cssi/SciSciGPT-SciSciNet huggingface dataset:
Internet of Things: How to Avoid Short-Term Errors and Ensure Lasting Adoption

The Internet of Things is at risk of becoming a victim of its own popularity. Today, the IoT market is generating $200 billion in revenue, a number expected to triple in the next 10 years. But a rush to market by developers of consumer IoT products and services has been accompanied by shortcuts in design, particularly in information security, usability and branding. Several embarrassing and highly public data breaches have left buyers increasingly wary of embracing smart technology, slowing market adoption for products both good and otherwise. These early market failures must be corrected, and quickly, if the IoT is to reach its full potential. This article offers five pragmatic solutions to the IoT's current problems.
Passive Timing Stabilization over a 33-km Single Mode Fiber Link using Temporal Imaging

We demonstrate a temporal imaging system that uses parametric wavelength conversion and dispersion to distribute a stabilized clock and passively correct all-optically for environmental distortions. We demonstrate clock distribution with less than one picosecond drift over one thousand seconds through a 33-km single-mode fiber link.
Energy Stable Semi-implicit Schemes for Allen–Cahn–Ohta–Kawasaki Model in Binary System

In this paper, we propose a first order energy stable linear semi-implicit method for solving the Allen–Cahn–Ohta–Kawasaki equation. By introducing a new nonlinear term in the Ohta–Kawasaki free energy functional, all the system forces in the dynamics are localized near the interfaces which results in the desired hyperbolic tangent profile. In our numerical method, the time discretization is done by some stabilization technique in which some extra nonlocal but linear term is introduced and treated explicitly together with other linear terms, while other nonlinear and nonlocal terms are treated implicitly. The spatial discretization is performed by the Fourier collocation method with FFT-based fast implementations. The energy stabilities are proved for this method in both semi-discretization and full discretization levels. Numerical experiments indicate the force localization and desire hyperbolic tangent profile due to the new nonlinear term. We test the first order temporal convergence rate of the proposed scheme. We also present hexagonal bubble assembly as one type of equilibrium for the Ohta–Kawasaki model. Additionally, the two-third law between the number of bubbles and the strength of long-range interaction is verified which agrees with the theoretical studies.
Top-K Off-Policy Correction for a REINFORCE Recommender System

Industrial recommender systems deal with extremely large action spaces -- many millions of items to recommend. Moreover, they need to serve billions of users, who are unique at any point in time, making a complex user state space. Luckily, huge quantities of logged implicit feedback (e.g., user clicks, dwell time) are available for learning. Learning from the logged feedback is however subject to biases caused by only observing feedback on recommendations selected by the previous versions of the recommender. In this work, we present a general recipe of addressing such biases in a production top-K recommender system at Youtube, built with a policy-gradient-based algorithm, i.e. REINFORCE. The contributions of the paper are: (1) scaling REINFORCE to a production recommender system with an action space on the orders of millions; (2) applying off-policy correction to address data biases in learning from logged feedback collected from multiple behavior policies; (3) proposing a novel top-K off-policy correction to account for our policy recommending multiple items at a time; (4) showcasing the value of exploration. We demonstrate the efficacy of our approaches through a series of simulations and multiple live experiments on Youtube.
High Performance Parallel Computing with Clouds and Cloud Technologies

Infrastructure services (Infrastructure-as-a-service), provided by cloud vendors, allow any user to provision a large number of compute instances fairly easily. Whether leased from public clouds or allocated from private clouds, utilizing these virtual resources to perform data/compute intensive analyses requires employing different parallel runtimes to implement such applications. Among many parallelizable problems, most “pleasingly parallel” applications can be performed using MapReduce technologies such as Hadoop, CGL-MapReduce, and Dryad, in a fairly easy manner. However, many scientific applications, which have complex communication patterns, still require low latency communication mechanisms and rich set of communication constructs offered by runtimes such as MPI. In this paper, we first discuss large scale data analysis using different MapReduce implementations and then, we present a performance analysis of high performance parallel applications on virtualized resources.
Happy partisans and extreme political views: The impact of national versus local representation on well-being

Abstract The political party of elected officials can affect the happiness of the voting public through several different channels. Partisan voters will be happier whenever a member of their party controls political office regardless of the policies implemented. It is hypothesized that congruence between individual party identity and state politician affiliations should have a greater impact on citizen happiness than congruence with politicians at the national level due to results from the literature on Tiebout sorting. It is further hypothesized that individuals with extreme ideological views may report greater happiness as their ideology fulfills basic psychological needs for certainty and structure. Using data from the Generalized Social Survey the effect of party congruence of individuals with national and state politicians on happiness is estimated. The effect of extreme ideological political views on happiness is also estimated. Results find that congruence with presidential party affiliation has a much greater impact on happiness than congruence with national legislative affiliation, gubernatorial, or state legislative affiliation contradicting the hypothesis. Those who possess extreme political views are also found to report higher levels of happiness.
NOODL: Provable Online Dictionary Learning and Sparse Coding

