Elucidation of the natural artemisinin decomposition route upon iron interaction: a fine electronic redistribution promotes reactivity

The conformational analysis of artemisinin by molecular dynamics and quantum chemistry calculations revealed the existence of seven energy minima with specific interconversion pathways. Among the seven conformers, only , and were able to undergo bond rearrangements upon Fe(2+) interaction. These rearrangements were due to a peculiar puckering of the trioxane ring that brings its three oxygen atoms in an ideal geometrical position for interacting with Fe(2+) ions, promoting an electronic redistribution in the molecule. A rapid molecule rearrangement led to a stable energy minimum structure with an additional ring that is similar to a plant metabolite. Our results suggest an alternative pathway for generating toxic radical chemical species for the malaria parasite, where artemisinin is not toxic by itself but rather is an intermediate for molecular partners that generate radical structures deleterious for the parasite proteins, after electron transfers from the Fe(2+)/artemisinin complex.     

Effects of conjugation length and resonance enhancement on two-photon absorption in phenylene-vinylene oligomers

Two-photon excitation spectra have been recorded over the large spectral range of 540-1000 nm for five phenylene-vinylene oligomers that differ in the length of the conjugated pi system. The significant changes observed in the two-photon excitation spectra and absorption cross sections as a function of this systematic change in the chromophore are discussed in light of (1) the corresponding one-photon absorption spectra and (2) high-level density functional response theory calculations performed on analogues of these systems. The results obtained illustrate one way to exploit parameters that influence nonlinear optical properties in large organic molecules. Specifically, data are provided to indicate that when the frequency of the laser used in the two-photon experiment is nearly-resonant with an allowed one-photon transition, significant increases in the two-photon absorption cross section can be realized. This phenomenon of the so-called resonance enhancement allows for greater control in obtaining an optimal response when using existing two-photon chromophores, and provides a much-needed guide for the systematic development and efficient use of two-photon singlet oxygen sensitizers.     

Microfluidic platform for real-time signaling analysis of multiple single T cells in parallel

Deciphering the signaling pathways that govern stimulation of na?ve CD4+ T helper cells by antigen-presenting cells via formation of the immunological synapse is key to a fundamental understanding of the progression of successful adaptive immune response. The study of T cell-APC interactions in vitro is challenging, however, due to the difficulty of tracking individual, non-adherent cell pairs over time. Studying single cell dynamics over time reveals rare, but critical, signaling events that might be averaged out in bulk experiments, but these less common events are undoubtedly important for an integrated understanding of a cellular response to its microenvironment. We describe a novel application of microfluidic technology that overcomes many limitations of conventional cell culture and enables the study of hundreds of passively sequestered hematopoietic cells for extended periods of time. This microfluidic cell trap device consists of 440 18 micromx18 micromx10 microm PDMS, bucket-like structures opposing the direction of flow which serve as corrals for cells as they pass through the cell trap region. Cell viability analysis revealed that more than 70% of na?ve CD4+ T cells (TN), held in place using only hydrodynamic forces, subsequently remain viable for 24 hours. Cytosolic calcium transients were successfully induced in TN cells following introduction of chemical, antibody, or cellular forms of stimulation. Statistical analysis of TN cells from a single stimulation experiment reveals the power of this platform to distinguish different calcium response patterns, an ability that might be utilized to characterize T cell signaling states in a given population. Finally, we investigate in real time contact- and non-contact-based interactions between primary T cells and dendritic cells, two main participants in the formation of the immunological synapse. Utilizing the microfluidic traps in a daisy-chain configuration allowed us to observe calcium transients in TN cells exposed only to media conditioned by secretions of lipopolysaccharide-matured dendritic cells, an event which is easily missed in conventional cell culture where large media-to-cell ratios dilute cellular products. Further investigation into this intercellular signaling event indicated that LPS-matured dendritic cells, in the absence of antigenic stimulation, secrete chemical signals that induce calcium transients in T(N) cells. While the stimulating factor(s) produced by the mature dendritic cells remains to be identified, this report illustrates the utility of these microfluidic cell traps for analyzing arrays of individual suspension cells over time and probing both contact-based and intercellular signaling events between one or more cell populations.     

Rhodium-Catalyzed Asymmetric Arylation-Induced Glycolate Aldol Additions of Silyl Glyoxylates

(Diene)Rh(I) complexes catalyze the stereoselective three-component coupling of silyl glyoxylates, arylboronic acids, and aldehydes to give glycolate aldol products. The participation of Rh-alkoxides in the requisite Brook rearrangement was established through two component Rh-catalyzed couplings of silyl glyoxylates with ArB(OH)₂ to give silyl-protected mandelate derivatives. The intermediacy of a chiral Rh-enolate was inferred through enantioselective protonation using a chiral Rh-catalyst. Diastereoselective three-component couplings with aldehydes as terminating electrophiles to give racemic products were best achieved with a bulky aryl ester on the silyl glyoxylate reagent. Optimal enantioselective couplings were carried out with the tert-butyl ester variant using an anisole-derived enantiopure tricyclo[3.2.2.0^2,4]nonadiene ligand.     

