cssi/SciSciGPT-SciSciNet huggingface dataset:
Sanity Checks for Saliency Maps

Saliency methods have emerged as a popular tool to highlight features in an input deemed relevant for the prediction of a learned model. Several saliency methods have been proposed, often guided by visual appeal on image data. In this work, we propose an actionable methodology to evaluate what kinds of explanations a given method can and cannot provide. We find that reliance, solely, on visual assessment can be misleading. Through extensive experiments we show that some existing saliency methods are independent both of the model and of the data generating process. Consequently, methods that fail the proposed tests are inadequate for tasks that are sensitive to either data or model, such as, finding outliers in the data, explaining the relationship between inputs and outputs that the model learned, and debugging the model. We interpret our findings through an analogy with edge detection in images, a technique that requires neither training data nor model. Theory in the case of a linear model and a single-layer convolutional neural network supports our experimental findings.
Sub-2 Å Ewald curvature corrected structure of an AAV2 capsid variant

Single-particle cryogenic electron microscopy (cryo-EM) provides a powerful methodology for structural biologists, but the resolutions typically attained with experimentally determined structures have lagged behind microscope capabilities. Here, we exploit several technical advances to improve resolution, including per-particle contrast transfer function (CTF) refinement and correction for Ewald sphere curvature. The latter is demonstrated with several experimental samples and should become more standard as resolutions increase or at lower microscope accelerating voltages. The combined application of the described methods to micrographs recorded on a Titan Krios enables structure determination at ~1.86-A resolution of an adeno-associated virus serotype 2 variant (AAV2), an important gene-delivery vehicle. The resulting structural details provide an improved model for understanding the biology of AAV that will guide future vector development for gene therapy.
Persuading Customers to Buy Early: The Value of Personalized Information Provisioning

We study a pricing and information provisioning game between a better-informed seller (such as a retailer) and its customers. The seller is (ex post) better informed about product availability and ...
The impact of body weight on occupational mobility and career development

This paper examines the relationship between individuals' weight and their employment decisions over the life cycle. I estimate a dynamic stochastic model of individuals' annual joint decisions of occupation, hours worked, and schooling. The model allows body weight to affect non-monetary costs, switching costs, and distribution of wages for each occupation; and also allows individuals' employment decisions to affect body weight. I use conditional density estimation to formulate the distributions of wages and body weight evolution. I find that heavier individuals face higher switching costs when transitioning into white collar occupations, earn lower returns to experience in white-collar occupations, and earn lower wages in socially intensive jobs. Simulating the model with estimated parameters, decreased occupational mobility accounts for 10 percent of the obesity wage gap. While contemporaneous wage penalties for body weight are small, the cost over the life cycle is substantial. An exogenous increase in initial body mass by 20 percent leads to a 10 percent decrease in wages over the life course.
The Impact of Industry Consolidation on Government Procurement: Evidence from Department of Defense Contracting

Abstract We study the relationship between market structure and public procurement outcomes. In particular, we ask whether and to what extent consolidation-driven increases in industry concentration affect the way in which the government procures its goods and services. We focus on the defense industry, by far the largest contributor to federal procurement spending in the U.S. This industry experienced a sharp increase in the level of concentration during the 1990s, driven by a series of large mergers between defense contractors. Using detailed microdata on Department of Defense (DoD) contract awards, we estimate the causal effect of industry concentration on a series of procurement outcomes, leveraging the differential impact of these mergers across product markets. We find that market concentration caused the procurement process to become less competitive, with an increase in the share of spending awarded without competition, or via single-bid solicitations. Increased concentration also induced a shift from the use of fixed-price contracts towards cost-plus contracts. However, we find no evidence that consolidation led to a significant increase in acquisition costs. We infer that the government’s buyer power, especially relevant in this context given the government is often the only purchaser, constrained firms from exercising any additional market power gained by consolidation.
Data Collection, EHRs, and Poverty Determinations:

Collecting and deploying poverty-related data is an important starting point for leveraging data regarding social determinants of health in precision medicine. However, we must rethink how we collect and deploy such data. Current modes of collection yield imprecise data that is unsuited for research. Better data can be collected by cross-referencing other sources such as employers and public benefit programs, and by incentivizing and encouraging patients and providers to provide more accurate information. Data thus collected can be used to provide appropriate individual-level clinical and non-clinical care, and to systematically determine what share of social resources healthcare should consume.
Genetic Variation for Ontogenetic Shifts in Metabolism Underlies Physiological Homeostasis in Drosophila