We consider the dictionary learning problem, where the aim is to model the given data as a linear combination of a few columns of a matrix known as a dictionary, where the sparse weights forming the linear combination are known as coefficients. Since the dictionary and coefficients, parameterizing the linear model are unknown, the corresponding optimization is inherently non-convex. This was a major challenge until recently, when provable algorithms for dictionary learning were proposed. Yet, these provide guarantees only on the recovery of the dictionary, without explicit recovery guarantees on the coefficients. Moreover, any estimation error in the dictionary adversely impacts the ability to successfully localize and estimate the coefficients. This potentially limits the utility of existing provable dictionary learning methods in applications where coefficient recovery is of interest. To this end, we develop NOODL: a simple Neurally plausible alternating Optimization-based Online Dictionary Learning algorithm, which recovers both the dictionary and coefficients exactly at a geometric rate, when initialized appropriately. Our algorithm, NOODL, is also scalable and amenable for large scale distributed implementations in neural architectures, by which we mean that it only involves simple linear and non-linear operations. Finally, we corroborate these theoretical results via experimental evaluation of the proposed algorithm with the current state-of-the-art techniques. Keywords: dictionary learning, provable dictionary learning, online dictionary learning, non-convex, sparse coding, support recovery, iterative hard thresholding, matrix factorization, neural architectures, neural networks, noodl, sparse representations, sparse signal processing.
Evaluating the impact of a newly added commuter rail system on bus ridership: a grouped ordered logit model approach

The study develops a comprehensive and statistically valid framework to study the impact of new public transportation infrastructure (SunRail commuter train) on existing public transit infrastructure (Lynx bus) in the Orlando metropolitan region. The data for the study is drawn from bus ridership information for six 4-month time periods - 3 prior and 3 after SunRail began operations - allowing us to study time varying effects of SunRail on bus ridership. The current research formulates and estimates an innovative grouped ordered response structure for the ridership analysis. To measure the impact of commuter rail on stop level bus ridership (defined as boarding and alighting), the model system controls for a host of independent variables including stop level attributes, transportation infrastructure, transit infrastructure, land use, built environment, demographic and socioeconomic variables. The proposed model also accommodates for common unobserved factors affecting ridership as well as repeated ridership measures for each stop.
The Big Ten IPE Academic Alliance: A regional approach to developing Interprofessional Education and practice

Abstract Interprofessional practice and education (IPE) efforts has greatly increased in the past few years, primarily through the leadership of several national and international organizations. These organizations have sponsored forums for information exchange and best practices, which has significantly influenced the development of programs across various educational institutions and practice environments. Several regional groups have emerged, organized around a common purpose and geographic proximity, to share ideas and implement new IPE programs across the cooperating organizations. This article describes the history and growth of one of the newer regional groups, the Big Ten IPE Academic Alliance. Included in this discussion is how the group was created, its governing structure and the various results of its efforts. The intent is to provide expanded guidance how to develop regional groups that are effective vehicles for the successful implementation of IPE within educational and health settings.
An Autonomous GNSS Wave Sensor Module for Deployment on Existing Buoy Infrastructure : Comparison and Validation of Co-Located GNSS and Accelerometer Directional Wave Sensors

For this paper a standalone OEM (Original Equipment Manufactuer) GNSS wave sensor module is co-located on an existing accelerometer-based three-meter diameter disc wave buoy for statistical comparison. Additionally, a GNSS wave sensor is placed on an existing, already deployed, nearby navigational buoy 700 meters away to assess suitability as a platform for a GNSS directional wave height sensor. Both sensors were deployed in 30 meters depth of water in Herring Cove, Nova Scotia, Canada.
A Comparison of Multilevel Imputation Schemes for Random Coefficient Models: Fully Conditional Specification and Joint Model Imputation with Random Covariance Matrices.

AbstractLiterature addressing missing data handling for random coefficient models is particularly scant, and the few studies to date have focused on the fully conditional specification framework an...
The International Conference on Intelligent Biology and Medicine (ICIBM) 2018: genomics with bigger data and wider applications.

The sixth International Conference on Intelligent Biology and Medicine (ICIBM) took place in Los Angeles, California, USA on June 10–12, 2018. This conference featured eleven regular scientific sessions, four tutorials, one poster session, four keynote talks, and four eminent scholar talks. The scientific program covered a wide range of topics from bench to bedside, including 3D Genome Organization, reconstruction of large scale evolution of genomes and gene functions, artificial intelligence in biological and biomedical fields, and precision medicine. Both method development and application in genomic research continued to be a main component in the conference, including studies on genetic variants, regulation of transcription, genetic-epigenetic interaction at both single cell and tissue level and artificial intelligence. Here, we write a summary of the conference and also briefly introduce the four high quality papers selected to be published in BMC Genomics that cover novel methodology development or innovative data analysis.
Slope–Ratio Assay†

