SE(R)RS devices fabricated by a laser electrodispersion method

A novel laser electrodispersion (LE) technique was employed to deposit gold nanoparticles onto Si and SiO(x) surfaces. The LE technique combines laser ablation with cascade fission of liquid metal micro-drops, which results in the formation of nanoparticles upon rapid cooling. The shape and the size distribution of the Au nanoparticles prepared by LE depend on the nature of the support. Gold nanoparticles were also deposited in the channels of microreactors fabricated by wet etching of Si and used as SE(R)RS sensors. The influence of the nanoparticle surface density as well as of the nature of the substrate on the Raman response was studied. At an appropriate surface density of the deposited nanoparticles a significant enhancement of Raman signal was observed showing the possibility to create efficient SERS substrates. Application of microfluidic devices in surface enhanced Raman spectroscopy (SERS) in continuous-flow mode with sensor regeneration is described.     

Multicompartment polymer nanostructures with ratiometric dual-emission pH-sensitivity

Pyrazine-labeled multicompartment nanostructures are shown to exhibit enhanced pH-responsive blue-shifted fluorescence emission intensities compared to their simpler core-shell spherical analogs. An amphiphilic linear triblock terpolymer of ethylene oxide, N-acryloxysuccinimide, and styrene, PEO(45)-b-PNAS(105)-b-PS(45), which lacks significant incompatibility for the hydrophobic block segments and undergoes gradual hydrolysis of the NAS units, underwent supramolecular assembly in mixtures of organic solvent and water to afford multicompartment micelles (MCMs) with a narrow size distribution. The assembly process was followed over time and found to evolve from individual polymer nanodroplets containing internally phase segregated domains, of increasing definition, and ultimately to dissociate into discrete micelles. Upon covalent cross-linking of the MCMs with pH-insensitive pyrazine-based diamino cross-linkers, pH-responsive, photonic multicompartment nanostructures (MCNs) were produced. These MCNs exhibited significant enhancement of overall structural stability, in comparison with the MCMs, and internal structural tunability through the cross-linking chemistry. Meanwhile, the complex compartmentalized morphology exerted unique pH-responsive fluorescence dual-emission properties, indicating promise in ratiometric pH-sensing applications.     

Hydrogenolysis of palladium(II) hydroxide, phenoxide, and alkoxide complexes

A series of pincer ((tBu)PCP)Pd(II)-OR complexes ((tBu)PCP = 2,6-bis(CH(2)P(t)Bu(2))C(6)H(3), R = H, CH(3), C(6)H(5), CH(2)C(CH(3))(3), CH(2)CH(2)F, CH(2)CHF(2), CH(2)CF(3)) were synthesized to explore the generality of hydrogenolysis reactions of palladium-oxygen bonds. Hydrogenolysis of the Pd hydroxide complex to generate the Pd hydride complex and water was shown to be inhibited by formation of a water-bridged, hydrogen-bonded Pd(II) hydroxide dimer. The Pd alkoxide and aryloxide complexes exhibited more diverse reactivity. Depending on the characteristics of the -OR ligand (steric bulk, electron-donating ability, and/or the presence of β-hydrogen atoms), hydrogenolysis was complicated by hydrolysis by adventitious water, a lack of reactivity with hydrogen, or a competing dissociative β-hydride abstraction reaction pathway. Full selectivity for hydrogenolysis was observed with the partially fluorinated Pd(II) 2-fluoroethoxide complex. The wide range of Pd-OR substrates examined helps to clarify the variety of reaction pathways available to late-transition-metal alkoxides as well as the conditions necessary to tune the reactivity to hydrogenolysis, hydrolysis, or dissociative β-hydride abstraction.     

