cssi/SciSciGPT-SciSciNet huggingface dataset:
Dynamic autonomous vehicle fleet operations: Optimization-based strategies to assign AVs to immediate traveler demand requests

Abstract Motivated by the growth of ridesourcing services and the expected advent of fully-autonomous vehicles (AVs), this paper defines, models, and compares assignment strategies for a shared-use AV mobility service (SAMS). Specifically, the paper presents the on-demand SAMS with no shared rides, defined as a fleet of AVs, controlled by a central operator, that provides direct origin-to-destination service to travelers who request rides via a mobile application and expect to be picked up within a few minutes. The underlying operational problem associated with the on-demand SAMS with no shared rides is a sequential (i.e. dynamic or time-dependent) stochastic control problem. The AV fleet operator must assign AVs to open traveler requests in real-time as traveler requests enter the system dynamically and stochastically. As there is likely no optimal policy for this sequential stochastic control problem, this paper presents and compares six AV-traveler assignment strategies (i.e. control policies). An agent-based simulation tool is employed to model the dynamic system of AVs, travelers, and the intelligent SAMS fleet operator, as well as, to compare assignment strategies across various scenarios. The results show that optimization-based AV-traveler assignment strategies, strategies that allow en-route pickup AVs to be diverted to new traveler requests, and strategies that incorporate en-route drop-off AVs in the assignment problem, reduce fleet miles and decrease traveler wait times. The more-sophisticated AV-traveler assignment strategies significantly improve operational efficiency when fleet utilization is high (e.g. during the morning or evening peak); conversely, when fleet utilization is low, simply assigning traveler requests sequentially to the nearest idle AV is comparable to more-advanced strategies. Simulation results also indicate that the spatial distribution of traveler requests significantly impacts the empty fleet miles generated by the on-demand SAMS.
Tverberg Partitions as Weak Epsilon-Nets

We prove a Tverberg-type theorem using the probabilistic method. Given $\varepsilon >0$, we find the smallest number of partitions of a set $X$ in $R^d$ into $r$ parts needed in order to induce at least one Tverberg partition on every subset of $X$ with at least $\varepsilon |X|$ elements. This generalizes known results about Tverberg's theorem with tolerance.
Mapping online child safety in Asia and the Pacific

In today's age, the Internet has become essential for children's education and social development. Yet the very same technologies can expose children to online harm, which can negatively impact their wellâ€ being and safety. These risks are becoming more serious as Internet penetration rises, particularly in emerging countries that have limited resources and capacities to tackle complex issues such as online sexual abuse, cyberbullying, and Internet addiction. As research on the entire range of risks that children are exposed to online is limited, particularly in Asia and the Pacific, this study aims to initiate the process of filling this knowledge gap and proposes a set of policy recommendations to address the challenge of balancing children's online opportunities and risks. A key finding from the study is the need for a multistakeholder and collaborative approach to ensure the online safety of children, which must include children themselves.
Image denoising with generalized Gaussian mixture model patch priors

Patch priors have become an important component of image restoration. A powerful approach in this category of restoration algorithms is the popular expected patch log-likelihood (EPLL) algorithm. E...
The Illusion of Multitasking and Its Positive Effect on Performance

With technological advancements, the desire, ability, and often necessity to multitask are pervasive. Although multitasking refers to the simultaneous execution of multiple tasks, most activities that require active attention cannot actually be done simultaneously. Therefore, whether a certain activity is considered multitasking is often a matter of perception. This article demonstrates the malleability of what people perceive as multitasking, showing that the same activity may or may not be construed as multitasking. Importantly, although engaging in multiple tasks may diminish performance, we found that, holding the activity constant, the mere perception of multitasking in fact improves performance. Across 32 studies (30 of which had performance-based incentives) containing a total of 8,242 participants, we found that individuals who perceived an activity as multitasking were more engaged and consequently outperformed those who perceived that same activity as single tasking.
Complex patterns of sex-biased demography in canines.

The demographic history of dogs is complex, involving multiple bottlenecks, admixture events and artificial selection. However, existing genetic studies have not explored variance in the number of ...
Role of disordered bipolar complexions on the sulfur embrittlement of nickel general grain boundaries

Minor impurities can cause catastrophic fracture of normally ductile metals. Here, a classic example is represented by the sulfur embrittlement of nickel, whose atomic-level mechanism has puzzled researchers for nearly a century. In this study, coupled aberration-corrected electron microscopy and semi-grand-canonical-ensemble atomistic simulation reveal, unexpectedly, the universal formation of amorphous-like and bilayer-like facets at the same general grain boundaries. Challenging the traditional view, the orientation of the lower-Miller-index grain surface, instead of the misorientation, dictates the interfacial structure. We also find partial bipolar structural orders in both amorphous-like and bilayer-like complexions (a.k.a. thermodynamically two-dimensional interfacial phases), which cause brittle intergranular fracture. Such bipolar, yet largely disordered, complexions can exist in and affect the properties of various other materials. Beyond the embrittlement mechanism, this study provides deeper insight to better understand abnormal grain growth in sulfur-doped Ni, and generally enriches our fundamental understanding of performance-limiting and more disordered interfaces.
Evolution of Modern Business Cycle Models: Accounting for the Great Recession

