Coherent Raman scanning fiber endoscopy

Coherent Raman scattering methods allow for label-free imaging of tissue with chemical contrast and high spatial and temporal resolution. However, their imaging depth in scattering tissue is limited to less than 1 mm, requiring the development of endoscopes to obtain images deep inside the body. Here, we describe a coherent Raman endoscope that provides stimulated Raman scattering images at seven frames per second using a miniaturized fiber scanner, a custom-designed objective lens, and an optimized scheme for collection of scattered light from the tissue. We characterize the system and demonstrate chemical selectivity in mouse tissue images.     

Mapping the Stability and Curvature of Emulsions of H2O and Supercritical CO2 with Interfacial Tension Measurements

The stability and curvature of emulsions of H₂O and CO₂ are reported and analyzed in terms of measurements of interfacial tension versus formulation variables, including salinity, CO₂ density, temperature and pH. Among the surfactants studied are, quaternary ammonium cationic ones with perfluoropolyether tails, block copolymer ionomers and a poly (hydroxyethyl methacrylate) with polydimethylsiloxane tails, and a nonionic ethylene oxide surfactant with a fluoroalkane tail. The interfacial tension measurements were made at surfactant concentrations from 0.05 to 1.0 wt% with a variable-volume pendant drop tensiometer up to 345 bar and 363°K. As a formulation variable was varied, the system reached a balanced state characterized by a minimum in interfacial tension, a loss in emulsion stability and in some cases an inversion from a W/C to C/W emulsion. Here the Marangoni-Gibbs stabilization weakens, and also it becomes easy to bend and rupture the surfactant monolayer, causing coalescence. Except in the case of the nonionic fluorinated surfactant C₈F₁₇—SO₂NEt-(CH₂CH₂O)_12–14CH₃, the crossover from the CO₂-continuous (W/C) to the H₂O-continuous (C/W) emulsion occurred abruptly due to clouding of the surfactant out of the CO₂ phase. For PFPE-TMAA, the plot of γ versus surfactant concentration revealed both pre-micellar aggregates and a critical micro emulsion, each of which was dependent on salinity.     

Thermogravimetric Analysis of Vinyl Chloride/Acrylonitrile Copolymers

The dehydrohalogenation of several alternating and random vinyl chloride/acrylonitrile copolymers was characterized by thermogravimetry. The polymers were made in solution, and the conversions were kept below 5% to insure uniform sequence distributions. Hydrogen chloride was generated within a relatively narrow temperature range somewhere between 200 and 300°C depending on the sequence distribution, relative viscosity, and composition. The weight-loss during the dehydrohalogenation could be attributed completely to the hydrogen chloride available in the copolymer. Alternating copolymers were significantly more stable than random copolymers were significantly more stable than random copolymers at the same relative viscosity. For a given sequence distribution or composition, stability decreased with decreasing relative viscosity. The stability decreased as acrylonitrile content was increased from 23 to 57%.

The thermogravimetric analyzer was interfaced with a digital computer. The digitized data were smoothed and differentiated by convoluted integers. The differentiated data provided rates for a qualitative discussion of dehydrohalogenation kinetics.     

Effector Kinase Coupling Enables High-Throughput Screens for Direct HIV-1 Nef Antagonists with Antiretroviral Activity

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Highlights? Nef is a critical HIV virulence factor lacking biochemical activity amenable to HTS ? HTS for inhibitors of Nef-mediated Hck kinase activation identified Nef antagonists ? Hit compound B9 blocks Nef-dependent HIV replication with submicromolar potency ? B9 binds directly to purified HIV Nef in vitro and blocks Nef dimerization in cells     

Norm duality and the cross norm criteria for quantum entanglement

We use duality techniques to prove and generalize the cross norm and computable cross norm criteria for separability of quantum states. While the original proof of the cross norm criterion is long and involved, our new proof is short and elementary. Furthermore, our proof generalizes naturally to arbitrary Schmidt number. We also use these techniques to generalize the computable cross norm criterion to arbitrary Schmidt number and prove some results of independent interest along the way.     

Billion‐Fold Enhancement in Sensitivity of Nuclear Magnetic Resonance Spectroscopy for Magnesium Ions in Solution

β‐nuclear magnetic resonance (NMR) spectroscopy is highly sensitive compared to conventional NMR spectroscopy, and may be applied for several elements across the periodic table. β‐NMR has previously been successfully applied in the fields of nuclear and solid‐state physics. In this work, β‐NMR is applied, for the first time, to record an NMR spectrum for a species in solution. ³¹Mg β‐NMR spectra are measured for as few as 10⁷ magnesium ions in ionic liquid (EMIM‐Ac) within minutes, as a prototypical test case. Resonances are observed at 3882.9 and 3887.2 kHz in an external field of 0.3 T. The key achievement of the current work is to demonstrate that β‐NMR is applicable for the analysis of species in solution, and thus represents a novel spectroscopic technique for use in general chemistry and potentially in biochemistry.     

A van der Waals density functional theory study of poly(vinylidene difluoride) crystalline phases

Ferroelectric polymers, such as poly(vinylidene difluoride) (PVDF), have many potential applications in flexible electronic devices. PVDF has six experimentally observed polymorphs, three of which are ferroelectric. In this work we use density functional theory to investigate the structural properties, energetics and polarisation of the stable α-phase, its ferroelectric analogue, the δ-phase, and the β-phase, which has the best ferroelectric properties. The results from a variety of exchange and correlation functionals were compared and it was found that van der Waals (vdW) interactions have an important effect on the calculated crystal structures and energetics, with the vdW-DF functional giving the best agreement with experimental lattice parameters. The spontaneous polarisation was found to strongly correlate with the unit cell volumes, which depend on the functional used. While the relative phase energies were not strongly dependent on the functional, the cohesive energies were significantly underestimated using the PBE functional. The inclusion of vdW interactions is, therefore, important to obtain the correct lattice structures, polarisation and energetics of PVDF polymorphs.     

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.     

A formal enantioselective acetate Mannich reaction: the nitro functional group as a traceless agent for activation and enantiocontrol in the synthesis of beta-amino acids

A two-step procedure involving the enantioselective addition of alpha-nitro esters to imines, followed by reductive denitration, provides a convenient new enantioselective synthesis of beta-amino acids. Specifically, beta-phenyl alanine derivatives with up to 98% ee are formed in good yield (64-88%) over two steps. The utility of the approach is demonstrated through the first enantioselective synthesis of the key beta-amino acid of (+)-chaenorhine.     

Covalent inhibitors of human monoacylglycerol lipase: ligand-assisted characterization of the catalytic site by mass spectrometry and mutational analysis

The active site of recombinant hexa-histidine-tagged human monoacylglycerol lipase (hMGL) is characterized by mass spectrometry using the inhibitors 5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide (AM6701), and N-arachidonylmaleimide (NAM) as probes. Carbamylation of Ser(129) by AM6701 in the putative hMGL catalytic triad demonstrates this residue's essential role in catalysis. Partial NAM alkylation of hMGL cysteine residues 215 and/or 249 was sufficient to achieve approximately 80% enzyme inhibition. Although Cys(215) and/or Cys(249) mutations to alanine(s) did not affect hMGL hydrolytic activity as compared with nonmutated hMGL, the C215A displayed heightened NAM sensitivity, whereas the C249A evidenced reduced NAM sensitivity. These data conclusively demonstrate a sulfhydryl-based mechanism for NAM inhibition of hMGL in which Cys(249) is of paramount importance. Identification of amino acids critical to the catalytic activity and pharmacological modulation of hMGL informs the design of selective MGL inhibitors as potential drugs.