Slope-ratio assays are similar to parallel-line assays insofar as both are indirect analytical assays, which aim to estimate the potency of a test preparation relative to that of a standard. Slope-ratio assays are most often encountered in microbiologic applications. As with a parallel-line assay, the key assumption is that the expected response to a given dose of the test preparation is the same as that which would be obtained from the standard preparation administered at a dose that is ρ times the given dose. As in parallel-line assays, the parameter ρ is known as the relative potency. Unlike the parallel-line assay, the expected response, which is almost always continuous, is linear in the dose, not its logarithm. The graphs of the response against dose for test and standard preparation will be straight lines of different slopes and common intercept, as the assumptions of the assay demand the same outcome for standard and test preparations when the dose is zero. The analysis can be accomplished by a multiple regression, with the estimator of ρ being the ratio of the slope estimators. Interval estimates are often obtained using Fieller's theorem. Keywords: dose metameter; Fieller's theorem; linear model; microbiology; relative potency; slope-ratio assay
15 – Endocrine System

Endocrine organs are richly vascularized ductless organs that produce hormones. The epithelial cells of the organ secrete their hormone product directly into the bloodstream where, upon binding with specific receptors in target organs, cellular functions are affected. The endocrine system includes not only the endocrine glands (pineal, pituitary, thyroid, parathyroid, and adrenal) but also single cells and small clusters of cells in the thorax and abdomen known as paraganglia. This chapter addresses the thyroid, parathyroid, adrenal, pituitary and pineal glands, and paraganglia. In addition to size differences, several features of endocrine tissues differ between rodents and humans, and often between rodents.
Tensions and Contradictions in Interns' Communication about Unexpected Pregnancy Loss.

Early miscarriage is an unexpected pregnancy complication that affects up to 25% of pregnant women. Physicians are often tasked with delivering the bad news of a pregnancy loss to asymptomatic wome...
Phage-Assisted Evolution of Bacillus methanolicus Methanol Dehydrogenase 2.

Synthetic methylotrophy, the modification of organisms such as E. coli to grow on methanol, is a longstanding goal of metabolic engineering and synthetic biology. The poor kinetic properties of NAD-dependent methanol dehydrogenase, the first enzyme in most methanol assimilation pathways, limit pathway flux and present a formidable challenge to synthetic methylotrophy. To address this bottleneck, we used a formaldehyde biosensor to develop a phage-assisted noncontinuous evolution (PANCE) selection for variants of Bacillus methanolicus methanol dehydrogenase 2 (Bm Mdh2). Using this selection, we evolved Mdh2 variants with up to 3.5-fold improved Vmax. The mutations responsible for enhanced activity map to the predicted active site region homologous to that of type III iron-dependent alcohol dehydrogenases, suggesting a new critical region for future methanol dehydrogenase engineering strategies. Evolved Mdh2 variants enable twice as much 13C-methanol assimilation into central metabolites than previously rep...
Polymers for extended-release administration

Developing strategies to deliver the required dose of therapeutics into target tissues and cell populations within the body is a principal aim of controlled release and drug delivery. Specifically, there is an interest in developing formulations that can achieve drug concentrations within the therapeutic window, for extended periods of time, with tunable release profiles, and with minimal complication and distress for the patient. To date, drug delivery systems have been developed to serve as depots, triggers, and carriers for therapeutics including small molecules, biologics, and cell-based therapies. Notably, the efficacy of these systems is intricately tied to the manner in which they are administered. For example, systemic and oral routes of administration are common, but both can result in rapid clearance from the organism. Towards this end, what formulation and administration route strategies are available to prolong the bioavailability of therapeutics? Here, we discuss historical and modern drug delivery systems, with the intention of exploring how properties including formulation, administration route and chemical structure influence the ability to achieve extended-release drug release profiles within the body.
Effects of adjuvant radiation therapy on survival for patients with resected primary tracheal carcinoma: an analysis of the National Cancer Database.

Objective(s) To identify predictors for receiving adjuvant radiation therapy (RT) and investigate the impact of adjuvant RT on survival for patients with resected primary tracheal carcinoma (PTC). Methods The National Cancer database was queried for patients with PTC diagnosed from 2004 to 2014 undergoing resection. Patients who died within 30 days of resection were excluded to minimize immortal time bias. Kaplan-Meier methods, Cox regression modeling and propensity score weighted (PSW) log-rank tests were considered to assess the relationship between adjuvant RT and overall survival (OS). Logistic regression was performed to identify predictors associated with receiving adjuvant RT. Results A total of 549 patients were identified with 300 patients (55%) receiving adjuvant RT. Squamous cell carcinoma (SCC) was the most common histology with 234 patients (43%). Adenoid cystic carcinoma (ACC) was second most frequent with 180 patients (33%). Adjuvant RT was not associated with OS by multivariable Cox analysis or PSW log-rank test (P values > 0.05). Patients with positive surgical margins (odds ratio (OR) 1.80, confidence interval (CI) 1.06-3.07) were more likely to receive adjuvant RT than those with negative surgical margins. Patients with ACC (OR 6.53, CI 3.57-11.95) were more likely to receive adjuvant RT compared with SCC. Conclusions Adjuvant RT was not significantly associated with OS for patients with resected PTC in this analysis. Surgical margin status and tumor histology were associated with receiving adjuvant RT. Further investigations including prospective registry studies capturing radiation technique and treatment volumes are needed to better define which patients with resected PTC may benefit from adjuvant RT.
Continuous manufacturing – the Green Chemistry promise?