Organismal physiology emerges from metabolic pathways and subcellular structures like the mitochondria that can vary across development and among individuals. Here we tested whether genetic variation at one level of physiology can be buffered at higher biological levels of organization during development by the inherent capacity for homeostasis in physiological systems. We found that the fundamental scaling relationship between mass and metabolic rate, as well as the oxidative capacity per mitochondria, changed significantly across development in the fruit fly Drosophila . However, mitochondrial respiration rate was maintained at similar levels across development. Furthermore, larvae clustered into two types-those that switched to aerobic, mitochondrial ATP production before the second instar and those that relied on anaerobic, glycolytic production of ATP through the second instar. Despite genetic variation for the timing of this metabolic shift, metabolic rate in second-instar larvae was more robust to genetic variation than was the metabolic rate of other instars. We found that larvae with a mitochondrial-nuclear incompatibility that disrupts mitochondrial function had increased aerobic capacity and relied more on anaerobic ATP production throughout development relative to larvae from wild-type strains. By taking advantage of both ways of making ATP, larvae with this mitochondrial-nuclear incompatibility maintained mitochondrial respiratory capacity, but also had higher levels of whole-body reactive oxygen species and decreased mitochondrial membrane potential, potentially as a physiological defense mechanism. Thus, genetic defects in core physiology can be buffered at the organismal level via physiological plasticity and natural populations may harbor genetic variation for distinct metabolic strategies in development that generate similar organismal outcomes.
Plant-Based Diets in CKD.

The US Department of Agriculture, the US Department of Health and Human Services, and the National Kidney Foundation recommend plant-based diets, such as the Dietary Approaches to Stop Hypertension (DASH) diet, which are high in fiber; are low in saturated fat and processed meats; contain sources of
Manifold splines

Constructing splines whose parametric domain is an arbitrary manifold and effectively computing such splines in real-world applications are of fundamental importance in solid and shape modeling, geometric design, graphics, etc. This paper presents a general theoretical and computational framework, in which spline surfaces defined over planar domains can be systematically extended to manifold domains with arbitrary topology with or without boundaries. We study the affine structure of domain manifolds in depth and prove that the existence of manifold splines is equivalent to the existence of a manifold's affine atlas. Based on our theoretical breakthrough, we also develop a set of practical algorithms to generalize triangular B-spline surfaces from planar domains to manifold domains. We choose triangular B-splines mainly because of its generality and many of its attractive properties. As a result, our new spline surface defined over any manifold is a piecewise polynomial surface with high parametric continuity without the need for any patching and/or trimming operations. Through our experiments, we hope to demonstrate that our novel manifold splines are both powerful and efficient in modeling arbitrarily complicated geometry and representing continuously varying physical quantities defined over shapes of arbitrary topology.
Production of X ( 3872 ) accompanied by a pion in B meson decay

If the $X(3872)$ is a weakly bound charm-meson molecule, it can be produced by the creation of ${D}^{*0}{\overline{D}}^{0}$ or ${D}^{0}{\overline{D}}^{*0}$ at short distances followed by the formation of the bound state from the charm-meson pairs. It can also be produced by the creation of ${D}^{*}{\overline{D}}^{*}$ at short distances followed by the rescattering of the charm mesons into $X\ensuremath{\pi}$. We use results of a previous isospin analysis of $B$ meson decays into $K{D}^{(*)}{\overline{D}}^{(*)}$ to estimate the short-distance amplitudes for creating ${D}^{*}{\overline{D}}^{*}$. We use an effective field theory for charm mesons and pions called XEFT to calculate the amplitudes for rescattering of ${D}^{*}{\overline{D}}^{*}$ into $X\ensuremath{\pi}$ with small relative momentum. The $X\ensuremath{\pi}$ invariant mass distribution is predicted to have a narrow peak near the ${D}^{*}{\overline{D}}^{*}$ threshold from a charm-meson triangle singularity. We estimate the branching fractions into the peak from the triangle singularity for the decays ${B}^{0}\ensuremath{\rightarrow}{K}^{+}X{\ensuremath{\pi}}^{\ensuremath{-}}$ and ${B}^{+}\ensuremath{\rightarrow}{K}^{0}X{\ensuremath{\pi}}^{+}$.
Deep Learning for Predicting Dynamic Uncertain Opinions in Network Data

Subjective Logic (SL) is one of well-known belief models that can explicitly deal with uncertain opinions and infer unknown opinions based on a rich set of operators of fusing multiple opinions. Due to high simplicity and applicability, SL has been substantially applied in a variety of decision making in the area of cybersecurity, opinion models, trust models, and/or social network analysis. However, SL and its variants have exposed limitations in predicting uncertain opinions in real-world dynamic network data mainly in three-fold: (1) a lack of scalability to deal with a large-scale network; (2) limited capability to handle heterogeneous topological and temporal dependencies among node-level opinions; and (3) a high sensitivity with conflicting evidence that may generate counterintuitive opinions derived from the evidence. In this work, we proposed a novel deep learning (DL)-based dynamic opinion inference model while node-level opinions are still formalized based on SL meaning that an opinion has a dimension of uncertainty in addition to belief and disbelief in a binomial opinion (i.e., agree or disagree). The proposed DL-based dynamic opinion inference model overcomes the above three limitations by considering the following: (1) state-of-the-art DL techniques, such as the Graph Convolutional Network (GCN) and the Gated Recurrent Units (GRU), for modeling the topological and temporal heterogeneous dependency information of a given dynamic network; (2) modeling conflicting opinions based on robust statistics; and (3) a highly scalable inference algorithm to predict dynamic, uncertain opinions in a linear computation time. We validated the outperformance of our proposed DL-based algorithm (i.e., GCN-GRU-opinion model) via extensive comparative performance analysis based on a real-world dataset.
High-resolution cryo-EM structures of the E. coli hemolysin ClyA oligomers.