Modern business cycle theory focuses on the study of dynamic stochastic general equilibrium (DSGE) models that generate aggregate fluctuations similar to those experienced by actual economies. We discuss how these modern business cycle models have evolved across three generations, from their roots in the early real business cycle models of the late 1970s through the turmoil of the Great Recession four decades later. The first generation models were real (that is, without a monetary sector) business cycle models that primarily explored whether a small number of shocks, often one or two, could generate fluctuations similar to those observed in aggregate variables such as output, consumption, investment, and hours. These basic models disciplined their key parameters with micro evidence and were remarkably successful in matching these aggregate variables. A second generation of these models incorporated frictions such as sticky prices and wages; these models were primarily developed to be used in central banks for short-term forecasting purposes and for performing counterfactual policy experiments. A third generation of business cycle models incorporate the rich heterogeneity of patterns from the micro data. A defining characteristic of these models is not the heterogeneity among model agents they accommodate nor the micro-level evidence they rely on (although both are common), but rather the insistence that any new parameters or feature included be explicitly disciplined by direct evidence. We show how two versions of this latest generation of modern business cycle models, which are real business cycle models with frictions in labor and financial markets, can account, respectively, for the aggregate and the cross-regional fluctuations observed in the United States during the Great Recession.
Improving simple models with confidence profiles

In this paper, we propose a new method called ProfWeight for transferring information from a pre-trained deep neural network that has a high test accuracy to a simpler interpretable model or a very shallow network of low complexity and a priori low test accuracy. We are motivated by applications in interpretability and model deployment in severely memory constrained environments (like sensors). Our method uses linear probes to generate confidence scores through flattened intermediate representations. Our transfer method involves a theoretically justified weighting of samples during the training of the simple model using confidence scores of these intermediate layers. The value of our method is first demonstrated on CIFAR-10, where our weighting method significantly improves (3-4%) networks with only a fraction of the number of Resnet blocks of a complex Resnet model. We further demonstrate operationally significant results on a real manufacturing problem, where we dramatically increase the test accuracy of a CART model (the domain standard) by roughly 13%.
Using Deep Neural Networks to Translate Multi-lingual Threat Intelligence

The multilingual nature of the Internet increases complications in the cybersecurity community’s ongoing efforts to strategically mine threat intelligence from OSINT data on the web. OSINT sources such as social media, blogs, and dark web vulnerability markets exist in diverse languages and hinder security analysts, who are unable to draw conclusions from intelligence in languages they don’t understand. Although third party translation engines are growing stronger, they are unsuited for private security environments. First, sensitive intelligence is not a permitted input to third party engines due to privacy and confidentiality policies. In addition, third party engines produce generalized translations that tend to lack exclusive cybersecurity terminology. In this paper, we address these issues and describe our system that enables threat intelligence understanding across unfamiliar languages. We create a neural network based system that takes in cybersecurity data in a different language and outputs the respective English translation. The English translation can then be understood by an analyst, and can also serve as input to an AI based cyber-defense system that can take mitigative action. As a proof of concept, we have created a pipeline which takes Russian threats and generates its corresponding English, RDF, and vectorized representations. Our network optimizes translations on specifically, cybersecurity data.
Mechanism behind the Unusually High Conductivities of High Concentrated Sodium Ion Glyme-Based Electrolytes

New highly concentrated electrolytes based on ether solvents were developed for sodium electrochemical cells. The investigated electrolytes use sodium triflate and glycol diether oligomers of different length to form the electrolyte. These electrolytes present conductivities that increase as a function of concentration even when the electrolyte is composed of a majority of ion pairs and aggregates. Correlation analysis between the electrolyte speciation and conductivity suggests the presence of two distinct mechanisms of charge transport, namely a traditional vehicular mechanism based on the diffusion of free ions and a hopping mechanism involving the making and breaking of ion-pairs and/or aggregates. The former mechanism represents the charge transport of glyme with 3 or 4 units, while the latter is observed in electrolytes composed of short chains, i.e., 1 or 2 units. The proposed mechanism of transport is corroborated via molecular dynamics simulations. In addition, our experiments demonstrate that th...
Structure Reveals a Mechanism of CRISPR-RNA-Guided Nuclease Recruitment and Anti-CRISPR Viral Mimicry.