Continuous manufacturing and Green Chemistry, are two promising approaches to synthesis with underutilized potential that are gaining traction by the wider pharmaceutical community. We review Green Chemistry advances resulting when transitioning to continuous manufacturing with focus on Green Chemistry elements inherent in flow chemistry and related separation processes. Case studies of continuous manufacturing represented by the F3 (Flexible, Fast, and Future) project, cGPM manufacturing at Eli Lilly, and the MIT pharmaceuticals on demand projects provide examples of Green Chemistry advances realised. Throughout the review, Green Chemistry advances are identified in terms of the pertinent principles of Green Chemistry. A count of the occurrences of the different principles of Green Chemistry reveals that the principle of prevention greatly overshadows all other principles.
1,4-Disubstituted and 1,4,5-Trisubstituted 2-[(Benzotriazol-1-yl)methyl]pyrroles as Versatile Synthetic Intermediates.

The CH2Bt substituent, unlike previously used CH2X substituents, enables (i) the synthetic elaboration of pyrroles with unsubstituted ring positions and (ii) electrophilic as well as nucleophilic s...
PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism.

Summary Insulin stimulates the conversion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), which mediates downstream cellular responses. PI(4,5)P2 is produced by phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) and by phosphatidylinositol-5-phosphate 4-kinases (PIP4Ks). Here, we show that the loss of PIP4Ks (PIP4K2A, PIP4K2B, and PIP4K2C) in vitro results in a paradoxical increase in PI(4,5)P2 and a concomitant increase in insulin-stimulated production of PI(3,4,5)P3. The reintroduction of either wild-type or kinase-dead mutants of the PIP4Ks restored cellular PI(4,5)P2 levels and insulin stimulation of the PI3K pathway, suggesting a catalytic-independent role of PIP4Ks in regulating PI(4,5)P2 levels. These effects are explained by an increase in PIP5K activity upon the deletion of PIP4Ks, which normally suppresses PIP5K activity through a direct binding interaction mediated by the N-terminal motif VMLΦPDD of PIP4K. Our work uncovers an allosteric function of PIP4Ks in suppressing PIP5K-mediated PI(4,5)P2 synthesis and insulin-dependent conversion to PI(3,4,5)P3 and suggests that the pharmacological depletion of PIP4K enzymes could represent a strategy for enhancing insulin signaling.
β-Amino alcohols from amino acids: Chelation control via schiff bases.

Abstract Sequential addition of iBu2AIH and RLi or RMgX to Schiff base esters derived from amino acids provides a simple route to β-amino alcohols. The reaction procedes without racemization, and with high threo selectivity. Several representative sphingosines are synthesized.
Trisubstituted aziridine ring-opening by phenol derivatives: stereo- and regioselective formation of chiral tertiary alkyl-aryl ethers.

An unprecedented stereo- and regioselective trisubstituted aziridine ring-opening by phenol derivatives was discovered. The reaction features very mild reaction conditions and broad functional group compatibility, which provides a good method for the stereoselective formation of tertiary alkyl-aryl ethers in highly functionalized systems.
In Search of Cyclohexane-like Sn612-: Synthesis of Li2Ln5Sn7 (Ln = Ce, Pr, Sm, Eu) with an Open-Chain Heptane-like Sn716- Instead

The title compounds were prepared by direct reactions of the corresponding elements at high temperature. They are isostructural and crystallize in the chiral orthorhombic space group P212121 (Li2Ce5Sn7: a = 6.273(1), b = 13.839(2), and c = 17.467(2) A; Li2Pr5Sn7: a = 6.241(1), b = 13.762(2), and c = 17.367(1) A; Li2Sm5Sn7: a = 6.262 (1), b = 13.809(1), and c = 17.432(1) A; Li2Eu5Sn7: a = 6.165(1), b = 13.562(2), and c = 17.128(1) A). The structure contains isolated Sn7 oligomers that resemble the carbon core of an open-chain heptane molecule C7H16. Although these heptamers are stacked along the a axis at a distance that is comparable to the distances within the heptamer, electronic structure calculations show that this intermolecular contact is nonbonding for a formal charge of 16− or higher per heptamer. A hypothetical lower charge of 14−, on the other hand, leads to positive and substantial bond-overlap population that would result in branched infinite chains of ∞[Sn714-]. Magnetic measurements of t...
COMPASS: An Open-Source, General-Purpose Software Toolkit for Computational Psychiatry.

Mathematical modeling of behavior during psychophysical tasks, referred to as "computational psychiatry", could greatly improve our understanding of mental disorders. One barrier to broader adoption of computational methods is that they often require advanced statistical modeling and mathematical skills. Biological and behavioral signals often show skewed or non-Gaussian distributions, and few of toolboxes and analytical platforms are capable of processing these categories of signals. We developed the Computational Psychiatry Adaptive State-Space (COMPASS) toolbox, an open-source MATLAB-based software package, to be easy to use and capable of integrating signals with a variety of distributions. COMPASS has tools to process signals with continuous-valued and binary measurements or signals with incomplete - missing or censored - measurements, which makes it well suited for processing signals captured during psychophysical tasks After specifying a few parameters in a small set of user-friendly functions, COMPASS allows the user to efficiently fit a wide range of computational behavioral models. The model output can be analyzed as an experimental outcome or used as a regressor for neural data and can be tested using goodness-of-fit methods. Here, we demonstrate that COMPASS can replicate two computational behavior analyses from different groups. COMPASS replicates and, in one case, slightly improves on the original modeling results. We also demonstrate COMPASS application in a censored-data problem and compare its performance result with naive estimation methods. This flexible, general-purpose toolkit should accelerate the use of computational modeling in psychiatric neuroscience.
Enantioselective synthesis of "quaternary" 1,4-benzodiazepin-2-one scaffolds via memory of chirality.

