Liquid crystalline oligofluorenes and their derivatives

Homo-oligofluorenes (OFn), polyfluorenes (PF2/6) and oligofluorenes with one fluorenenone group in the center (OFnK) were synthesized. They were used as model compounds to understand of the structure-property relationships of polyfluorenes and the origin of the green emission in the photoluminescence (after photooxidation of the PFs) and the electroluminescence (EL) spectra. The electronic, electrochemical properties, thermal behavior, supramolecular self-assembly, and photophysical properties of OFn, PF2/6 and OFnK were investigated. Oligofluorenes with 2-ethylhexyl side chain (OF2-OF7) from the dimer up to the heptamer were prepared by a series of stepwise transition metal mediated Suzuki and Yamamoto coupling reactions. Polyfluorene was synthesized by Yamamoto coupling of 2,7-dibromo-9,9-bis(2-ethylhexyl)fluorene. Oligofluorenes with one fluorenone group in the center (OF3K, OF5K, OF7K) were prepared by Suzuki coupling between the monoboronic fluorenyl monomer, dimer, trimer and 2, 7-dibromofluorenone. The electrochemical and electronic properties of homo-oligofluorenes (OFn) were systematically studied by several combined techniques such as cyclic voltammetry, differential pulse voltammetry, UV-vis absorption spectroscopy, steady and time-resolved fluorescence spectroscopy. It was found that the oligofluorenes behave like classical conjugated oligomers, i.e., with the increase of the chain-length, the corresponding oxidation potential, the absorption and emission maximum, ionization potential, electron affinity, band gap and the photoluminescence lifetime displayed a very good linear relation with the reciprocal number of the fluorene units (1/n). The extrapolation of these linear relations to infinite chain length predicted the electrochemical and electronic properties of the corresponding polyfluorenes. The thermal behavior, single-crystal structure and supramolecular packing, alignment properties, and molecular dynamics of the homo-oligofluorenes (OFn) up to the polymer were studied using techniques such as TGA, DSC, WAXS, POM and DS. The OFn from tetramer to heptamer show a smectic liquid crystalline phase with clearly defined isotropization temperature. The oligomers do show a glass transition which exhibits n-1 dependence and allows extrapolation to a hypothetical glass transition of the polymer at around 64 °C. A smectic packing and helix-like conformation for the oligofluorenes from tetramer to heptamer was supported by WAXS experiments, simulation, and single-crystal structure of some oligofluorene derivatives. Oligofluorenes were aligned more easily than the corresponding polymer, and the alignability increased with the molecular length from tetramer to heptamer. The molecular dynamics in a series of oligofluorenes up to the polymer was studied using dielectric spectroscopy. The photophysical properties of OFn and PF2/6 were investigated by the steady-state spectra (UV-vis absorption and fluorescence spectra) and time-resolved fluorescence spectra both in solution and thin film. The time-resolved fluorescence spectra of the oligofluorenes were measured by streak camera and gate detection technique. The lifetime of the oligofluorenes decreased with the extension of the chain-length. No green emission was observed in CW, prompt and delayed fluorescence for oligofluorenes in m-THF and film at RT and 77K. Phosphorescence was observed for oligofluorenes in frozen dilute m-THF solution at 77K and its lifetime increased with length of oligofluorenes. A linear relation was obtained for triplet energy and singlet energy as a function of the reciprocal degree of polymerization, and the singlet-triplet energy gap (S1-T1) was found to decrease with the increase of degree of polymerization. Oligofluorenes with one fluorenone unit at the center were used as model compounds to understand the origin of the low-energy (“green”) emission band in the photoluminescence and electroluminescence spectra of polyfluorenes. Their electrochemical properties were investigated by CV, and the ionization potential (Ip) and electron affinity (Ea) were calculated from the onset of oxidation and reduction of OFnK. The photophysical properties of OFnK were studied in dilute solution and thin film by steady-state spectra and time-resolved fluorescence spectra. A strong green emission accompanied with a weak blue emission were obtained in solution and only green emission was observed on film. The strong green emission of OFnK suggested that rapid energy transfer takes place from higher energy sites (fluorene segments) to lower energy sites (fluorenone unit) prior to the radiative decay of the excited species. The fluorescence spectra of OFnK also showed solvatochromism. Monoexponential decay behaviour was observed by time-resolved fluorescence measurements. In addition, the site-selective excitation and concentration dependence of the fluorescence spectra were investigated. The ratio of green and blue emission band intensities increases with the increase of the concentration. The observed strong concentration dependence of the green emission band in solution suggests that increased interchain interactions among the fluorenone-containing oligofluorene chain enhanced the emission from the fluorenone defects at higher concentration. On the other hand, the mono-exponential decay behaviour and power dependence were not influenced significantly by the concentration. We have ruled out the possibility that the green emission band originates from aggregates or excimer formation. Energy transfer was further investigated using a model system of a polyfluorene doped by OFnK. Förster-type energy transfer took place from PF2/6 to OFnK, and the energy transfer efficiency increased with increasing of the concentration of OFnK. Efficient funneling of excitation energy from the high-energy fluorene segments to the low-energy fluorenone defects results from energy migration by hopping of excitations along a single polymer chain until they are trapped on the fluorenone defects on that chain or transferred onto neighbouring chains by Förster-type interchain energy transfer process. These results imply that the red-shifted emission in polyfluorenes can originate from (usually undesirable) keto groups at the bridging carbon atoms-especially if the samples have been subject to photo- or electro-oxidation or if fluorenone units are present due to an improper purification of the monomers prior to polymerization.