Summary Bacteria and archaea have evolved sophisticated adaptive immune systems that rely on CRISPR RNA (crRNA)-guided detection and nuclease-mediated elimination of invading nucleic acids. Here, we present the cryo-electron microscopy (cryo-EM) structure of the type I-F crRNA-guided surveillance complex (Csy complex) from Pseudomonas aeruginosa bound to a double-stranded DNA target. Comparison of this structure to previously determined structures of this complex reveals a ∼180-degree rotation of the C-terminal helical bundle on the “large” Cas8f subunit. We show that the double-stranded DNA (dsDNA)-induced conformational change in Cas8f exposes a Cas2/3 “nuclease recruitment helix” that is structurally homologous to a virally encoded anti-CRISPR protein (AcrIF3). Structural homology between Cas8f and AcrIF3 suggests that AcrIF3 is a mimic of the Cas8f nuclease recruitment helix.
SelSMaP: A Selective Stride Masking Prefetching Scheme

Data prefetching, which intelligently loads data closer to the processor before demands, is a popular cache performance optimization technique to address the increasing processor-memory performance gap. Although prefetching concepts have been proposed for decades, sophisticated system architecture and emerging applications introduce new challenges. Large instruction windows coupled with out-of-order execution makes the program data access sequence distorted from a cache perspective. Furthermore, big data applications stress memory subsystems heavily with their large working set sizes and complex data access patterns. To address such challenges, this work proposes a high-performance hardware prefetching scheme, SelSMaP. SelSMaP is able to detect both regular and nonuniform stride patterns by taking the minimum observed address offset (called a reference stride) as a heuristic. A stride masking is generated according to the reference stride and is to filter out history accesses whose pattern can be rephrased as uniform stride accesses. Prefetching decision and prefetch degree are determined based on the masking outcome. As SelSMaP prediction logic does not rely on the chronological order of data accesses or program counter information, it is able to unveil the effect of out-of-order execution and compiler optimization. We evaluated SelSMaP with CloudSuite workloads and SPEC CPU2006 benchmarks. SelSMaP achieves an average CloudSuite performance improvement of 30% over nonprefetching systems. With one to two orders of magnitude less storage and much less functional logic, SelSMaP outperforms the highest-performing prefetcher by 8.6% in CloudSuite workloads.
Muller’s Ratchet and Ribosome Degeneration in the Obligate Intracellular Parasites Microsporidia

Microsporidia are fungi-like parasites that have the smallest known eukaryotic genome, and for that reason they are used as a model to study the phenomenon of genome decay in parasitic forms of life. Similar to other intracellular parasites that reproduce asexually in an environment with alleviated natural selection, Microsporidia experience continuous genome decay that is driven by Muller's ratchet-an evolutionary process of irreversible accumulation of deleterious mutations that lead to gene loss and the miniaturization of cellular components. Particularly, Microsporidia have remarkably small ribosomes in which the rRNA is reduced to the minimal enzymatic core. In this study, we analyzed microsporidian ribosomes to study an apparent impact of Muller's ratchet on structure of RNA and protein molecules in parasitic forms of life. Through mass spectrometry of microsporidian proteome and analysis of microsporidian genomes, we found that massive rRNA reduction in microsporidian ribosomes appears to annihilate the binding sites for ribosomal proteins eL8, eL27, and eS31, suggesting that these proteins are no longer bound to the ribosome in microsporidian species. We then provided an evidence that protein eS31 is retained in Microsporidia due to its non-ribosomal function in ubiquitin biogenesis. Our study illustrates that, while Microsporidia carry the same set of ribosomal proteins as non-parasitic eukaryotes, some ribosomal proteins are no longer participating in protein synthesis in Microsporidia and they are preserved from genome decay by having extra-ribosomal functions. More generally, our study shows that many components of parasitic cells, which are identified by automated annotation of pathogenic genomes, may lack part of their biological functions due to continuous genome decay.
Towards a Unified Theory of Mind and Brain.

A unified theory of how brains give rise to minds has been getting steadily developed for 60 years. This theory has explained data from thousands of interdisciplinary experiments, and scores of its predictions have been confirmed. The theory includes new computational paradigms called Complementary Computing and Laminar Computing that clarify the global organization of brain dynamics and behavior. It uses a small number of basic equations and modules to form modal architectures that model different modalities of intelligence. One of its models, Adaptive Resonance Theory, or ART, is currently the most advanced cognitive and neural theory of how advanced brains incrementally and stably learn to attend, recognize, and predict objects and events in a changing world. All the basic ART predictions have been confirmed by psychological and neural data. These results provide a firm foundation for further development of a Standard Theory of the Mind.
A theory of cooperation in games with an application to market socialism

AbstractEconomic theory has focused almost exclusively on how humans compete with each other in their economic activity, culminating in general equilibrium (Walras–Arrow–Debreu) and game theory (Co...
Classical Injective Solutions in the Large in Incompressible Nonlinear Elasticity

We consider a general class of parametrized displacement boundary value problems in incompressible nonlinear elasticity. We prove the existence of an unbounded solution branch of classical injective solutions emanating from the unforced stress-free reference configuration—a sharp global implicit function theorem. The ramifications of this are that there exists at least one solution for any given applied loading and/or there exists solutions of arbitrarily large there norm for some finite loading. We refer to this as solutions in the large. The nonlinear constraint equation enforcing incompressibility obviates the direct use of either the Leray–Schauder degree or an oriented degree previously developed for compressible problems. Instead we employ the nonlinear Fredholm degree for proper maps constructed in Fitzpatrick et al. (J Reine Angew Math 427:1–33, 1992); Pejsachowicz and Rabier (J Anal Math 76:265–288, 1998). We establish the requisite admissibility properties in the presence of the constraint equation before proving the main results.
A 20-year multicenter analysis of dialysis-dependent patients who had aortic or mitral valve replacement: Implications for valve selection.