Pore-forming proteins (PFPs) represent a functionally important protein family, that are found in organisms from viruses to humans. As a major branch of PFPs, bacteria pore-forming toxins (PFTs) permeabilize membranes and usually cause the death of target cells. E. coli hemolysin ClyA is the first member with the pore complex structure solved among α-PFTs, employing α-helices as transmembrane elements. ClyA is proposed to form pores composed of various numbers of protomers. With high-resolution cryo-EM structures, we observe that ClyA pore complexes can exist as newly confirmed oligomers of a tridecamer and a tetradecamer, at estimated resolutions of 3.2 A and 4.3 A, respectively. The 2.8 A cryo-EM structure of a dodecamer dramatically improves the existing structural model. Structural analysis indicates that protomers from distinct oligomers resemble each other and neighboring protomers adopt a conserved interaction mode. We also show a stabilized intermediate state of ClyA during the transition process from soluble monomers to pore complexes. Unexpectedly, even without the formation of mature pore complexes, ClyA can permeabilize membranes and allow leakage of particles less than ~400 Daltons. In addition, we are the first to show that ClyA forms pore complexes in the presence of cholesterol within artificial liposomes. These findings provide new mechanistic insights into the dynamic process of pore assembly for the prototypical α-PFT ClyA.
The Role of Gatekeepers in Capital Markets

Gatekeepers in financial markets have the power to provide the institutional stability, fortitude, and direction necessary for the development and the smooth functioning of capital markets. At the same time, they are often motivated by their own private incentives. This along with the tradeoffs they face, and the at‐times unintended consequences of the regulations they propose and enforce, can undermine their effectiveness. A thorough understanding of gatekeepers and their roles can thus illuminate academics, the financial community, and regulators on how such gatekeepers can be the most effective and generate the greatest benefits for capital markets. Since gatekeeping roles and the literature they have inspired encompass a wide array of institutions and agencies, our overview concentrates on those that the conference papers appearing in this volume focus on. We conclude that collectively, the papers contribute to significant progress, and point out some crucial areas that call for further investigation and offer opportunities for future research.
Exponential ergodicity and convergence for generalized reflected Brownian motion

In this paper, we provide convergence analysis for a class of Brownian queues in tandem by establishing an exponential drift condition. A consequence is uniform exponential ergodicity for these multidimensional diffusions, including the O’Connell–Yor process. A list of open problems is also presented.
Low-latency Speaker-independent Continuous Speech Separation

Speaker independent continuous speech separation (SI-CSS) is a task of converting a continuous audio stream, which may contain overlapping voices of unknown speakers, into a fixed number of continuous signals each of which contains no overlapping speech segment. A separated, or cleaned, version of each utterance is generated from one of SI-CSS’s output channels nondeterministically without being split up and distributed to multiple channels. A typical application scenario is transcribing multi-party conversations, such as meetings, recorded with microphone arrays. The output signals can be simply sent to a speech recognition engine because they do not include speech overlaps. The previous SI-CSS method uses a neural network trained with permutation invariant training and a data-driven beamformer and thus requires much processing latency. This paper proposes a low-latency SI-CSS method whose performance is comparable to that of the previous method in a microphone array-based meeting transcription task. This is achieved (1) by using a new speech separation network architecture combined with a double buffering scheme and (2) by performing enhancement with a set of fixed beamformers followed by a neural post-filter.
Martingale decomposition and approximations for nonlinearly dependent processes

Abstract This paper proposes a new martingale (MG) decomposition (Gordin, 1969; Hall and Heyde, 1980) for a dependent time series under a predictive dependence measure based on Wu (2005). The decomposition produces a generalized version of the Beveridge–Nelson (BN) lemma (Phillips and Solo, 1992) that accommodates many nonlinear time series, such as GARCH models and threshold autoregressive processes, thereby extending the empirical ambit of the original lemma designed for the linear process. Under this extended framework, MG approximations can be constructed for weighted sums of the nonlinear dependent processes and these approximations lead directly to a new central limit theorem whose range of application includes many practical time series models.
Stop explaining black box machine learning models for high stakes decisions and use interpretable models instead

Black box machine learning models are currently being used for high-stakes decision making throughout society, causing problems in healthcare, criminal justice and other domains. Some people hope that creating methods for explaining these black box models will alleviate some of the problems, but trying to explain black box models, rather than creating models that are interpretable in the first place, is likely to perpetuate bad practice and can potentially cause great harm to society. The way forward is to design models that are inherently interpretable. This Perspective clarifies the chasm between explaining black boxes and using inherently interpretable models, outlines several key reasons why explainable black boxes should be avoided in high-stakes decisions, identifies challenges to interpretable machine learning, and provides several example applications where interpretable models could potentially replace black box models in criminal justice, healthcare and computer vision. There has been a recent rise of interest in developing methods for ‘explainable AI’, where models are created to explain how a first ‘black box’ machine learning model arrives at a specific decision. It can be argued that instead efforts should be directed at building inherently interpretable models in the first place, in particular where they are applied in applications that directly affect human lives, such as in healthcare and criminal justice.
Can pre-commitment increase savings deposits? Evidence from a tax-time field experiment