Glycine-derived 1,4-benzodiazepine-2-ones such as diazepam are chiral by virtue of the boat-shaped conformation of the diazepine ring and exist as a racemic mixture of conformational enantiomers. H...
Desymmetrization of Prochiral Diesters Via Transition Metal Catalyzed Reactions

The development of asymmetric induction in palladium catalyzed allylic alkylation has led to the notion of creating a chiral pocket. Two platforms for ligand design that may generate such “chiral space” evolve from derivatizing chiral diols or diamines with 2-diphenylphosphinobenzoic acid or chiral diacids with 2-diphenylphosphinoaniline. Palladium complexes derived from such ligands effect excellent enantiodiscrimination in the desymmetrization of esters of meso-cycloalk-2-en-1,4-diols and gem dicarboxylates of α,β-unsaturated aldehydes. These methods prove useful for asymmetric syntheses of carbanucleosides, nucleosides, and the antitumor alkaloid (+)-pancratistatin.
Compounds based on meso-tri(4-pyridyl)-p-acrylamidophenylporphyrin able to interact with DNA

A new type of porphyrinyl-nucleoside was synthesized by the Heck reaction of meso-tri(4-pyndyl)-p-acrylamidophenylporphyrin with (+)5-iodo-2′-deoxyuridine. The porphyrin used in this reaction was also applied in obtaining a water soluble porphyrin polymer and a copolymer with acrylamide. The porphyrinyl-nucleoside and the polymer and copolymer were investigated for their interaction with ds DNA, oligonucleotides and oligonucleotide duplexes. The extend of the red-shift of the Soret band of porphyrins and the slowing of the mobolity of DNA during electrophoresis of the interacting systems suggested that intercalation of cationic porphyrin units into ds DNA cannot be solely responsible for the observed phenomena.
An unprecedented, tandem Aldol-Grob reaction sequence

The authors report an unprecedented, tandem Aldol-Grob sequence involving the reaction of ketones with aromatic aldehydes in nonnucleophilic solvents in the presence of boron trifluoride. Although a detailed study of the reaction mechanism has not yet been completed, the consistent formation of (E)-alkene products, as well as the fact that aromatic aldehydes appear to be required, would point toward the intermediacy of a carbocation derivative. A reasonable mechanism would involve the formation of the mixed aldol followed by the formation and subsequent nonsynchronous ring opening of a lactol. The proposed fragmentation is reminiscent of two-step Grob fragmentations that have been reported for N-halo-{alpha}-amino acids and cyclobutane hemiacetals as well as the acid-catalyzed fragmentation of {beta}-hydroxy acetals. The authors examined the effect of various acids on the reaction sequence in order to ascertain which would be most efficient. They conclude that boron trifluoride is the most effective of the acids studied in achieving the new tandem condensation-cleavage sequence.
Regiocontrolled [3+2] quinone-nitrile oxide entry to type II polyketide building blocks

Bromine substituents on naphthoquinones effectively activate and orient the [3+2] dipolar cycloaddition reaction with nitrile oxides to generate regiodefined type II polyketide building blocks.
Synthesis of medium-sized rings using the intramolecular Pauson–Khand reaction

Abstract The dicobalthexacarbonyl alkyne complex of a series of enynes templated on aromatic rings has been shown to undergo the Pauson–Khand reaction to generate medium-sized rings.
Target Conditioned Sampling: Optimizing Data Selection for Multilingual Neural Machine Translation.

To improve low-resource Neural Machine Translation (NMT) with multilingual corpus, training on the most related high-resource language only is generally more effective than us- ing all data available (Neubig and Hu, 2018). However, it remains a question whether a smart data selection strategy can further improve low-resource NMT with data from other auxiliary languages. In this paper, we seek to construct a sampling distribution over all multilingual data, so that it minimizes the training loss of the low-resource language. Based on this formulation, we propose and efficient algorithm, (TCS), which first samples a target sentence, and then conditionally samples its source sentence. Experiments show TCS brings significant gains of up to 2 BLEU improvements on three of four languages we test, with minimal training overhead.
Acylnitrilium ions. Versatile new intermediates for the Synthesis of highly functionalized heterocycles.