Searching the Chemical Space of Bicyclic Dienes for Molecular Solar Thermal Energy Storage Candidates

Photoswitches are molecular systems that are chemically transformed subsequent to interaction with light and they find potential application in many new technologies. The design and discovery of photoswitch candidates require intricate molecular engineering of a range of properties to optimize a candidate to a specific applications, a task which can be tackled efficiently using quantum chemical screening procedures. In this paper, we perform a large scale screening of approximately half a million bicyclic diene photoswitches in the context of molecular solar thermal energy storage using ab initio quantum chemical methods. We further device an efficient strategy for scoring the systems based on their predicted solar energy conversion efficiency and elucidate potential pitfalls of this approach. Our search through the chemical space of bicyclic dienes reveals systems with unprecedented solar energy conversion efficiencies and storage densities that show promising design guidelines for next generation molecular solar thermal energy storage systems.     

Sparse Partially Linear Additive Models

The generalized partially linear additive model (GPLAM) is a flexible and interpretable approach to building predictive models. It combines features in an additive manner, allowing each to have either a linear or nonlinear effect on the response. However, the choice of which features to treat as linear or nonlinear is typically assumed known. Thus, to make a GPLAM a viable approach in situations in which little is known a priori about the features, one must overcome two primary model selection challenges: deciding which features to include in the model and determining which of these features to treat nonlinearly. We introduce the sparse partially linear additive model (SPLAM), which combines model fitting and both of these model selection challenges into a single convex optimization problem. SPLAM provides a bridge between the lasso and sparse additive models. Through a statistical oracle inequality and thorough simulation, we demonstrate that SPLAM can outperform other methods across a broad spectrum of statistical regimes, including the high-dimensional (p ? N) setting. We develop efficient algorithms that are applied to real datasets with half a million samples and over 45,000 features with excellent predictive performance. Supplementary materials for this article are available online.     

Reevaluating the conventional approach for analyzing spectroscopic ellipsometry psi/delta versus time data. Additional statistical rigor may often be appropriate

A standard approach for confirming the stability of thin films consists of probing them over an extended period of time by spectroscopic ellipsometry (SE) and plotting the resulting psi (Ψ) and delta (Δ) values versus time at a few selected wavelengths across the spectral range. In general, if Ψ and Δ remain constant with time, or essentially constant, the material is deemed to be stable. Here, we suggest that in addition to this ‘eyeball’ approach, a statistical analysis of the data may often be appropriate. In particular, we reevaluate a set of Ψ/Δ versus time data from a sputtered bismuth–tellurium–selenium film that appear to remain essentially constant by the traditional approach, subjecting it to a distance analysis, a principal components analysis, and a cluster analysis. The application of these statistical tools, especially to range‐selected data (300–989 nm), reveals previously unobserved changes, suggesting that either the film in question or the analytical approach itself had changed during the course of the measurements. Weighted distance formulas for Ψ and Δ were also applied so that the data did not need to be range selected for the key effects to be observed. The distance approach was similarly applied (i) to a set of SE data from a thin carbon film, which revealed consistent changes in the material that were not apparent in the standard approach, and (ii) to samples that were deliberately contaminated or improperly measured. Thus, we recommend a more rigorous, statistical approach to the analysis of SE Ψ/Δ versus time data. Copyright © 2016 John Wiley & Sons, Ltd.     

Benchmarking compressed sensing,super‐resolution,and filter diagonalization

Signal processing techniques have been developed that use different strategies to bypass the Nyquist sampling theorem in order to recover more information than a traditional discrete Fourier transform. Here we examine three such methods: filter diagonalization, compressed sensing, and super‐resolution. We apply them to a broad range of signal forms commonly found in science and engineering in order to discover when and how each method can be used most profitably. We find that filter diagonalization provides the best results for Lorentzian signals, while compressed sensing and super‐resolution perform better for arbitrary signals. © 2016 Wiley Periodicals, Inc.     

Response to: “Comment on benchmarking compressed sensing,super‐resolution,and filter diagonalization”

In light of a recent comment by Vladimir Mandelshtam, we provide a brief, theoretically motivated, justification of our methodology. We show that our error metric provides a valid lower bound for the parameter estimation error through both exact calculations and numerical examples. Additionally, we prove the validity of Parseval?s identity.