New discotic liquid crystals based on large polycyclic aromatic hydrocarbons as materials for molecular electronics

A series of new columnar discotic liquid crystalline materials based on the superphenalene (C96) core has been synthesized by oxidative cyclodehydrogenation with iron(III) chloride of suitable three-dimensional oligophenylene precursors. These compounds were investigated by means of differential scanning calorimetry (DSC), polarized optical microscopy (POM) and wide angle X-ray scattering (WAXS), and showed highly ordered supramolecular arrays and mesophase behavior over a broad temperature range. Good solubility, through the introduction of long alkyl chains, and the fact that these new superphenalene derivatives were found to be liquid crystalline at room temperature enabled the formation of highly ordered films (using the zone-casting technique), a requirement for application in organic electronic devices. The one-dimensional, intracolumnar charge carrier mobilities of superphenalene derivatives were determined using the pulse-radiolysis time-resolved microwave conductivity technique (PR-TRMC). Electrical properties of different C96-C12 architectures on mica surfaces were examined by using Electrostatic Force Microscopy (EFM) and Kelvin Probe Force Microscopy (KPFM). Hexa-peri-hexabenzocoronene (C42) derivatives substituted at the periphery with six branched alkyl ether chains were also synthesized. It was found that the introduction of ether groups within the side chains enhances the affinity of the discotic molecules towards polar surfaces, resulting in homeotropic self-assembly (as shown by POM and 2D-WAXS) when the compounds are processed from the isotropic state between two surfaces. A new, insoluble, superphenalene building block bearing six reactive sites was prepared, and was further used for the preparation of dendronized superphenalenes with bulky dendritic substituents around the core. UV/Vis and fluorescence experiments suggest reduced π-π stacking of the superphenalene cores as a result of steric hindrance between the peripheral dendritic units. A new family of graphitic molecules with partial ”zig-zag” periphery has been established. The incorporation of ”zig-zag” edges was shown to have a strong influence on the electronic properties of the new molecules (as studied by solution and solid-state UV/Vis, and fluorescence spectroscopy), leading to a significant bathochromic shift with respect to the parent PAHs (C42 and C96). The reactivity of the additional double bonds was examined. The attachment of long alkyl chains to a ”zig-zag” superphenalene core afforded a new, processable, liquid crystalline material.

The bursting behavior of gas slugs: laboratory and analytical insights into Strombolian volcanic eruptions.