Development of proneurogenic, neuroprotective small molecules

Degeneration of the hippocampus is associated with Alzheimer's disease and occurs very early in the progression of the disease. Current options for treating the cognitive symptoms associated with Alzheimer's are inadequate, giving urgency to the search for novel therapeutic strategies. Pharmacologic agents that safely enhance hippocampal neurogenesis may provide new therapeutic approaches. We discovered the first synthetic molecule, named P7C3, which protects newborn neurons from apoptotic cell death, and thus promotes neurogenesis in mice and rats in the subgranular zone of the hippocampal dentate gyrus, the site of normal neurogenesis in adult mammals. We describe the results of a medicinal chemistry campaign to optimize the potency, toxicity profile, and stability of P7C3. Systematic variation of nearly every position of the lead compound revealed elements conducive toward increases in activity and regions subject to modification. We have discovered compounds that are orally available, nontoxic, stable in mice, rats, and cell culture, and capable of penetrating the blood-brain barrier. The most potent compounds are active at nanomolar concentrations. Finally, we have identified derivatives that may facilitate mode-of-action studies through affinity chromatography or photo-cross-linking.     

Aperiodicity in the near field of full-scale rotor blade tip vortices

Blade tip vortices are the dominant vortical structures of the helicopter flow field. The inherent complexity of the vortex dynamics has led to an increasing interest in full-scale in situ experiments, where the near field, closely behind the blade, is of particular interest, since measures of vortex control mostly target this initial stage of development. To examine the near field, three-component particle image velocimetry (PIV) measurements of blade tip vortices of a full-scale helicopter in simulated hover flight in ground effect were conducted. A feasible and robust evaluation procedure was developed to minimise the shortcomings of full-scale PIV applications, such as a moderate spatial resolution and an elevated measurement noise level. At vortex ages ranging from y_v=1^°\psi_{\rm v}=1^{\circ} to 30°, a pronounced aperiodicity and asymmetry of the vortex were observed in -sections perpendicular to the vortex axes. At y_v=1^°\psi_{\rm v}=1^{\circ}, a preferential orientation of the vortex was observed. For increasing wake age, vortex wandering increased while the asymmetry of the vortex cores decreased. The high level of aperiodicity and core asymmetry must be taken into account when considering phase-averaged vortex characteristics in the near wake region.     

Macrobicyclic cage amine ligands for copper radiopharmaceuticals: a single bivalent cage amine containing two Lys3-bombesin targeting peptides

The synthesis of new cage amine macrobicyclic ligands with pendent carboxylate functional groups designed for application in copper radiopharmaceuticals is described. Reaction of [Cu((NH(2))(2)sar)](2+) (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) with either succinic or glutaric anhydride results in selective acylation of the primary amine atoms of [Cu((NH(2))(2)sar)](2+) to give derivatives with either one or two aliphatic carboxylate functional groups separated from the cage amine framework by either a four- or five-atom linker. The Cu(II) serves to protect the secondary amine nitrogen atoms from acylation, and can be removed to give the free ligands. The newly appended carboxylate functional groups can be used as sites of attachment for cancer-targeting peptides such as Lys(3)-bombesin. The synthesis of the first dimeric sarcophagine-peptide conjugate, possessing two Lys(3)-bombesin peptides tethered to a single cage amine, is presented. This species has been radiolabeled with copper-64 at ambient temperature and there is minimal dissociation of Cu(II) from the conjugate even after two days of incubation in human serum.     

Headspace stir bar sorptive extraction-gas chromatography/mass spectrometry characterization of the diluted vapor phase of cigarette smoke delivered to an in vitro cell exposure chamber

Advanced smoke generation systems, such as the Borgwaldt RM20S^® smoking machine used in combination with the BAT exposure chamber, allow for the generation, dilution and delivery of fresh cigarette smoke to cell or tissue cultures for in vitro cell culture analyses. Recently, our group confirmed that the Borgwaldt RM20S^® is a reliable tool to generate and deliver repeatable and reproducible exposure concentrations of whole smoke to in vitro cultures [1]. However, the relationship between dose and diluted smoke components found within the exposure chamber has not been characterized. The current study focused on the development of a headspace stir bar sorptive extraction (HSSE) method to chemically characterize some of the vapor phase components of cigarette smoke generated by the Borgwaldt RM20S^® and collected within a cell culture exposure chamber. The method was based on passive sampling within the chamber by HSSE using a Twister™ stir bar. Following exposure, sorbed analytes were recovered using a thermal desorption unit and a cooled injection system coupled to gas chromatograph/mass spectrometry for identification and quantification. Using the HSSE method, sixteen compounds were identified. The desorption parameters were assessed using ten reference compounds and the following conditions led to the maximal response: desorption temperature of 200 °C for 2 min with cryofocussing temperature of −75 °C. During transfer of the stir bars to the thermal desorption system, significant losses of analytes were observed as a function of time; therefore, the exposure-to-desorption time interval was kept at the minimum of 10 ± 0.5 min. Repeatability of the HSSE method was assessed by monitoring five reference compounds present in the vapor phase (10.1–12.9% RSD) and n-butyl acetate, the internal standard (18.5% RSD). The smoke dilution precision was found to be 17.2, 6.2 and 11.7% RSD for exposure concentrations of 1, 2 and 5% (v/v) cigarette vapor phase in air, respectively. A linear response of analyte abundance was observed as a function of dilution. Extrapolation to 100% (v/v) cigarette vapor phase, i.e., undiluted smoke, gave yields for the five compounds ranging from 6 to 450 ng for 10 min exposure.     