Abstract For many low- and moderate-income (LMI) households in the U.S., the receipt of the tax refund marks one of the few times during the year when they can build savings. We present findings from a large-scale field experiment designed to encourage LMI tax filers to save their tax refund. The experiment tested combinations of behavioral strategies to promote savings including (1) asking filers at the start of tax preparation to pre-commit to saving their refund, and (2) choice architecture manipulations that emphasized directly depositing their refund into savings accounts or savings bond purchases. The four intervention conditions had a positive impact on the rate of refund deposits into savings accounts, increasing the deposit rate between 42% and 64%. However, the intervention conditions had minimal effects on the rate of bond purchases. The primary driver of increased savings deposits was the manipulation of the choice architecture. By comparison, savings pre-commitments had a more modest effect on savings deposits, on average. The impact of a pre-commitment on savings deposits varies over the course of the tax season, however, with early tax filers being much more responsive to pre-commitment than were later tax filers.
Synthesis and Characterization of Cs5P[Mo4O14(OH)]2·2H2O: A New Molybdophosphate Cluster with Face-Sharing MoO6 Octahedra

The new molybdophosphate cluster [P{Mo4O14(OH)}2]5- of the title compound(shown) is made of two molybdate tetramers connected by a phosphate group. Each tetramer is made of two pairs of face-sharin...
Direct crystal formation from micronized bone and lactic acid: The writing on the wall for calcium-containing crystal pathogenesis in osteoarthritis?

Introduction Pathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic. Interestingly, elevated lactic acid and bone erosion are frequently among the comorbidities and clinical features of patients with highest incidence of crystal arthropathies. This work shows that bone particulates (modeling bone erosion) dissolve in lactic acid and directly generate crystals, possibly presenting a mechanism for crystal accumulation in osteoarthritis. Methods and results Micronized human bone (average particle size of 160 μm x 79 μm) completely dissolved in lactic acid in 48 hours, and in synovial fluid with 500 mMol lactic acid in 5 days, generating birefringent rhomboid and rod-shaped crystals. SEM analysis with energy dispersive x-ray spectroscopy of these crystals showed average dimensions of around 2 μm x 40 μm, which contained oxygen, calcium and phosphorous at 8.64:1.85:1. Raman spectroscopy of the generated crystals further showed 910/cm and 1049/cm peaks, aligning with calcium oxalate monohydrate and calcium pyrophosphate, respectively. Conclusions This work shows that lactic acid and micronized mineralized bone together directly generate calcium-containing crystals. These observations may provide insights into the elusive etiology of arthritis with crystal involvement, possibly indicating lactic acid as a clinical target for treatment.
Accurate differential analysis of transcription factor activity from gene expression

Motivation Activity of transcriptional regulators is crucial in elucidating the mechanism of phenotypes. However regulatory activity hypotheses are difficult to experimentally test. Therefore, we need accurate and reliable computational methods for regulator activity inference. There is extensive work in this area, however, current methods have difficulty with one or more of the following: resolving activity of TFs with overlapping regulons, reflecting known regulatory relationships, or flexible modeling of TF activity over the regulon. Results We present Effector and Perturbation Estimation Engine (EPEE), a method for differential analysis of transcription factor (TF) activity from gene expression data. EPEE addresses each of these principal challenges in the field. Firstly, EPEE collectively models all TF activity in a single multivariate model, thereby accounting for the intrinsic coupling among TFs that share targets, which is highly frequent. Secondly, EPEE incorporates context-specific TF-gene regulatory networks and therefore adapts the analysis to each biological context. Finally, EPEE can flexibly reflect different regulatory activity of a single TF among its potential targets. This allows the flexibility to implicitly recover other regulatory influences such as co-activators or repressors. We comparatively validated EPEE in 15 datasets from three well-studied contexts, namely immunology, cancer, and hematopoiesis. We show that addressing the aforementioned challenges enable EPEE to outperform alternative methods and reliably produce accurate results. Availability and implementation https://github.com/Cobanoglu-Lab/EPEE. Supplementary information Supplementary data are available at Bioinformatics online.
Situated learning theory in health professions education research: a scoping review

At a time when cognitive and behavioral theories dominated the landscape of learning theories, Lave and Wenger's situated learning theory (SLT) opened new territory by illuminating social and cultural learning processes. Many researchers and educators in the health professions embraced this theory, but few have considered how SLT has been used and what has been learned or improved through its use in health professions education (HPE). In this scoping review, the authors examine these questions and consider opportunities for future work with SLT in HPE. The authors followed Levac's modified scoping review framework. They conducted a search of CINAHL, ERIC, PubMed, Scopus, and Web of Science for articles referencing SLT or related concepts in HPE between 2006 and 2016. Two reviewers screened all titles and abstracts, then screened full text for inclusion based on substantive treatment of SLT. Two authors extracted, analyzed and synthesized data from the final set of 193 articles. The authors identified two patterns of theory use. One sought an understanding of social learning processes in a specific context. The other aimed to design and/or evaluate interventions associated with communities of practice. These patterns are similar to other literatures (e.g., general education, healthcare, and organizational development) and, according to Lave and Wenger, may reflect confusion about the purpose, stance, and terminology of SLT. The authors discuss their findings in relation to primary source literature and consider opportunities for HPE researchers to employ and contribute to SLT going forward.
Multi-Connection Pattern Analysis: Decoding the representational content of neural communication