Abstract Objective Valve selection in dialysis-dependent patients can be difficult because long-term survival is diminished and bleeding risks during anticoagulation treatment are greater in patients with renal failure. In this study we analyzed long-term outcomes of dialysis-dependent patients who underwent valve replacement to help guide optimal prosthetic valve type selection. Methods Dialysis-dependent patients who underwent aortic and/or mitral valve replacement at 3 institutions over 20 years were examined. The primary outcome was long-term survival. A Cox regression model was used to estimate survival according to 5 ages, presence of diabetes, and/or heart failure symptoms. Results Four hundred twenty-three available patients were analyzed; 341 patients had biological and 82 had mechanical valves. Overall complication and 30-day mortality rates were similar between the groups. Thirty-day readmission rates for biological and mechanical groups were 15% (50/341) and 28% (23/82; P = .005). Five-year survival was 23% and 33% for the biological and mechanical groups, respectively. After adjusting for age, New York Heart Association (NYHA) class, and diabetes using a multivariable Cox regression model, survival was similar between groups (hazard ratio, 0.93; 95% confidence interval, 0.66-1.29; P = .8). A Cox regression model on the basis of age, diabetes, and heart failure, estimated that patients only 30 or 40 years old, with NYHA class I-II failure without diabetes had a >50% estimated 5-year survival (P Conclusions Dialysis-dependent patients who underwent valve replacement surgery had poor long-term survival. Young patients without diabetes or NYHA III or IV symptoms might survive long enough to justify placement of a mechanical valve; however, a biological valve is suitable for most patients.
Synthesis, characterization, electrochemical properties and theoretical calculations of (BIAN) iron complexes

Abstract Reduction of the tetrahedral complex (BIAN)FeCl2 (6) (BIAN = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) in the presence of an arene, either as reaction solvent or in pentane solution affords a series of (BIAN)Fe(η6-arene) complexes (10–13). In the case of the sterically encumbered arene 2-methylnapthalene, 6 was converted to the (BIAN)Fe(COD) (14) (COD = 1,5-cyclooctadiene) complex first, before subsequent hydrogenation in the presence of 2-methylnaphthalene afforded the desired arene complex (15). The electronic structure of the arene complexes was interrogated, and the question of ligand redox non-innocence was addressed using X-ray diffraction studies as well as DFT and cyclic voltammetry.
Inequalities and Ehrhart delta-vectors

For any lattice polytope P, we consider an associated polynomial δ P (t) and describe its decomposition into a sum of two polynomials satisfying certain symmetry conditions. As a consequence, we improve upon known inequalities satisfied by the coefficients of the Ehrhart δ-vector of a lattice polytope. We also provide combinatorial proofs of two results of Stanley that were previously established using techniques from commutative algebra. Finally, we give a necessary numerical criterion for the existence of a regular unimodular lattice triangulation of the boundary of a lattice polytope.
Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1.

Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated...
Apparatus to Measure Optical Scatter of Coatings Versus Annealing Temperature

Light scattered by amorphous thin-film optical coatings limits the sensitivity of interferometric gravitational-wave detectors. We describe an imaging scatterometer to assess the role that crystal growth during annealing plays in this scatter.
Cultured circular smooth muscle from the rabbit colon

Although cultured vascular smooth muscle cells have been extensively characterized and investigated, there are very few studies of cultured intestinal smooth muscle cells. The aim of this study was to culture colonic smooth muscle (CSM) cells from the rabbit colon. Freshly isolated CSM cells from the circular muscle layer of the distal colon were prepared by collagenase digestion. In primary culture, CSM cells attached to the culture vessels by 48 to 72 h, proliferated by 3 to 7 d, and reached confluency by 14 to 17 d with a “hill-and-valley” pattern. Spontaneous contractions were not observed at any time at 21° or 37° C. Confluent primary cultures were greater than 95% CSM cells, as identified by intensely positive immunofluorescent staining to smooth muscle actin-specific CGA7 and muscle-specific HHF-35 monoclonal antibodies. Transmission electron microscopy of freshly isolated and proliferating CSM cells revealed ultrastructural features consistent with smooth muscle cells. We successfully cultured CSM cells of the rabbit from freshly isolated cells and validated these CSM cells by electron microscopy and immunocytochemical staining. These highly pure primary cultures may be used to investigate numerous aspects of CSM cell metabolism and physiology.
Carroll–Arabie Taxonomy

The Carroll–Arabie taxonomy of scaling methods gives a way to systematically describe data and models used in the computerized geometrical approach to scaling developed in psychometrics since 1960. Keywords: multidimensional scaling; cluster analysis; preference analysis
Factors predicting failure of retrieval of inferior vena cava filters.