Abstract Acylnitrilium ions, generated by the exposure of α-ketoimidoyl chlorides to AgBF4, readily engage suitably disposed sites of molecular unsaturation in cyclization reactions leading to heterocyclic ring systems. This novel method for annulation is applicable to the construction of 5, 6, and 7 membered rings and is particularly useful for the @Synthesis of polyfunctional heterocycles possessing quaternary sites in the β-position to nitrogen.
‘Buckybowls’—introducing curvature by solution phase synthesis

Abstract New, non-pyrolytic methods are presented for the synthesis of curved-surface, polynuclear aromatic hydrocarbons related to the fullerenes. Tetrabromocorannulene is conveniently prepared on a large scale and then converted to corannulene, and also used as a synthon for further elaboration.
Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles

Abstract Lithiated oxazolo[3,4- a ]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4- a ]benzimidazoles 5a – d in good yields as single diastereoisomers. ( R )-Benzimidazol-2-yl carbinols 6a – d were obtained upon hydrolysis under acidic conditions of 1 H ,3 H -oxazolo[3,4- a ]benzimidazole derivatives.
Dynamics and structure of room temperature ionic liquids

Abstract Room temperature ionic liquids (RTIL) are intrinsically interesting because they simultaneously have properties that are similar to organic liquids and liquid salts. In addition, RTILs are increasingly being considered for and used in technological applications. RTILs are usually composed of an organic cation and an inorganic anion. The organic cation, such as imidazolium, has alkyl chains of various lengths. The disorder in the liquid produced by the presence of the alkyl groups lowers the temperature for crystallization below room temperature and can also result in supercooling and glass formation rather than crystallization. The presence of the alkyl moieties also results in a segregation of the liquid into ionic and organic regions. In this article, experiments are presented that address the relationship between RTIL dynamics and structure. Time resolved fluorescence anisotropy measurements were employed to study the local environments in the organic and ionic regions of RTILs using a nonpolar chromophore that locates in the organic regions and an ionic chromophore that locates in the ionic regions. In the alkyl regions, the in plane and out of plane orientational friction coefficients change in different manners as the alkyl chains get longer. Both friction coefficients converge toward those of a long chain length hydrocarbon as the RTIL chains increase in length, which demonstrates that for sufficiently long alkyl chains the RTIL organic regions have properties similar to a hydrocarbon. However, putting Li + in the ionic regions changes the friction coefficients in the alkyl regions, which demonstrates that changes of the ion structural organization influences the organization of the alkyl chains. Optical heterodyne detected optical Kerr effect (OHD-OKE) experiments were used to examine the orientational relaxation dynamics of RTILs over times scales of a hundred femtoseconds to a hundred nanoseconds. Detailed temperature dependent studies in the liquid and supercooled state and analysis using schematic mode coupling theory (MCT) show that RTILs have bulk liquid orientational relaxation dynamics that are indistinguishable in their nature from common nonpolar organic liquids that supercool. This behavior of the RTILs occurs in spite of the segregation into ionic and organic regions. However, when small amounts of water are added to RTILs at room temperature, novel dynamics are observed for the RTILs with long alkyl chains that have not been observed in OHD-OKE experiments on organic liquids. The results are interpreted as water induced structure in the ionic regions that causes the long alkyl chains to organize and ‘lock up.’ The dynamical measurements indicate that this lock up is involved in the formation of RTIL gels that occur over a narrow range of water concentrations.
Novel 4,4-bis(trifluoromethyl) imidazolines as stereospecific and orally active acyl coa: Cholesterol acyltransferase (ACAT) inhibitors and antihypercholesterolemic agents

A new class of very potent, systemically-active ACAT inhibitors based on a 4,4-bis(trifluoromethyl)imidazoline ring has been discovered. Compound 6 and its R-enantiomer 6a exhibited very potent oral activities in lowering the serum cholesterol in the animals.
iPF2α-III metabolism. First total synthesis of 2,3-dinor iPF2α-III, a primary β-oxidation metabolite

Abstract The total synthesis of a primary iPF 2α -III metabolite, namely dinor iPF 2α -III 8 , is described. The successful synthesis was finally accomplished by generating the carboxylic acid group at the end of the synthesis so as to avoid formation of an α,β-unsaturated carboxylic acid, which is prone to undergo side reactions
The Germline Variants rs61757955 and rs34988193 Are Predictive of Survival in Lower Grade Glioma Patients

Lower grade gliomas are invasive brain tumors that are difficult to completely resect neurosurgically. They often recur following resection and progress, resulting in death. Although previous studies have shown that specific germline variants increase the risk of tumor formation, no previous study has screened many germline variants to identify variants predictive of survival in patients with glioma. In this study, we present an approach to identify the small fraction of prognostic germline variants from the pool of over four million variants that we variant called in The Cancer Genome Atlas whole-exome sequencing and RNA sequencing datasets. We identified two germline variants that are predictive of poor patient outcomes by Cox regression, controlling for eleven covariates. rs61757955 is a germline variant found in the 3' UTR of GRB2 associated with increased KRAS signaling, CIC mutations, and 1p/19q codeletion. rs34988193 is a germline variant found in the tumor suppressor gene ANKDD1a that causes an amino acid change from lysine to glutamate. This variant was found to be predictive of poor prognosis in two independent lower grade glioma datasets and is predicted to be within the top 0.06% of deleterious mutations across the human genome. The wild-type residue is conserved in all 22 other species with a homologous protein. IMPLICATIONS: This is the first study presenting an approach to screening many germline variants to identify variants predictive of survival and our application of this methodology revealed the germline variants rs61757955 and rs34988193 as being predictive of survival in patients with lower grade glioma.
Coordination chemistry of cyclopentadienyl titanium carboxylates and related complexes