The lack of multivariate methods for decoding the representational content of interregional neural communication has left it difficult to know what information is represented in distributed brain circuit interactions. Here we present Multi-Connection Pattern Analysis (MCPA), which works by learning mappings between the activity patterns of the populations as a factor of the information being processed. These maps are used to predict the activity from one neural population based on the activity from the other population. Successful MCPA-based decoding indicates the involvement of distributed computational processing and provides a framework for probing the representational structure of the interaction. Simulations demonstrate the efficacy of MCPA in realistic circumstances. In addition, we demonstrate that MCPA can be applied to different signal modalities to evaluate a variety of hypothesis associated with information coding in neural communications. We apply MCPA to fMRI and human intracranial electrophysiological data to provide a proof-of-concept of the utility of this method for decoding individual natural images and faces in functional connectivity data. We further use a MCPA-based representational similarity analysis to illustrate how MCPA may be used to test computational models of information transfer among regions of the visual processing stream. Thus, MCPA can be used to assess the information represented in the coupled activity of interacting neural circuits and probe the underlying principles of information transformation between regions.
Stereoselective synthesis of dibenzoxapine containing tetrasubstituted exocyclic alkenes via cascade methylboronic acid coupling reactions

A stereoselective method for the preparation of dibenzoxapine containing tetrasubstituted exocyclic E-alkenes has been developed. The key reaction involves an intramolecular cyclocarbopalladation of alkynes to form a vinylpalladium species and subsequently coupling the vinylpalladium with methylboronic acid. The approach provides a straightforward method for the synthesis of tetrasubstituted exocyclic E-alkenes.
Copper-Catalyzed Aminohalogenation Using the 2-NsNCl2/2-NsNHNa Combination as the Nitrogen and Halogen Sources for the Synthesis of anti-Alkyl 3-Chloro-2-(o-nitrobenzenesulfonamido)-3-arylpropionates

New regio- and stereoselective aminohalogenation of cinnamic esters has been developed using the combination of 2-NsNCl2/2-NsNHNa as the nitrogen and chlorine sources and copper(I) triflate as the catalyst. The new procedure provides an efficient synthesis of anti-alkyl 3-chloro-2-(o-nitrobenzenesulfonamido)-3-phenylpropionate derivatives. Nine examples are presented with good yields (62−82%) and stereoselectivity ((5:1)−(30:1)).
10‐Thia‐mesobilirubin‐xiiiα

The 10-thia analog of mesobilirubin-XIIIα, with the central C(10) CH2 group replaced by sulfur (1a) was synthesized by condensation of neoxanthobilirubic acid (3) with sulfur dichloride. Thia-rubin 1a is a brilliant yellow solid, forming bright yellow solutions with uv-visible absorption maximum from 425–440 nm.
Synthesis of Unsymmetrical o-Biphenols and o-Binaphthols via Silicon-Tethered Pd-Catalyzed C−H Arylation

A mild, practical, and efficient method for the synthesis of unsymmetrical o-biphenols (including o-phenol-naphthols and o-binaphthols) has been developed. Unsymmetrical bis-aryloxy silanes, which were readily prepared in a semi-one-pot fashion, underwent the Pd-catalyzed intramolecular arylation followed by a routine TBAF desilylation step to furnish valuable unsymmetrical biphenols without necessity of isolation of seven-membered intermediates. The excellent functional group tolerance allows for synthesis of a variety of functionalized o-biphenols and o-binaphthols from easily available staring materials.
Studies Toward an Asymmetric Synthesis of CP-263,114 and CP-225,917

An enantioselective approach to construction of the complex framework of the CP compounds is presented. The synthesis relies on initial elaboration of the two sidechains. The "upper" appendage was asymmetrically dihydroxylated with both AD-mix reagents in order to lend flexibility to the scheme and provide the necessary handle for evolving the additional stereogenic centers. These fragments were linked to benzoic acid via Birch reduction-alkylation and subsequent cuprate addition. A series of functionalization reactions including dissolving metal reduction, Claisen rearrangement, iodolactonization, regioselective epoxide cleavage-oxidation, and intramolecular Wadsworth-Emmons cyclization took advantage of highly efficient stereocontrol. However, this flexibility was thwarted when deprotonation of a penultimate intermediate failed to be regioselective in the proper direction.
Sequencing cross-metathesis and non-metathesis reactions to rapidly access building blocks for synthesis

