s of known structure, clustered by structural similarity, helps calibrate the limits of sequence diversity among CDRs that might have a common mode of interaction with presented epitopes. Subsequent analyses demonstrate that this same range of sequence similarity strikes a favorable specificity/sensitivity balance in distinguishing twins from non-twins based on overall CDR3 repertoires, classifying CDR3 repertoires by antigen specificity, and distinguishing general pathologies. We conclude that within a fairly broad range of sequence similarity, matching CDR3 sequences are likely to share specificities.
Tracking Multiple Genomic Elements Using Correlative CRISPR Imaging and Sequential DNA FISH

Live imaging of genome has offered important insights into the dynamics of the genome organization and gene expression. The demand to image simultaneously multiple genomic loci has prompted a flurry of exciting advances in multicolor CRISPR imaging, although color-based multiplexing is limited by the need for spectrally distinct fluorophores. Here we introduce an approach to achieve highly multiplexed live recording via correlative CRISPR imaging and sequential DNA fluorescence in situ hybridization (FISH). This approach first performs one-color live imaging of multiple genomic loci and then uses sequential rounds of DNA FISH to determine the loci identity. We have optimized the FISH protocol so that each round is complete in 1 min, demonstrating the identification of seven genomic elements and the capability to sustain reversible staining and washing for up to 20 rounds. We have also developed a correlation-based algorithm to faithfully register live and FISH images. Our approach keeps the rest of the color palette open to image other cellular phenomena of interest, as demonstrated by our simultaneous live imaging of genomic loci together with a cell cycle reporter. Furthermore, the algorithm to register faithfully between live and fixed imaging is directly transferrable to other systems such as multiplex RNA imaging with RNA-FISH and multiplex protein imaging with antibody-staining.
Dichloroketene-induced cyclizations of vinyl sulfilimines: application of the method in the synthesis of (+/-)-desoxyeseroline.

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 °C to yield thioalkyl-substituted γ-lactams. The overall process involves nucleophil...
The influence of lymphoid reconstitution kinetics on clinical outcomes in allogeneic stem cell transplantation.

Lymphoid recovery following myeloablative stem cell transplantation (SCT) displays a logistic pattern of exponential growth followed by a plateau. Within this logistic framework, lymphoid recovery is characterized by the parameters R (slope of ascent), a (time of maximal rate of ascent) and K (plateau), the 'steady-state' lymphocyte count. A retrospective analysis of allogeneic SCT performed from 2008 to 2013 was undertaken to compare lymphoid recovery and clinical outcomes in 131 patients with acute myelogenous leukemia, acute lymphocytic leukemia, and myelodysplastic syndromes. Using Prism software, a logistic curve was successfully fit to the absolute lymphocyte count recovery in all patients. Patients were classified according to the magnitude and rate of lymphoid recovery; pattern A achieved an absolute lymphocyte counts (ALC) of >1000/μL by day 45, pattern B an ALC 500 < x < 1000/μL, and pattern C an ALC <500/μL. Pattern A was characterized by a higher mean K (p < .0001) compared with patterns B and C. Patients with patterns B and C were more likely to have mixed T cell chimerism at 90 d following SCT (p = .01). There was a trend towards improved survival (and relapse-free survival) in those with pattern A and B at 1 year compared to pattern C (p = .073). There was no difference in cGVHD (p = .42) or relapse (p = .45) between pattern types. Cytomegalovirus (CMV), aGVHD, and all relapse were heralded by deviation from logistic behavior. Pattern C patients were more likely to require donor lymphocyte infusion (DLI) (p = .017). Weaning of tacrolimus post-transplant was associated with a second, separate logistic expansion in some patients. This study demonstrated that lymphoid reconstitution follows a prototypical logistic recovery and that pattern observed correlates with T cell chimerism and need for DLI, and may influence survival.
HIGHLY ENANTIOSELECTIVE AND REGIOSELECTIVE CATALYTIC DIHYDROXYLATION OF HOMOALLYLIC ALCOHOL DERIVATIVES

Abstract The catalytic dihydroxylation of p-methoxyphenyl ethers of various homoallylic alcohols proceeds with excellent enantioselectivity and in the case of diolefins with regioselectivity due to the favorable influence of the aryl ether moiety, as predicted from a previously proposed transition-state model.
Enantiomerically Enriched α-Methyl Amino Acids. Use of an Acyclic, Chiral Alanine-Derived Dianion with a High Diastereofacial Bias

Hindered esters derived from N-benzoylalanine and the following chiral alcohols have been synthesized: (1) (-)-isopinocampheol; (2) (-)-trans-2-phenylcyclohexanol and (3) (-)-8-phenylmenthol. Sequential treatment of these esters with LDA (1.2 equiv.) and n-butyllithium (2.4 equiv.) at -78°C in THF generates the corresponding chiral dianions. Alkylation of each of these with benzyl bromide reveals that only the (-)-8-phenylmenthyl auxiliary confers a high diastereofacial bias upon its derivative dianion. In fact, that dianion (6) consistently displays diastereomeric ratios in the range of 89:11 to 94:6 for alkylations with a spectrum of nine alkyl halides. If one recrystallization step is included, a single diastereomeric product may be obtained, as is demonstrated for the benzylation of 6. Of particular note, the alkylation with 3,4-bis(tert-butyldimethylsilyloxy)benzyl bromide (18) (94:6 diast. ratio, 72% yield) constitutes a formal synthesis of the clinically important antihypertensive (S)-α-methyl-DOPA (Aldomet), in enantiomerically enriched from. In all cases studied, yields are markedly improved, yet diastereoselectivities unchanged, by the addition of 10% HMPA to the reaction milieu. The (-)-8-phenylmenthol chiral auxiliary is conveniently recovered via ester cleavage with KO2/18-crown-6, following alkylation. Complete deprotection affords enantiomerically enriched (S)-α-methyl amino acids, in all cases examined, indicating that dianion 6 displays a substantial bias in favor of si face alkylation. This sense of diastereoselection is consistent with a chain-extended, internal chelate model for the reactive conformation of the dianion.
Palladium-catalyzed highly diastereoselective cyclic carbopalladation-carbonylative esterification tandem reaction of iododienes and iodoarylalkenes.

[formula: see text] Pd-catalyzed reaction of iododienes and iodoarylalkenes represented by 1, 8, and 10 under 1 atm of CO and a small amount of O2 in the presence of a base, e.g., NEt3, as well as MeOH and H2O in DMF can undergo a highly diastereoselective cyclic carbopalladation-carbonylative esterification tandem process (Type II C-Pd process) to give in high yields the corresponding ester-containing cyclization products, e.g., 2, 9, and 11, in as high as 98% diastereoselectivity.