Abstract The coordination chemistry of cyclopentadienyltitanium carboxylate and its related complexes has been reviewed, with an emphasis on developments in the last decade. The syntheses of these coordination compounds can be carried out in different media, i.e. organic, aqueous or even two-phase systems. The aqueous-phase synthesis provides a complementary method for some compounds. By using di- and tetracarboxylic acids, the two-phase system has proven to be very effective for the preparation of novel multinuclear cyclic molecules and polymers, depending upon the reaction conditions. Thus, a variety of new complexes have been prepared and charactsrized. The molecular structures of most cyclopentadienyltitanium carboxylates have revealed a tetracoordinate, pseudo-tetrahedral coordination geometry. Pentaand higher coordinate complexes have also been reported recently and their structures determined by X-ray analyses. A commonly used criterion for distinguishing the M-OOCR coordination mode is the frequency difference between the asymmetric and symmetric OCO stretching modes (i.e. Δv=v(OCO)as-v(OCO)g), which is 200 cm−1 or more for monodentate bonding and up to 100 cm−1 for chelating bonding. The X-ray data are more supportive for determining the Ti-OOCR bonding nature, and these data have confirmed the monodentate nature of the two carboxylate ligands in Cp2Ti(OOCR)2 and that of the one carboxylate ligand in Cp2TiCl(OOCR) complexes. Titanocene carboxylates react with various amines to give amides, this is a new method using organometallics for peptide synthesis under severe conditions. The nuclear magnetic resonance data of meta- and para-substituted benzoate titanocenes of the type Cp2Ti(OOCC6H4X)2 have been analysed, showing good to excellent correlations between the chemical shifts and substituent parameters. The results also indicate a long-range interaction between the substituent X and the cyclopentadienyl ring carbon atoms. In the search for new antitumor agents, some titanocene carboxylates have been tested and found to be active against Ehrlich ascites tumor. In comparison with titanocene dihalides, for example, the hydrogenmaleinate complex is fairly soluble in water and the toxicity of titanocene trichloroacetate is particularly low.
POLYMER SUPPORTS IN SYNTHESIS

Diversity-oriented synthesis (DOS) is a term used by Schreiber (S. Schreiber, Science, 2000, 287, 1964) to describe the preparation of a large variety of highly functionalized molecules in a few steps, frequently involving combinatorial methods on polymer supports. Enantioselective 1,3-dipolar cycloaddition of azomethine ylides (see S. Kanemasa, Synless, 2002, 1371–1387) with electron-deficient olefins is a reaction method that produces stereochemical diversification by generating up to four tetrahedral centers on pyrolidine rings. The biological importance of pyrrolidines has stimulated the development of diasteroselective [3+2] azomethine ylide cycloadditions (J. Longmire, B. Wang, and Y. Zhang, J. Am. Chem. Soc., 2002, 124, 413400) and enantioselective variations employing chiral catalysts (K. A. Jorgensen, Angew. Chem. Int. Ed., 2002, 41, 4236). Now, Schreiber has developed the three-component, catalytic, asymmetric [3+2] cycloaddition of azomethine ylides for application in DOS employing solid phase ...
Host genetic variation in mucosal immunity pathways influences the upper airway microbiome.

The degree to which host genetic variation can modulate microbial communities in humans remains an open question. Here, we performed a genetic mapping study of the microbiome in two accessible upper airway sites, the nasopharynx and the nasal vestibule, during two seasons in 144 adult members of a founder population of European decent. We estimated the relative abundances (RAs) of genus level bacteria from 16S rRNA gene sequences and examined associations with 148,653 genetic variants (linkage disequilibrium [LD] r 2 < 0.5) selected from among all common variants discovered in genome sequences in this population. We identified 37 microbiome quantitative trait loci (mbQTLs) that showed evidence of association with the RAs of 22 genera (q < 0.05) and were enriched for genes in mucosal immunity pathways. The most significant association was between the RA of Dermacoccus (phylum Actinobacteria) and a variant 8 kb upstream of TINCR (rs117042385; p = 1.61 × 10−8; q = 0.002), a long non-coding RNA that binds to peptidoglycan recognition protein 3 (PGLYRP3) mRNA, a gene encoding a known antimicrobial protein. A second association was between a missense variant in PGLYRP4 (rs3006458) and the RA of an unclassified genus of family Micrococcaceae (phylum Actinobacteria) (p = 5.10 × 10−7; q = 0.032). Our findings provide evidence of host genetic influences on upper airway microbial composition in humans and implicate mucosal immunity genes in this relationship.
Proton affinities and gas-phase basicities: theoretical methods and structural effects