The olefin cross-metathesis reaction has been sequenced with four common organic transformations in a one- or two-pot manner to rapidly access useful building blocks. Those reactions are: (1) phosphorus-based olefination (e.g., Wittig and Horner–Wadsworth–Emmons); (2) hydride reduction; (3) Evans propionate aldol reaction; (4) Brown allyl- and Roush crotyl-boration. The products of these reactions include stereodefined 2,4-dienoates, trans allylic alcohols, syn-propionate aldols, and chiral non-racemic homoallylic alcohols, respectively. Many of these intermediates have been carried further to natural products, demonstrating the utility of the methodology.
Hydroboration of Alkene-Containing Hydantoins

A direct hydroboration of alkene-containing hydantoins using diisopinocampheylborane has been developed that can be used to prepare boronated amino acids. The method is successful because boronic acids are stable to the conditions employed for hydrolyzing hydantoins.
Development of a new class of C1-symmetric bisphosphine ligands for rhodium-catalyzed asymmetric hydrogenation

Abstract A new class of C1-symmetric bisphosphine ligands with three hindered quadrants have been obtained through facile synthesis from chiral BINOL derivatives. Their rhodium complexes have exhibited high enantioselectivities (up to 98% ee) in the asymmetric hydrogenation of various unsaturated prochiral olefins, providing an efficient catalytic system for the enantioselective synthesis of chiral amino acids and amines.
An anomalous reaction of 7‐chloro‐2‐hydrazono‐5‐phenyl‐1,2‐dihydro‐3H‐1,4‐benzodiazepine with sodium acetate and 1,1′‐carbonyldiimidazole

The addition of 7-chloro-2-hydrazono-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine 3 to a mixture of sodium acetate and 1,1′-carbonyldiimidazole 1 at room temperature gave, in moderate yields, carbonyl-1,1′-bis[7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ylidene hydrazone] 7 instead of the expected 2-acetylhydrazono-7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine 4.
BORON TRIFLUORIDE MEDIATED, ONE-POT SYNTHESIS OF 3-METHYL-1,2-DIHYDRONAPHTHALENES

(2001). BORON TRIFLUORIDE MEDIATED, ONE-POT SYNTHESIS OF 3-METHYL-1,2-DIHYDRONAPHTHALENES. Organic Preparations and Procedures International: Vol. 33, No. 2, pp. 198-201.
Toward Transition Metal-Catalyzed Carbonylation of Methanol without HI as Copromoter: Catalytic Exocyclic Carbonylation of Cycloimino Esters

Initial studies of a rare exocyclic C−O bond carbonylation are reported. Under the catalysis of Co2(CO)8 in the absence of HI as the copromoter, cycloimino esters are carbonylated to afford N-acyllactams in high yields under relatively mild conditions (100−160 °C and 200−1000 psi). The reaction is interesting because it opens up the possibility of carbonylation of alcohols in the absence of HI.
Synthesis and conjugate addition reactions of N-(β-nitroalkyl)amides

Abstract Nitration of several di- and trisubstituted alkenes with lithium nitrate/TFAA in nitrile solvents afforded N -(β-nitroalkyl)amides in 28–72% yields. Nitration of 1,1-diphenylethene gave 1,1-diphenyl-2-nitroethene in 52% yield instead of the N -(β-nitroalkyl)amide. Reaction of 1-methylcyclohexene using excess lithium nitrate/TFAA in acetonitrile gave a single diastereomer of N -(2,6-dinitro-1-cyclohexyl)acetamide in 55% yield. N -(β-Nitroalkyl)amides underwent diastereoselective Michael addition to a variety of Michael acceptors. Diastereoselectivity is rationalized on the basis of internal hydrogen-bonding within the intermediate nitronate resulting in a strongly-biased Michael donor conformation.
Design and synthesis of ansamycin antibiotics

Abstract Ansamycin antibiotics are a class of microbial metabolites that exhibit an array of biological activities. This review covers the synthetic chemistry and biological activity of benzenic ansamycins from 1989 to 2007. In the first section, synthetic approaches to the C15-benzene ansamycins (geldanamycin and related) are discussed. Access to the C17-benzene ansamycins (or ansatrienins) is disclosed in the second half of this article.
Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease

Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer’s disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer’s disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region. We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging. We confirm the association of two well-established miRNA (miR-132, miR-129) with pathologic AD in our dataset and then further characterize this association in terms of its component neuritic β-amyloid plaques and neurofibrillary tangle pathologies. Additionally, we identify one new miRNA (miR-99) and four lincRNA that are associated with these traits. Many other previously reported associations of microRNA with AD are associated with the confounders quantified in our longitudinal cohort. Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis. Overall, miRNAs play a modest role in human AD, but we observe robust evidence that a small number of miRNAs are responsible for specific alterations in the cortical transcriptome that are associated with AD.
Enantioselective reduction of ketones. Examination of bifunctional ligands

Abstract New bifunctional ligands based on a cis-amino indanol framework have been evaluated in the reduction of prochiral ketones. These reductions proceed with high chemical efficiency and good-to-excellent enantioselectivity using borane and 10 mol% of an oxazaborolidine derived from cis-2-amino indanol ligand containing a 2-sulfonylpyridyl tether attached to the amino group.
Synthesis of 6-aminobenzo[b]naphtho[2,1-d]thiophene