Abstract Objective Inferior vena cava (IVC) filters have been commonly used to prevent pulmonary embolism in patients with deep vein thrombosis. However, IVC filters have been associated with risks, including IVC perforation, filter migration, fracture, and thrombosis. Filter retrieval has not always been successful. Our objective was to identify the factors associated with failure of retrieval of IVC filters. Methods The present study was an institutional review board-approved retrospective medical record review of patients who had undergone IVC filter retrieval attempts at the Department of Vascular Surgery at Cleveland Clinic from 2011 to 2018. The patients were identified by International Classification of Diseases code query, and data were gathered regarding demographics, filter position, procedure details, and patient outcomes. Computed tomography imaging and venography was used to determine the IVC filter location before retrieval. Results We identified 295 filter retrieval attempts in 294 patients. No procedural IVC ruptures, morbidity, or mortality occurred. Retrieval was successful for 249 filters (84.4%). The median filter dwell time was 196 days for the successful retrievals compared with 375 days for the failed retrieval attempts (P = .004). Penetration of the filter tines through the caval wall occurred in 291 filters (98.6%). However, the hook/apex (HA) of 31 filters (10.5%) had become embedded or had penetrated through the caval wall. The hook/apex and collar (HA+C) of 33 filters (11.2%) were embedded or had penetrated through the caval wall. The failure rate of filter retrieval with the HA embedded was 48.4% (15 of 31). The failure rate with the HA+C embedded was 66.7% (22 of 33). Finally, the failure rate for filters without these issues was 3.9% (9 of 231). The failure rate for HA and HA+C was greater than that for those without these issues (P Conclusions Retrieval should be attempted for all IVC filters, irrespective of the chronicity and complexity, given the procedural safety. Tine penetration was nearly ubiquitous; however, IVC filters with the HA or HA+C imbedded into or penetrating through the caval wall was a predictor of retrieval failure.
Phylogenetic Analysis with Improved Parameters Reveals Conservation in lncRNA Structures.

Abstract The existence of evolutionary conservation in base pairing is strong evidence for functional elements of RNA structure, although available tools for rigorous identification of structural conservation are limited. R-scape is a recently developed program for statistical prediction of pairwise covariation from sequence alignments, but it initially showed limited utility on long RNAs, especially those of eukaryotic origin. Here we show that R-scape can be adapted for a more powerful analysis of structure conservation in long RNA molecules, including mammalian lncRNAs.
Strategy adoption depends on characteristics of the instruction, learner, and strategy.

Why do people change their strategies for solving problems? In this research, we tested whether negative feedback and the context in which learners encounter a strategy influence their likelihood of adopting that strategy. In particular, we examined whether strategy adoption varied when learners were exposed to a target strategy in isolation, in conjunction with their own current strategy, and in conjunction with another novel strategy. We also investigated the roles of individual differences, including learners’ need for cognition and their confidence in their current strategies. In Study 1, undergraduate participants who encountered a target strategy in isolation were more likely to adopt it than participants who encountered it in the context of their own current strategy. Negative feedback, low confidence, and high need for cognition also predicted greater adoption. In Study 2, we examined whether rates of strategy adoption depended on the target strategy itself. Indeed, participants were more likely to adopt one strategy than the other, and the effects of feedback also varied across strategies. Individual differences—need for cognition and confidence—also influenced patterns of strategy adoption. These results suggest that strategy adoption depends on the confluence of many factors, including the context in which a target strategy is introduced, characteristics of the learner, and characteristics of the strategy itself.
Identifying structural variants using linked-read sequencing data

Motivation Structural variation, including large deletions, duplications, inversions, translocations and other rearrangements, is common in human and cancer genomes. A number of methods have been developed to identify structural variants from Illumina short-read sequencing data. However, reliable identification of structural variants remains challenging because many variants have breakpoints in repetitive regions of the genome and thus are difficult to identify with short reads. The recently developed linked-read sequencing technology from 10X Genomics combines a novel barcoding strategy with Illumina sequencing. This technology labels all reads that originate from a small number (∼5 to 10) DNA molecules ∼50 Kbp in length with the same molecular barcode. These barcoded reads contain long-range sequence information that is advantageous for identification of structural variants. Results We present Novel Adjacency Identification with Barcoded Reads (NAIBR), an algorithm to identify structural variants in linked-read sequencing data. NAIBR predicts novel adjacencies in an individual genome resulting from structural variants using a probabilistic model that combines multiple signals in barcoded reads. We show that NAIBR outperforms several existing methods for structural variant identification-including two recent methods that also analyze linked-reads-on simulated sequencing data and 10X whole-genome sequencing data from the NA12878 human genome and the HCC1954 breast cancer cell line. Several of the novel somatic structural variants identified in HCC1954 overlap known cancer genes. Availability and implementation Software is available at compbio.cs.brown.edu/software. Supplementary information Supplementary data are available at Bioinformatics online.
Carbon Nanotubes, Synthesis, Growth and Orientation Control