The aim of this thesis is to study how explosive behavior and geophysical signals in a volcanic conduit are related to the development of overpressure in slug-driven eruptions. A first suite of laboratory experiments of gas slugs ascending in analogue conduits was performed. Slugs ascended into a range of analogue liquids and conduit diameters to allow proper scaling to the natural volcanoes. The geometrical variation of the slug in response to the explored variables was parameterised. Volume of gas slug and rheology of the liquid phase revealed the key parameters in controlling slug overpressure at bursting. Founded on these results, a theoretical model to calculate burst overpressure for slug-driven eruptions was developed. The dimensionless approach adopted allowed to apply the model to predict bursting pressure of slugs at Stromboli. Comparison of predicted values with measured data from Stromboli volcano showed that the model can explain the entire spectrum of observed eruptive styles at Stromboli – from low-energy puffing, through normal Strombolian eruptions, up to paroxysmal explosions – as manifestations of a single underlying physical process. Finally, another suite of laboratory experiments was performed to observe oscillatory pressure and forces variations generated during the expansion and bursting of gas slugs ascending in a conduit. Two end-member boundary conditions were imposed at the base of the pipe, simulating slug ascent in closed base (zero magma flux) and open base (constant flux) conduit. At the top of the pipe, a range of boundary conditions that are relevant at a volcanic vent were imposed, going from open to plugged vent. The results obtained illustrate that a change in boundary conditions in the conduit concur to affect the dynamic of slug expansion and burst: an upward flux at the base of the conduit attenuates the magnitude of the pressure transients, while a rheological stiffening in the top-most region of conduit changes dramatically the magnitude of the observed pressure transients, favoring a sudden, and more energetic pressure release into the overlying atmosphere. Finally, a discussion on the implication of changing boundary on the oscillatory processes generated at the volcanic scale is also given.

C 3-symmetric discotic liquid crystalline materials for molecular electronics: versatile synthesis and self-organization

This thesis presents the versatile synthesis and self-organization of C3-symmetric discotic nanographene molecules as well as their potential applications as materials in molecular electronics. The details can be described as follows: 1) A novel synthetic strategy towards properly designed C3 symmetric 1,3,5-tris-2’arylbenzene precursors has been developed. After the final planarization by treatment with FeCl3 under mild conditions, for the first time, it became possible to access a variety of new C3-symmetric hexa-peri-hexabenzocoronenes (HBCs) and a series of triangle-shaped nanographenes. D3 symmetric HBC with three alkyl substituents and C2 symmetric HBC with two alkyl substituents were synthesized and found to show the surprising decrease of isotropic points., the self-assembly at the liquid-solid interface displayed a unique zigzag and flower patterns. 2) Triangle-shaped discotics revealed a unique self-assembly behavior in solution, solid state as well as at the solution-substrate interface. A mesophase stability over the broad temperature range with helical supramoelcular arrangement were observed in the bulk state. The honeycomb pattern as the result of novel self-assembly was presented. Triangle-shaped discotics with swallow alkyl tails were fabricated into photovoltaic devices, the supramolecular arrangement upon thermal treatment was found to play a key role in the improvement of solar efficiency. 3) A novel class of C3 symmetric HBCs with alternating polar/apolar substituents was synthesized. Their peculiar self-assembly in solution, in the bulk and on the surface were investigated by NMR techniques, X-ray diffraction as well as different electron microscope techniques. 4) A novel concept for manipulating the intracolumnar stacking of discotics and thus for controlling the helical pitch was presented. A unique staggered stacking in the column was achieved for the first time. Theoretical simulations confirmed this self-organization and predicted that this packing should show the highest charge carrier mobility for all discotics.