6-Aminobenzo[b]naphtho[2,1-d]thiophene has been prepared by two different routes, one, a one-pot synthesis.
Signatures of selection in the human antibody repertoire: Selective sweeps, competing subclones, and neutral drift

Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the population genetic signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically. We measured the dynamics and genetic diversity of B cell responses in five adults longitudinally before and after influenza vaccination using high-throughput antibody repertoire sequencing. We identified vaccine-responsive B cell lineages that carry signatures of selective sweeps driven by positive selection, and discovered that they often display evidence for selective sweeps favoring multiple subclones. We also found persistent B cell lineages that exhibit stable population dynamics and carry signatures of neutral drift. By exploiting the relationship between B cell fitness and antibody binding affinity, we demonstrate the potential for using phylogenetic approaches to identify antibodies with high binding affinity. This quantitative characterization reveals that antibody repertoires are shaped by an unexpectedly broad spectrum of evolutionary processes and shows how signatures of evolutionary history can be harnessed for antibody discovery and engineering.
A practical and inexpensive ‘convertible’ isonitrile for use in multicomponent reactions

Abstract N - tert -Butylamides are readily converted into the corresponding carboxylic acids by simple nitrosation. The process, which occurs under mild nonaqueous conditions, leaves carboxylic esters untouched and transforms multicomponent reaction products into useful building blocks for further synthetic elaboration.
A highly regioselective reaction of N-fluoropyridinium salts with stabilized sulfur, oxygen, and nitrogen nucleophiles : a convenient route to 2-substituted pyridines

2-Substituted pyridines are efficiently obtained by the reactions of N-fluoropyridinium tetrafluoroborate or triflate with anions derived from benzenethiols, phenols, azoles, cyanamide, and with azide anion. The results are consistent with a nucleophile addition at the position 2 of the N-fluoropyridinium cation as the major reaction pathway.
STRUCTURE-BASED DESIGN OF A NEW CLASS OF PROTEIN KINASE C MODULATORS

Protein kinase C (PKC) is a ubiquitous diacylglycerol (DAG)activated signal transducing enzyme system that is coupled to diverse biological events including regulation of ion channels, neurotransmitter release, growth and differentiation, apoptosis, and neuronal plasticity.1 Apart from diacylglycerol,2 the endogenous activator of PKC, several complex natural products and their analogues such as the phorbol esters, bryostatin, teleocidin, and indolactam V (ILV) can mimic DAG to activate PKC at low concentrations.3-5 Synthesis,6-8 molecular modeling,6,9-11 and structure-activity relationships12,13 of ILV and its analogues have been reported. The available X-ray structure of PKCδ in complex with phorbol 13-acetate10 provides information invaluable to the design of new classes of PKC modulators. This paper presents the first example of the structure-based design, synthesis, and biological activities of certain γ-lactams as novel mimics of ILV.
Illumination pattern design with deep learning for single-shot Fourier ptychographic microscopy

Fourier ptychographic microscopy allows for the collection of images with a high space-bandwidth product at the cost of temporal resolution. In Fourier ptychographic microscopy, the light source of a conventional widefield microscope is replaced with a light-emitting diode (LED) matrix, and multiple images are collected with different LED illumination patterns. From these images, a higher-resolution image can be computationally reconstructed without sacrificing field-of-view. We use deep learning to achieve single-shot imaging without sacrificing the space-bandwidth product, reducing the acquisition time in Fourier ptychographic microscopy by a factor of 69. In our deep learning approach, a training dataset of high-resolution images is used to jointly optimize a single LED illumination pattern with the parameters of a reconstruction algorithm. Our work paves the way for high-throughput imaging in biological studies.
Structure of NaBi3V2O10 and Implications for Ionic Conductivity

The structure of a good oxygen ion conductor of nominal composition NaBi3V2O10 was refined using both single-crystal X-ray and powder neutron diffraction data. The actual composition was found to be Na0.96Bi3.04V2O10.04 for this centric triclinic structure. The oxygen conductivity had previously been attributed to vacancies at one of the oxygen sites. However, we find all oxygen sites to be filled. Instead, it appears that the conductivity results from the 0.04 excess oxygen existing as interstitials.
Suppression of Transposable Elements in Leukemic Stem Cells