The combustion synthesis of carbon nanotubes is reviewed, examining their formation and control in diffusion flames. The production of CNTs in the absence of a catalyst, the range of morphology of nanostructures when a catalyst is employed, control of the growth and orientation of CNTs and their arrays through the use of electric fields and the functional coating of CNTs with polymers using supercritical CO2 are discussed. Application of these techniques to other materials is discussed.Copyright © 2006 by ASME
One-pot allyl-/crotylboration-Prins cyclization of aldehydes

Abstract Multi-substituted tetrahydropyrans (THPs) have been prepared via a one-pot, In(OTf) 3 -catalyzed, sequential allyl-/crotylboration-Prins cyclization. The homoallylic borate intermediate formed during the allyl- and crotylboration was converted in situ to an oxocarbenium ion and trapped with a nucleophile. The reaction has been extended to include a one-pot allylboration–cross Prins cyclization as well.
Organometallic Chemistry in the Flowing Afterglow: A Review

The flowing afterglow technique, among the various mass spectroscopic methods that have been used to study ions and ion−molecule reactions in the gas phase, has provided a number of interesting results in organometallic chemistry. The flowing afterglow technique is particularly suited for the investigation of thermally relaxed species, since ions and ion−molecule reactions are carried out in a pressure regime where multiple collisions with inert gases occur. Many of these studies are reviewed in this paper, with particular emphasis on anionic organometallic chemistry.
A simple method for the oxidation of α-amino acid esters to α-oximino esters

Abstract Magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) was found to be an effective reagent for the oxidation of various α-amino acid esters to the corresponding α-oximino acid esters. This transformation could be completed under mild conditions within 2.5 h using 1.1 equiv of MMPP in THF. Clean oximino esters were obtained after quenching and extracting the reaction from sodium thiosulfate solution. The O-phosphorylated derivative of 2-oximinoglutarate exhibited slow binding inhibitory potency for the metallopeptidase prostate-specific membrane antigen (PSMA) with an IC 50 value of 58 nM.
Expected Reward Value and Reward Uncertainty Have Temporally Dissociable Effects on Memory Formation.

Anticipating rewards has been shown to enhance memory formation. Although substantial evidence implicates dopamine in this behavioral effect, the precise mechanisms remain ambiguous. Because dopami...
Asymmetric dihydroxylation of allenes

We have used asymmetric dihydroxylation (AD) of allenes in order to synthesize chiral α-hydroxy ketones. This methodology has been applied to several aryl-substituted allenes. We have found that electron donating groups on the aromatic ring increase the efficiency of the reaction.
Chemoselective allylic addition of allyltrichlorosilane to α-oxocarboxylic acids: synthesis of tertiary α-hydroxy carboxylic acids

Abstract Allyltrichlorosilane can add to α-oxocarboxylic acids in the presence of DMF and HMPA. The α-carboxylic substituent exerts a remarkable neighboring group effect on the reaction. The reaction presumably proceeds in an intramolecular fashion through a ‘rigid’ bicyclic transition state assembly involving a hypervalent silicate species, which produces the chemoselectivity approaching 100%.
Biarylcarboxamide inhibitors of phosphodiesterase IV and tumor necrosis factor-α

Abstract Tumor necrosis factor-α (TNF-α) has been implicated as a key mediator in the progression of rheumatoid arthritis. Inhibitors of phosphodiesterase IV (PDE IV) have been shown to inhibit the production of TNF-α by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Our efforts in a series of biarylcarboxamides have led to the identification of 8j (CP-353,164) as a potent inhibitor of PDE IV and TNF-α production.
Optically active fluorinated β-lactam building blocks: A novel fluorinated retroamide isostere.

Abstract A new and versatile synthesis of optically active α-fluoro-malonamides derivatives from enantiomerically pure 3-fluoro-2-azetidinones is described. A fluorinated retroamide isostere based on these α-fluoro-malonamide was introduced into a small peptidomiroetic for use as an HIV-1 protease inhibitor.
Microwave-Assisted Aqueous Krapcho Decarboxylation

The Krapcho decarboxylation of alkyl malonate derivatives has been adapted to aqueous microwave conditions. Various salt additives were examined, and both the cation and the anion impacted the facility of the reaction. A strong correlation was found between the pKa of the anion and the reaction rate, suggesting a straightforward base-catalyzed hydrolysis. Lithium sulfate gave the best results, obviating the need for DMSO co-solvent.
Confidence Analysis of DEER Data and Its Structural Interpretation with Ensemble-Biased Metadynamics

Abstract Given its ability to measure multicomponent distance distributions between electron-spin probes, double electron-electron resonance (DEER) spectroscopy has become a leading technique to assess the structural dynamics of biomolecules. However, methodologies to evaluate the statistical error of these distributions are not standard, often hampering a rigorous interpretation of the experimental results. Distance distributions are often determined from the experimental DEER data through a mathematical method known as Tikhonov regularization, but this approach makes rigorous error estimates difficult. Here, we build upon an alternative, model-based approach in which the distance probability distribution is represented as a sum of Gaussian components, and use propagation of errors to calculate an associated confidence band. Our approach considers all sources of uncertainty, including the experimental noise, the uncertainty in the fitted background signal, and the limited time span of the data collection. The resulting confidence band reveals the most and least reliable features of the probability distribution, thereby informing the structural interpretation of DEER experiments. To facilitate this interpretation, we also generalize the molecular simulation method known as ensemble-biased metadynamics (EBMetaD). This method, originally designed to generate maximal-entropy structural ensembles consistent with one or more probability distributions, now also accounts for the uncertainty in those target distributions exactly as dictated by their confidence bands. After careful benchmarks, we demonstrate the proposed techniques using DEER results from spin-labeled T4 lysozyme.
Synthesis of 4‐Methyl Pyrrolo[2,3‐b]xanthone, a Novel Ring System