Liquid crystalline phases of anisotropic, polymer functionalized nanoparticles

Diese Arbeit beschäftigt sich mit der Polymerfunktionalisierung formanisotroperrnNanopartikel wie TiO2 Nanostäbchen oder Kohlenstoff Nanoröhren. Dies dient derrnSolubilisierung und sterischen Stabilisierung in organischen Medien, da diesernionenfrei hergestellt werden können, was eine Nutzung für nanoskopische,rnelektrische Schaltkreise ermöglicht. Die Polymere wurden mittels der RAFTrn(reversible addition-fragmentation chain transfer) Polymerisation mit engenrnMolekulargewichtsverteilungen hergestellt. Im Detail wurden Ankergruppen inrnBlockcopolymere und an der Alphaposition eingeführt, welche eine Anbindung an diernNanopartikeloberfläche ermöglichen. Die Polymere wurden durch Variation derrnverschiedenen Blocklängen für eine bestmögliche Adsorption optimiert. Die sorngewonnenen Polymer funktionalisierten Nanopartikel zeigten eine gute Löslichkeit inrnorganischen Medien und zeigten zudem eine lyotropes, flüssigkristallinesrnPhasenverhalten. Dies war aufgrund der Formanisotropie zu erwarten, zeigte jedochrnebenfalls ein unerwartetes thermotropes Verhalten, welches durch die Polymerhüllernerzeugt wurde. Die Flüssigkristalle wurden eingehend mittels polarisierterrnMikroskopie und Differential Scanning Calorimetry (DSC) untersucht. Diernflüssigkristallinen Phasen aus Nanostäbchen und –röhren wurde dann zurrnOrientierung der anisotropen Nanopartikel benutzt und es konnten makroskopischrngeordnete Proben hergestellt werden. Die Polymerhülle um die Nanopartikelrnermöglichte es ebenfalls diese in Polymerfilme einzuarbeiten und sornNanopartikelverstärkte Kunststoffe herzustellen.

Modeling and simulations of nanoparticles in liquid crystalline systems

The aim of this work is to investigate, using extensive Monte Carlo computer simulations, composite materials consisting of liquid crystals doped with nanoparticles. These systems are currently of great interest as they offer the possibility of tuning the properties of liquid crystals used in displays and other devices as well as providing a way of obtaining regularly organized systems of nanoparticles exploiting the molecular organization of the liquid crystal medium. Surprisingly enough, there is however a lack of fundamental knowledge on the properties and phase behavior of these hybrid materials, making the route to their application an essentially empirical one. Here we wish to contribute to the much needed rationalization of these systems studying some basic effects induced by different nanoparticles on a liquid crystal host. We investigate in particular the effects of nanoparticle shape, size and polarity as well as of their affinity to the liquid crystal solvent on the stability of the system, monitoring phase transitions, order and molecular organizations. To do this we have proposed a coarse grained approach where nanoparticles are modelled as a suitably shaped (spherical, rod and disk like) collection of spherical Lennard-Jones beads, while the mesogens are represented with Gay-Berne particles. We find that the addition of apolar nanoparticles of different shape typically lowers the nematic–isotropic transition of a non-polar nematic, with the destabilization being greater for spherical nanoparticles. For polar mesogens we have studied the effect of solvent affinity of the nanoparticles showing that aggregation takes places for low solvation values. Interestingly, if the nanoparticles are polar the aggregates contribute to stabilizing the system, compensating the shape effect. We thus find the overall effects on stability to be a delicate balance of often contrasting contributions pointing to the relevance of simulations studies for understanding these complex systems.