Rapid quantification of pharmaceuticals and pesticides in passive samplers using ultra high performance liquid chromatography coupled to high resolution mass spectrometry

The presence of both pharmaceuticals and pesticides in the aquatic environment has become a well-known environmental issue during the last decade. An increasing demand however still exists for sensitive and reliable monitoring tools for these rather polar contaminants in the marine environment. In recent years, the great potential of passive samplers or equilibrium based sampling techniques for evaluation of the fate of these contaminants has been shown in literature. Therefore, we developed a new analytical method for the quantification of a high number of pharmaceuticals and pesticides in passive sampling devices. The analytical procedure consisted of extraction using 1:1 methanol/acetonitrile followed by detection with ultra-high performance liquid chromatography coupled to high resolution and high mass accuracy Orbitrap mass spectrometry. Validation of the analytical method resulted in limits of quantification and recoveries ranging between 0.2 and 20 ng per sampler sheet and between 87.9 and 105.2%, respectively. Determination of the sampler-water partition coefficients of all compounds demonstrated that several pharmaceuticals and most pesticides exert a high affinity for the polydimethylsiloxane passive samplers. Finally, the developed analytical methods were used to measure the time-weighted average (TWA) concentrations of the targeted pollutants in passive samplers, deployed at eight stations in the Belgian coastal zone. Propranolol, carbamazepine and seven pesticides were found to be very abundant in the passive samplers. These obtained long-term and large-scale TWA concentrations will contribute in assessing the environmental and human health risk of these emerging pollutants.     

Families of Spectral Sets for Bernoulli Convolutions

We study the harmonic analysis of Bernoulli measures μ _λ , a one-parameter family of compactly supported Borel probability measures on the real line. The parameter λ is a fixed number in the open interval (0,1). The measures μ _λ may be understood in any one of the following three equivalent ways: as infinite convolution measures of a two-point probability distribution; as the distribution of a random power series; or as an iterated function system (IFS) equilibrium measure determined by the two transformations λ(x±1). For a given λ, we consider the harmonic analysis in the sense of Fourier series in the Hilbert space L ²(μ _λ ). For L ²(μ _λ ) to have infinite families of orthogonal complex exponential functions e ^2πis(⋅), it is known that λ must be a rational number of the form \fracm2n\frac{m}{2n}, where m is odd. We show that L²(m_\frac12n)L^{2}(\mu_{\frac{1}{2n}}) has a variety of Fourier bases; i.e. orthonormal bases of exponential functions. For some other rational values of λ, we exhibit maximal Fourier families that are not orthonormal bases.     

The n �� n KdV hierarchy

We introduce two new soliton hierarchies that are generalizations of the KdV hierarchy. Our hierarchies are restrictions of the AKNS n × n hierarchy coming from two unusual splittings of the loop algebra. These splittings come from automorphisms of the loop algebra instead of automorphisms of sl (n, \mathbbC){sl (n, \mathbb{C})} . The flows in the hierarchy include systems of coupled nonlinear Schr?dinger equations. Since they are constructed from a Lie algebra splitting, the general method gives formal inverse scattering, bi-Hamiltonian structures, commuting flows, and B?cklund transformations for these hierarchies.