Abstract A short, high yielding synthesis of a novel substituted pyrrolo[2,3-b]xanthone has been developed. The synthesis begins with a copper catalyzed Ullmann coupling reaction followed by and intramolecular Friedel-Crafts acylation reaction to establish the xanthone core structure. After a regioselective nitration, a Leimgruber-Batcho synthesis establishes the final pyrrole ring.
Are Four Oxygens Enough to Stabilize the N8 Cube? Dissociation Pathways of Cage Isomers of N8O4

Various all-nitrogen molecules have been examined as candidates for high energy density materials (HEDM), because of the energy release that would accompany the dissociation of such a molecule down to N2 molecules. Numerous molecules Nx have been shown to dissociate too easily to be a viable HEDM, including small Nx all-nitrogen cages. One possible solution to the instability of small Nx cages is oxygen insertion into the N−N bonds. Conversion of N−N bonds into N−O−N bonding groups would relieve much of the ring strain in small Nx cages, thereby stabilizing the molecule and possibly making the NxOy molecule a good HEDM. Several cage isomers of N8O4 are examined by theoretical calculations to evaluate their suitability as potential HEDM. Calculations are carried out with Hartree−Fock theory and Moller−Plesset perturbation theory (MP3 and MP4), using the CC-PVDZ basis set of Dunning. The relative thermodynamic stability of the isomers is discussed, along with dissociation energies for the various N8O4 cages.
DEBLOCKING OF DITHIOACETALS AND OXATHIOACETALS USING PERIODIC ACID UNDER MILD NONAQUEOUS CONDITIONS

Abstract A novel method for the deblocking of the dithioacetals and oxathioacetals is described. Periodic acid under nonaqueous conditions has been used for the deprotection of the dithio- and oxathio-derivatives to the corresponding carbonyl compounds. This simple high-yield transformation is conveniently carried out in nonaqueous medium and works well with complex sensitive aldehydes and in the presence of other protective groups.
A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes

RNA secondary structures have been increasingly recognized to play an important regulatory role in post-transcriptional gene regulation. We recently showed that RNA G-quadruplexes, which serve as cis-elements to recruit splicing factors, play a critical role in regulating alternative splicing during the epithelial-mesenchymal transition. In this study, we performed a high-throughput screen using a dual-color splicing reporter to identify chemical compounds capable of regulating G-quadruplex-dependent alternative splicing. We identify emetine and its analog cephaeline as small molecules that disrupt RNA G-quadruplexes, resulting in inhibition of G-quadruplex-dependent alternative splicing. Transcriptome analysis reveals that emetine globally regulates alternative splicing, including splicing of variable exons that contain splice site-proximal G-quadruplexes. Our data suggest the use of emetine and cephaeline for investigating mechanisms of G-quadruplex-associated alternative splicing.
Tandem reduction / intramolecular hydroxyalkylation of (3-hydroxyphenyl)alkanoates: a new regioselective approach to 1,8-dihydroxytetralins

Abstract 4-(3-hydroxyphenyl)-butanoates 4, on treatment with DIBALH, followed by hydrolytic work-up, undergo a novel completely regioselective intramolecular hydroxyalkylation reaction to give 1,8-dihydroxytetralins. The yield of the reaction depends heavily on the structure of starting material, best results being achieved with 3,3-disubstituted butanoates.
Catalytic, Formal Homo-Nazarov-Type Cyclizations of Alkylidene Cyclopropane-1,1-Ketoesters: Access to Functionalized Arenes and Heteroaromatics

A catalytic, formal homo-Nazarov-type cyclization of alkylidene cyclopropanes (ACPs) to give functionalized arenes and heteroaromatics is reported. In the presence of a Lewis acid catalyst, the ACP 1,1-ketoesters undergo distal bond cleavage to afford an allyl cation intermediate. Adjacent π-attack on the allyl cation then provides a six-membered ring that undergoes rapid aromatization. In these cases, benzenoid products are formed in up to 98% yield. Strategic choice of the substitution about the ACP allows for the generation of other useful isomeric products in good yields.
Classifying cancer genome aberrations by their mutually exclusive effects on transcription.