Genomic transposable elements (TEs) comprise nearly half of the human genome. The expression of TEs is considered potentially hazardous, as it can lead to insertional mutagenesis and genomic instability. However, recent studies have revealed that TEs are involved in immune-mediated cell clearance. Hypomethylating agents can increase the expression of TEs in cancer cells, inducing ‘viral mimicry’, causing interferon signalling and cancer cell killing. To investigate the role of TEs in the pathogenesis of acute myeloid leukaemia (AML), we studied TE expression in several cell fractions of AML while tracking its development (pre-leukemic haematopoietic stem cells, leukemic stem cells [LSCs], and leukemic blasts). LSCs, which are resistant to chemotherapy and serve as reservoirs for relapse, showed significant suppression of TEs and interferon pathways. Similarly, high-risk cases of myelodysplastic syndrome (MDS) showed far greater suppression of TEs than low-risk cases. We propose TE suppression as a mechanism for immune escape in AML and MDS. Repression of TEs co-occurred with the upregulation of several genes known to modulate TE expression, such as RNA helicases and autophagy genes. Thus, we have identified potential pathways that can be targeted to activate cancer immunogenicity via TEs in AML and MDS.
Synthesis of polynuclear aromatic compounds through net [5+5]-cycloaddition of 2-alkynylarylcarbene complexes and enyne–aldehyde derivatives

Abstract Coupling of o -alkynylphenylcarbene complexes and – o -alkynylheteroarene carboxaldehydes leads to heterocycle annulated phenanthrene derivatives.
Thiazole and Thiophene Analogues of Donor−Acceptor Stilbenes: Molecular Hyperpolarizabilities and Structure−Property Relationships

We calculate the first hyperpolarizability (β) of several thiazole and thiophene analogues of donor−acceptor stilbene compounds using the ZINDO (sum-over-states) formalism. Because of the inherent dipolar nature of thiazole, in which C2 is electron-poor and C5 is electron-rich, the relative orientation of the thiazole subunit in the dipolar chromophore dramatically affects the nonlinear optical properties. In the “mismatched” case, the dipole of the thiazole ring opposes the molecular dipole created by the donor−acceptor substituents, while in the “matched” case, the dipole of the thiazole ring reinforces the molecular dipole. The hyperpolarizability of the “mismatched” monothiazole 2 (βμ = 68 × 10-30 cm5 esu-1) exceeds that of stilbene 1 (βμ = 34 × 10-30 cm5 esu-1) but is smaller than that of monothiophene 4 (βμ = 90 × 10-30 cm5 esu-1). By contrast, the hyperpolarizability of the “matched” monothiazole 3 (βμ = 177 × 10-30 cm5 esu-1) exceeds not only that of the “mismatched” monothiazole 2, but also that ...
Benzylation of 1‐Benzylidene‐3‐Pyrazolidinium Oxides

The benzylation of 1-benzylidene-5-phenyl-3-pyrazolidinium oxide (2a) gives five products including the “head to head” dimer of 2 (7) and the ring-opened 1-benzyl-1-cinnamoylbenzalhydrazone (4a). Similar behavior was also observed with ylides bearing various substituents at the 4 and 5 positions.
Stereoselective tandem 1,4-addition reactions for benzenes: a comparison of Os(II), Re(I), and W(0) systems.

The arene ligand in the complex TpRe(CO)(MeIm)(η2-benzene) (Tp = hydridotris(pyrazolyl)borate; MeIm = N-methylimidazole) undergoes tandem electrophile/nucleophile 1,4-addition reactions. Subsequent oxidative demetalation affords cis-3,6-disubstituted 1,4-cyclohexadienes (46−84%). Common organic electrophiles such as acetals and Michael acceptors were successfully added to the bound benzene to generate η3-benzenium complexes, which then were treated with a silyl ketene acetal, silyl vinyl ether, phenyllithium, or malonate ester to afford 1,4-dialkylated dihydrobenzene complexes. The d6 transition metal analogues TpW(NO)(PMe3)(η2-benzene) and [Os(NH3)5(η2-benzene)]2+ also undergo 1,4-dialkylation reactions, and the relative ability of all three metals to activate arenes is compared.
Readily synthesized novel fluorescent dipyrrinones.

A new, highly fluorescent (φF up to 0.85) rigid anti-Z-dipyrrinone chromophore has been synthesized in high yield in a one-pot reaction by condensing two monopyrroles in the presence of DBU to form the pyrrolo[3,2-f]indolizine-4,6-dione nucleus.
Synthesis of cyclic enamides by intramolecular cyclization of acetylenic amides

Abstract Cyclic enamides 12 of a type useful in the synthesis of naturally occurring chlorins, isobacteriochlorins, and corrins have been prepared by a process involving Nicholas-Schreiber condensation to afford acetylenic amides 13, followed by either n-Bu4NF or LiA1(NHBn)4-catalyzed ring closure.
The Seven Sins of Personal-Data Processing Systems under {GDPR}

In recent years, our society is being plagued by unprecedented levels of privacy and security breaches. To rein in this trend, the European Union, in 2018, introduced a comprehensive legislation called the General Data Protection Regulation (GDPR). In this paper, we review GDPR from a system design perspective, and identify how its regulations conflict with the design, architecture, and operation of modern systems. We illustrate these conflicts via the seven GDPR sins: storing data forever; reusing data indiscriminately; walled gardens and black markets; risk-agnostic data processing; hiding data breaches; making unexplainable decisions; treating security as a secondary goal. Our findings reveal a deep-rooted tussle between GDPR requirements and how modern systems have evolved. We believe that achieving compliance requires comprehensive, grounds up solutions, and anything short would amount to fixing a leaky faucet in a sinking ship.