Enantioselective Organocatalytic Singly Occupied Molecular Orbital Activation: The Enantioselective α-Enolation of Aldehydes

The first enantioselective organocatalytic α-enolation of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Chiral secondary amines react with aldehydes to form transient enamines that undergo selective one-electron oxidation to generate electrophilic radical cations. These SOMO-activated radical cations are susceptible to attack by ketone-derived enol silanes, rendering α-substituted-γ-ketoaldehyde products with uniformly high levels of asymmetric induction. Wide latitude in both the aldehyde and enolsilane component is readily accommodated, allowing generic access to a diverse assortment of enantioenriched 1,4-dicarbonyl compounds. This report highlights the potential of SOMO catalysis to enable the development of entirely new classes of asymmetric reactions that have no traditional catalytic equivalents

An Examination of Contextual and Organizational Factors Influencing Police Use of Force: A Multilevel Model

The current study attempts to bridge this gap in research between contextual factors and police use of force. It also deepens our understandings of the association between organizational factors and use of force by incorporating police training into the analytical model. Finally, this study expands prior research by including multiple police agencies in the sample, thus producing research findings that can be more easily generalized

Sex differences in atheroma burden and endothelial function in patients with early coronary atherosclerosis

Aims Women and men have different clinical presentations and outcomes in coronary artery disease (CAD). We tested the hypothesis that sex differences may influence coronary atherosclerotic burden and coronary endothelial function before development of obstructive CAD. Methods and results A total of 142 patients (53 men, 89 women; mean ± SD age, 49.3 ± 11.7 years) with early CAD simultaneously underwent intravascular ultrasonography and coronary endothelial function assessment. Atheroma burden in the left main and proximal left anterior descending (LAD) arteries was significantly greater in men than women (median, 23.0% vs. 14.1%, P = 0.002; median, 40.1% vs. 29.3%, P = 0.001, respectively). Atheroma eccentricity in the proximal LAD artery was significantly higher in men than women (median, 0.89 vs. 0.80, P = 0.04). The length of the coronary segments with endothelial dysfunction was significantly longer in men than women (median, 39.2 vs. 11.1 mm, P = 0.002). In contrast, maximal coronary flow reserve was significantly lower in women than men (2.80 vs. 3.30, P < 0.001). Sex was an independent predictor of atheroma burden in the left main and proximal LAD arteries (both P < 0.05) by multivariate analysis. Conclusion Men have greater atheroma burden, more eccentric atheroma, and more diffuse epicardial endothelial dysfunction than women. These results suggest that men have more severe structural and functional abnormalities in epicardial coronary arteries than women, even in patients with early atherosclerosis, which may result in the higher incidence rates of CAD and ST-segment myocardial infarction in men than wome

Profiling translatomes of discrete cell populations resolves altered cellular priorities during hypoxia in Arabidopsis

Multicellular organs are composed of distinct cell types with unique assemblages of translated mRNAs. Here, ribosome-associated mRNAs were immunopurified from specific cell populations of intact seedlings using Arabidopsis thaliana lines expressing a FLAG-epitope tagged ribosomal protein L18 (FLAG-RPL18) via developmentally regulated promoters. The profiling of mRNAs in ribosome complexes, referred to as the translatome, identified differentially expressed mRNAs in 21 cell populations defined by cell-specific expression of FLAG-RPL18. Phloem companion cells of the root and shoot had the most distinctive translatomes. When seedlings were exposed to a brief period of hypoxia, a pronounced reprioritization of mRNA enrichment in the cell-specific translatomes occurred, including a ubiquitous rise in 49 mRNAs encoding transcription factors, signaling proteins, anaerobic metabolism enzymes, and uncharacterized proteins. Translatome profiling also exposed an intricate molecular signature of transcription factor (TF) family member mRNAs that was markedly reconfigured by hypoxia at global and cell-specific levels. In addition to the demonstration of the complexity and plasticity of cell-specific populations of ribosome-associated mRNAs, this study provides an in silico dataset for recognition of differentially expressed genes at the cell-, region-, and organ-specific levels.Instituto de Biotecnologia y Biologia Molecula

Quasi-three-level Model Applied to Measured Spectra of Nonlinear Absorption and Refraction in Organic Molecules

Materials with a large nonlinear refractive index (2) and relatively small linear and nonlinear absorption losses, namely, two-photon absorption (2PA, of coefficient 2), have long been sought after for applications such as all-optical switching (AOS). Here we experimentally determine the linear and 2PA properties of several organic molecules, which we approximate as centrosymmetric, and use a simplified essential-state model (quasi-three-level model) to predict the dispersion of 2. We then compare these predictions with experimental measurements of 2 and find good agreement. Here “quasi”-three-level means using a single one-photon allowed intermediate state and multiple (here two) two-photon allowed states. This also allows predictions of the figure-of-merit (FOM), defined as the ratio of nonlinear refractive phase shift to the 2PA fractional loss, that determines the viability for such molecules to be used in device applications. The model predicts that the optimized wavelength range for a large FOM lies near the short wavelength linear absorption edge for cyanine-like dyes where the magnitude of 2 is quite large. However, 2PA bands lying close to the linear absorption edge in certain classes of molecules can greatly reduce this FOM. We identify two molecules having a large FOM for AOS. We note that the FOM is often defined as the ratio of real to imaginary parts of the third-order susceptibility ((3)) with multiple processes leading to both components. As explained later in this paper, such definitions require care to only include the 2PA contribution to the imaginary part of (3) in regions of transparency.Abstract © 2016 Optical Society of Americ

Modified chitosan for effective renal delivery of siRNA to treat acute kidney injury.

Acute kidney injury (AKI) is characterized by a sudden decrease in renal function and impacts growing number of people worldwide. RNA interference (RNAi) showed potential to treat diseases with no or limited conventional therapies, including AKI. Suitable carriers are needed to protect and selectively deliver RNAi to target cells to fully explore this therapeutic modality. Here, we report on the synthesis of chitosan modified with α-cyclam-p-toluic acid (C-CS) as a novel siRNA carrier for targeted delivery to injured kidneys. We demonstrate that conjugation of the α-cyclam-p-toluic acid to chitosan imparts the C-CS polymer with targeting and antagonistic properties to cells overexpressing chemokine receptor CXCR4. In contrast, the parent α-cyclam-p-toluic acid showed no such properties. Self-assembled C-CS/siRNA nanoparticles rapidly accumulate in the injured kidneys and show long retention in renal tubules. Apoptosis and metabolic and inflammatory pathways induced by p53 are important pathological mechanisms in the development of AKI. Nanoparticles with siRNA against p53 (sip53) were formulated and intravenously injected for attenuation of IRI-AKI. Due to the favorable accumulation in injured kidneys, the treatment with C-CS/sip53 decreased renal injury, extent of renal apoptosis, macrophage and neutrophil infiltration, and improved renal function. Overall, our study suggests that C-CS/siRNA nanoparticles have the potential to effectively accumulate and deliver therapeutic siRNAs to injured kidneys through CXCR4 binding, providing a novel way for AKI therapy

Parallel Tempering: Theory, Applications, and New Perspectives

We review the history of the parallel tempering simulation method. From its origins in data analysis, the parallel tempering method has become a standard workhorse of physiochemical simulations. We discuss the theory behind the method and its various generalizations. We mention a selected set of the many applications that have become possible with the introduction of parallel tempering and we suggest several promising avenues for future research.Comment: 21 pages, 4 figure