Malignant tumors are typically caused by a conglomeration of genomic aberrations—including point mutations, small insertions, small deletions, and large copy-number variations. In some cases, specific chemotherapies and targeted drug treatments are effective against tumors that harbor certain genomic aberrations. However, predictive aberrations (biomarkers) have not been identified for many tumor types and treatments. One way to address this problem is to examine the downstream, transcriptional effects of genomic aberrations and to identify characteristic patterns. Even though two tumors harbor different genomic aberrations, the transcriptional effects of those aberrations may be similar. These patterns could be used to inform treatment choices. We used data from 9300 tumors across 25 cancer types from The Cancer Genome Atlas. We used supervised machine learning to evaluate our ability to distinguish between tumors that had mutually exclusive genomic aberrations in specific genes. An ability to accurately distinguish between tumors with aberrations in these genes suggested that the genes have a relatively different downstream effect on transcription, and vice versa. We compared these findings against prior knowledge about signaling networks and drug responses. Our analysis recapitulates known relationships in cancer pathways and identifies gene pairs known to predict responses to the same treatments. For example, in lung adenocarcinomas, gene-expression profiles from tumors with somatic aberrations in EGFR or MET were negatively correlated with each other, in line with prior knowledge that MET amplification causes resistance to EGFR inhibition. In breast carcinomas, we observed high similarity between PTEN and PIK3CA, which play complementary roles in regulating cellular proliferation. In a pan-cancer analysis, we found that genomic aberrations in BRAF and VHL exhibit downstream effects that are clearly distinct from other genes. We show that transcriptional data offer promise as a way to group genomic aberrations according to their downstream effects, and these groupings recapitulate known relationships. Our approach shows potential to help pharmacologists and clinical trialists narrow the search space for candidate gene/drug associations, including for rare mutations, and for identifying potential drug-repurposing opportunities.
Total synthesis of (+/-)-dysibetaine

The marine natural product dysibetaine was synthesized in racemic form from a levulinic acid derivative using a convertible isocyanide and an ammonium acetate in the Ugi 4-center-3-component condensation reaction.
RNA structure inference through chemical mapping after accidental or intentional mutations

Despite the critical roles RNA structures play in regulating gene expression, sequencing-based methods for experimentally determining RNA base pairs have remained inaccurate. Here, we describe a multidimensional chemical-mapping method called “mutate-and-map read out through next-generation sequencing” (M2-seq) that takes advantage of sparsely mutated nucleotides to induce structural perturbations at partner nucleotides and then detects these events through dimethyl sulfate (DMS) probing and mutational profiling. In special cases, fortuitous errors introduced during DNA template preparation and RNA transcription are sufficient to give M2-seq helix signatures; these signals were previously overlooked or mistaken for correlated double-DMS events. When mutations are enhanced through error-prone PCR, in vitro M2-seq experimentally resolves 33 of 68 helices in diverse structured RNAs including ribozyme domains, riboswitch aptamers, and viral RNA domains with a single false positive. These inferences do not require energy minimization algorithms and can be made by either direct visual inspection or by a neural-network–inspired algorithm called M2-net. Measurements on the P4–P6 domain of the Tetrahymena group I ribozyme embedded in Xenopus egg extract demonstrate the ability of M2-seq to detect RNA helices in a complex biological environment.
Synthesis of cyclic allyl vinyl ethers using Pt(II)-catalyzed isomerization of oxo-alkynes

Abstract Several alkynyl epoxides and one alkynyl allyl alcohol were isomerized to cyclic allyl vinyl ethers (3,4-dihydro-2H-1,4-oxazines) using PtCl2 as the catalyst. Three of these allyl vinyl ethers were converted to 2-hydroxymorpholine derivatives by hydrolysis and two were converted to piperidine derivatives by thermal Claisen rearrangement.
Organotransition-Metal Chemistry and Homogeneous Catalysis in Aqueous Solution

Publisher Summary This chapter reviews both the organo-metallic compounds that can be obtained in aqueous solution and the catalytic systems that can be used in this solvent. In general for transition-metal systems, water-soluble organometallics are known for the kinetically inert metal ions. Alkylcobalt (III) complexes can also be synthesized in aqueous solution. Two of the best-known systems are methylcobalamin and a group of related cobaloximes, and alkylcobalt (III) complexes having ancillary cyanide ligands. As with the chromium (III) system, alkyl cobalt (III) complexes having dimethylglyoxime (DMG) or cyanide ligands can be synthesized by reaction of the cobalt (II) precursor with alkyl halides. Pulse radiolysis has been used to study the transient formation and decomposition of cobalt–alkyl bonds in aqueous solution in the same manner as it has been used for chromium alkyls. In general for all of these metal–alkyl bond homolysis reactions of the aquo complexes, steric hindrance facilitates the reaction. Since many organometallic compounds are stabilized by tertiary phosphines and phosphites, then if organometallic chemistry is to find major applications in aqueous solution it is necessary that these complexes be made compatible with such a solvent system.
Broadly Effective Enantioselective Diels−Alder Reactions of 1-Amino-substituted-1,3-butadienes

A broad range of substituted 1-amino-1,3-butadienes undergo enantioselective Diels−Alder reactions with methacrolein in the presence of 5 mol % of Cr(III)-salen complex 1. The reactions are carried out conveniently, at room temperature, and they afford the cycloadducts in high yields and excellent ee's.