Liquid crystalline elastomers as stimuli-responsive microactuators

Liquid crystalline elastomers (LCEs) are known to perform a reversible change of shape upon the phase transition from the semi-ordered liquid crystalline state to the chaotic isotropic state. This unique behavior of these “artificial muscles” arises from the self-organizing properties of liquid crystals (mesogens) in combination with the entropy-elasticity of the slightly crosslinked elastomer network. In this work, micrometer-sized LCE actuators are fabricated in a microfluidic setup. The microtubular shear flow provides for a uniform orientation of the mesogens during the crosslinking, a perquisite for obtaining actuating LCE samples. The scope of this work was to design different actuator geometries and to broaden the applicability of the microfluidic device for different types of liquid crystalline mesogens, ranging from side-chain to main-chain systems, as well as monomer and polymer precursors. For example, the thiol-ene “click” mechanism was used for the polymerization and crosslinking of main-chain LCE actuators. The main focus was, however, placed on acrylate monomers and polymers with LC side chains. A LC polymer precursor, comprising mesogenic and crosslinkable side-chains was synthesized. Used in combination with an LC monomer, the polymeric crosslinker promoted a stable LC phase, which allowed the mixture to be isothermally handled in the microfluidic reactor. If processed without the additional LC components, the polymer precursor yielded actuating fibers. A suitable co-flowing continuous phase facilitates the formation of a liquid jet and lowers the tendency for drop formation. By modification of the microfluidic device, it was further possible to prepare core-shell particles, comprised of an LCE shell and filled with an isotropic liquid. In analogy to the heart, a hollow muscle, the elastomer shell expels the inner liquid core upon its contraction. The feasibility of the core-shell particles as micropumps was demonstrated. In general, the synthesized LCE microactuators may be utilized as active components in micromechanical and lab-on-chip systems.

Liquid crystalline cellulose derivatives for mirrorless lasing

In this thesis cholesteric films made of liquid crystalline cellulose derivatives with improved optical properties were prepared. The choice of the solvent, hydrogen bond influencing additives, the synthetic realization of a very high degree of substitution on the cellulosic polymer and the use of mechanical stirring at the upper concentration limit of the liquid crystalline range were the basis for an improved alignment of the applied cellulose tricarbamates. In combination with a tuned substrate treatment and film preparation method, cholesteric films were obtained, with optical properties that were theoretically predicted and only known from low molecular weight liquid crystals so far. Subsequent polymerization allowed a permanent fixing of the alignment and the fabrication of free standing and insensitive films.rnThe incorporation of inorganic nanorods into the cholesteric host material was mediated with tailored block copolymers, available via controlled radical polymerization methods. In addition to the shape match between the rodlike mesogens of the host and the nanorods it was possible to increase the miscibility of both materials. Nevertheless, the size of the nanorods, in comparison to the mesogens, in these densely packed liquid crystalline phases as well as their long equilibration times were the reasons for phase separation. Nanorods are, in principle, valuable substitutes for organics, but their utilization in cellulosic CLC was not to be combined with a high quality alignment of the cholesteric structure.rnA swelling process of polymerized films in a dye solution or dissolving dyes in non-polymerized CLC was used for incorporation of the organic chromophores. With the first method the CLC could be aligned and polymerized without any disturbance due to dye molecules. The optical properties of dye and CLC were matched, with regard to mirrorless lasing devices. The dye was optically excited and laser emission supported by the cholesteric cavity was obtained. The polarization and wavelength of the emitted radiation as well as its bandwidth, the obtained interference pattern and threshold behavior of the emission proofed the feedback mechanism that was not believed to be realizable in liquid crystalline polymers. rnUtilization of a microfluidic co-flow injection device enabled us to transfer the properties of cellulosic CLC from the planar film shape to spherical micrometer sized particles. The pure material yielded particles with distorted mesogen alignment similar to films prepared by capillary flow. Dilution of the CLC with a solvent that migrated into the carrier phase during particle preparation provided the basis for particles with well ordered areas. rnAlthough cellulose derivatives were known for their liquid crystalline behavior for decades and synthesized in mass production, their application as feedback material was affected by bad optical properties. In comparison to low molar mass compounds, the low degree of order in the CLC phase was the cause. With the improved material, defined lasing emission was shown and characterized. Derivatives of cellulose are desirable materials, because, as a renewable resource, they are available in large amounts for a low price and need only simple derivatization reactions. The fabrication of CLC films with tunable lasing emission, for which this thesis can provide a starting point, is in good agreement with today's requirements of modern technology and its miniaturization.rn

Testing the TICT State Hypothesis: an Investigation into the Solvatochromic Behavior of 2-Naphthalenylmethylene Malononitrile