Abstract The inherent effects of molecular structure on acid–base behavior have been a topic of debate for over 30 years. Three of the models developed to probe these effects are reviewed in this article. Each model is described briefly and the results from its application to representative systems are summarized. The first model was proposed by Taft and coworkers and subdivides intrinsic substituent effects on proton-transfer equilibria into field effects, polarizability effects and resonance effects. Various techniques used to factor out the individual contributions of these effects are described. The importance of intramolecular hydrogen bonding in determining proton affinity is also discussed. The second model was proposed by Maksic and Vianello and separates the protonation process into three sequential steps in which an electron is removed from the base, the electron is captured by the proton, and a homolytic chemical bond is formed between the radical cation and hydrogen atom. The third model was proposed by Perez and coworkers and analyzes substituent effects on proton affinity with the aid of global and local descriptors of reactivity used in conjunction with the hard and soft acids and bases principle. Several of the composite methods designed to calculate accurate thermochemical data are also discussed briefly.
Silyl- and germyl-diazadiphosphetidines

Abstract Reaction of the 1,3,2,4-diazadiphosphetidine, trans-[C6H5N(H)P(S)NC6H5]2 with LiR (R = Me, n-Bu) followed by treatment of the resulting dianions with Me3SiCl and Me3GeBr produced trans-[C6H5N(R)P(S)NC6H5]2(R = Me3Si, 2; Me3Ge, 3). Substitution occurs without cis-trans isomerization or significant cleavage of the 1,3,2,4-diazadiphosphetidine ring. 2 and 3 have been characterized by spectral (1H and 31P NMR, IR, and MS) and elemental analytical data. Analogous reactions involving Me3SnCl yield mixtures containing [C6H5N(SnMe3)P(S)NC6H5]2 which could not be isolated or completely characterized.
Internalization of Erythrocyte Acylpeptide Hydrolase Is Required for Asexual Replication of Plasmodium falciparum.

ABSTRACT The human malaria parasite Plasmodium falciparum causes disease as it replicates within the host’s erythrocytes. We have found that an erythrocyte serine hydrolase, acylpeptide hydrolase (APEH), accumulates within developing asexual parasites. Internalization of APEH was associated with a proteolytic event that reduced the size of the catalytic polypeptide from 80 to 55 kDa. A triazole urea APEH inhibitor, termed AA74-1, was employed to characterize the role of parasite-internalized APEH. In cell lysates, AA74-1 was a potent and highly selective inhibitor of both host erythrocyte and parasite-internalized APEH. When added to cultures of ring-stage parasites, AA74-1 was a poor inhibitor of replication over one asexual replication cycle; however, its potency increased dramatically after a second cycle. This enhancement of potency was not abrogated by the addition of exogenous isopentenyl pyrophosphate, the sole essential product of apicoplast metabolism. High-potency inhibition of parasite growth could be effected by adding AA74-1 to schizont-stage parasites, which resulted in parasite death at the early trophozoite stage of the ensuing replication cycle. Analysis of APEH inhibition in intact cultured cells revealed that host erythrocyte APEH, but not the parasite-internalized APEH pool, was inhibited by exogenous AA74-1. Our data support a model for the mode of parasiticidal activity of AA74-1 whereby sustained inactivation of host erythrocyte APEH is required prior to merozoite invasion and during parasite asexual development. Together, these findings provide evidence for an essential catalytic role for parasite-internalized APEH. IMPORTANCE Nearly half a million deaths were attributed to malaria in 2017. Protozoan parasites of the genus Plasmodium cause disease in humans while replicating asexually within the host’s erythrocytes, with P. falciparum responsible for most of the mortality. Understanding how Plasmodium spp. have adapted to their unique host erythrocyte environment is important for developing malaria control strategies. Here, we demonstrate that P. falciparum coopts a host erythrocyte serine hydrolase termed acylpeptide hydrolase. By showing that the parasite requires acylpeptide hydrolase activity for replication, we expand our knowledge of host cell factors that contribute to robust parasite growth.
Cyclopropenation of Alkylidene Carbenes Derived from α-Silyl Ketones

A new cyclopropanation reaction involving Cα−Si bond insertion of alkylidene carbenes derived from α-silyl ketones has been developed. This unprecedented alkylidene carbene reactivity features excellent selectivity for insertion into Cα−Si bonds rather than insertion into Cγ−H bonds or addition to γ,δ-double or -triple bonds. The selectivity trend clearly indicates that the α-oxygen in the tether significantly promotes Cγ−H insertion, although the Cα−Si bond insertion still competes effectively.
Synthesis and reactivity of bicyclomycin C(3′) amines

The novel bicyclomycin C(3') tertiary amines 6-8 were prepared in which morpholine, N-acetylpiperazine, and N-carboethoxypiperazine were installed at the C(3') site in bicyclomycin (1), respectively. Previous attempts to synthesize bicyclomycin C(3') amines were unsuccessful. Compounds 68 were found to be more reactive than 1 in neutral and basic solutions. Under these conditions, a novel ring fragmentation process occurred to give a monosubstituted hydantoin (i.e., 15, 18, 19) and α-methylene-γ-butyrolactone (17). Pathways for the formation of hydantoins 15, 18, and 19 and butyrolactone 17 are proposed, and evidence is presented in support of these hypotheses. The potential significance of this ring fragmentation process in future drug design is discussed