Towards the goal of investigating the possible Twisted Intramolecular Charge Transfer (TICT) state mechanism of fluorescence emission, two aromatic dicyanovinyl compounds, 2-(naphthalene-2-ylmethylene) malononitrile (DCN) and a rigidified analogue, 3,4-dihydrophenanthren-1(2H)-ylidene)malononitrile (RDCN) were synthesized and their absorption and steady-state fluorescence emission spectra characterized. The spectral characterization was divided into two studies: first, DCN and RDCN were characterized in liquid solvents of increasing polarity; second, DCN and RDCN were characterized in viscous solvents and rigid glass media. The absorption spectra for both DCN and RDCN in all solvents demonstrated little to no solvatochromism. Emission results for DCN and RDCN in liquid solvents of increasing polarity showed DCN possessing strong solvatochromism while RDCN showed much less solvatochromism. Using the Lippert-Mataga equation, the difference between the ground and excited state dipole moment for DCN was estimated to be 8.4 + 0.4 Debye and between ~3.0 to 5.0 Debye for RDCN. Quantum yield measurements for DCN and RDCN in hexane, diethyl ether and acetonitrile were less than 0.01 and independent of polarity for both both solvents, with DCN generally possessing a quantum yield 3-4 times greater than RDCN. Experiments in glass media for DCN and RDCN showed a lessening of their solvatochromic character in both polar and non-polar glasses. These data provide strong evidence for a link between molecular flexibility and solvatochromism. However, while these data are consistent with a TICT state hypothesis for the emission mechanism, an alternative mechanism proposed by Maroncelli et al.10 involving rotation about the dicyanovinyl double bond in the excited state remains a possibility as well.

Revision of a Liquid Fuel Airblast Atomizer and Installation of a Laser Extinction System for Measurement of Soot Produced During Liquid Fuel Combustion

Studying liquid fuel combustion is necessary to better design combustion systems. Through more efficient combustors and alternative fuels, it is possible to reduce greenhouse gases and harmful emissions. In particular, coal-derived and Fischer-Tropsch liquid fuels are of interest because, in addition to producing fewer emissions, they have the potential to drastically reduce the United States' dependence on foreign oil. Major academic research institutions like the Pennsylvania State University perform cutting-edge research in many areas of combustion. The Combustion Research Laboratory (CRL) at Bucknell University is striving to develop the necessary equipment to be capable of both independent and collaborative research efforts with Penn State and in the process, advance the CRL to the forefront of combustion studies. The focus of this thesis is to advance the capabilities of the Combustion Research Lab at Bucknell. Specifically, this was accomplished through a revision to a previously designed liquid fuel injector, and through the design and installation of a laser extinction system for the measurement of soot produced during combustion. The previous liquid fuel injector with a 0.005" hole did not behave as expected. Through spray testing the 0.005" injector with water, it was determined that experimental errors were made in the original pressure testing of the injector. Using data from the spray testing experiment, new theoretical hole sizes of the injector were calculated. New injectors with 0.007" and 0.0085" orifices were fabricated and subsequently tested to qualitatively validate their behavior. The injectors were installed in the combustion rig in the CRL and hot-fire tested with liquid heptane. The 0.0085" injector yielded a manageable fuel pressure and produced a broad flame. A laser extinction system was designed and installed in the CRL. This involved the fabrication of a number of custom-designed parts and the specification of laser extinction equipment for purchase. A standard operating procedure for the laser extinction system was developed to provide a consistent, safe method for measuring soot formation during combustion.

DEVELOPMENT OF CONFOCAL IMAGING TECHNIQUES FOR PROBING INTERFACIAL DYNAMICS IN MICROSCALE, GAS-LIQUID, TWO-PHASE FLOW

Micro-scale, two-phase flow is found in a variety of devices such as Lab-on-a-chip, bio-chips, micro-heat exchangers, and fuel cells. Knowledge of the fluid behavior near the dynamic gas-liquid interface is required for developing accurate predictive models. Light is distorted near a curved gas-liquid interface preventing accurate measurement of interfacial shape and internal liquid velocities. This research focused on the development of experimental methods designed to isolate and probe dynamic liquid films and measure velocity fields near a moving gas-liquid interface. A high-speed, reflectance, swept-field confocal (RSFC) imaging system was developed for imaging near curved surfaces. Experimental studies of dynamic gas-liquid interface of micro-scale, two-phase flow were conducted in three phases. Dynamic liquid film thicknesses of segmented, two-phase flow were measured using the RSFC and compared to a classic film thickness deposition model. Flow fields near a steadily moving meniscus were measured using RSFC and particle tracking velocimetry. The RSFC provided high speed imaging near the menisci without distortion caused the gas-liquid interface. Finally, interfacial morphology for internal two-phase flow and droplet evaporation were measured using interferograms produced by the RSFC imaging technique. Each technique can be used independently or simultaneously when.

Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants

Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of approximately 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 +/- 1.5 contractions/min, 22 +/- 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was reversed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal positive pressure of 2.33 +/- 0.77 cm H(2)O was recorded in rabbit fetal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the airway wall and adjacent parenchyma. The expansion of the compliant endbuds by the fluid shifts at the airway tip may promote their growth into the surrounding mesenchyme.

Spectroscopy and detectability of liquid brines on mars

Recent geomorphological observations as well as chemical and thermodynamic studies demonstrate that liquid water should be stable today on the Martian surface at some times of the day. In Martian conditions, brines would be particularly more stable than pure water because salts can depress the freezing point and lower the evaporation rate of water. Despite this evidence, no clear spectral signature of liquid has been observed so far by the hyperspectral imaging spectrometers OMEGA and CRISM. However, past spectral analysis lacks a good characterization of brines׳ spectral signatures. This study thus aims to determine how liquid brines can be detected on Mars by spectroscopy. In this way, laboratory experiments were performed for reproducing hydration and dehydration cycles of various brines while measuring their spectral signatures. The resulting spectra first reveal a very similar spectral evolution for the various brine types and pure water, with the main difference observed at the end of the dehydration with the crystallization of various hydrated minerals from brines. The main characteristic of this spectral behavior is an important decoupling between the evolution of albedo and hydration bands depths. During most of the wetting/drying processes, spectra usually display a low albedo associated with shallow water absorption band depths. Strong water absorption band depth and high albedo are respectively only observed when the surface is very wet and when the surface is very dry. These experiments can thus explain why the currently active Martian features attributed to the action of a liquid are only associated with low albedo and very weak spectral signatures. Hydration experiments also reveal that deliquescence occurs easily even at low temperature and moderate soil water vapor pressure and could thus cause seasonal darkening on Mars. These experiments demonstrate that the absence of water absorptions in CRISM in the middle afternoon does not rule out water activity and suggest future spectral investigations to identify water on the Martian surface.

A steerable UV laser system for the calibration of liquid argon time projection chambers

A number of liquid argon time projection chambers (LAr TPCs) are being built or are proposed for neutrino experiments on long- and short baseline beams. For these detectors, a distortion in the drift field due to geometrical or physics reasons can affect the reconstruction of the events. Depending on the TPC geometry and electric drift field intensity, this distortion could be of the same magnitude as the drift field itself. Recently, we presented a method to calibrate the drift field and correct for these possible distortions. While straight cosmic ray muon tracks could be used for calibration, multiple coulomb scattering and momentum uncertainties allow only a limited resolution. A UV laser instead can create straight ionization tracks in liquid argon, and allows one to map the drift field along different paths in the TPC inner volume. Here we present a UV laser feed-through design with a steerable UV mirror immersed in liquid argon that can point the laser beam at many locations through the TPC. The straight ionization paths are sensitive to drift field distortions, a fit of these distortion to the linear optical path allows to extract the drift field, by using these laser tracks along the whole TPC volume one can obtain a 3D drift field map. The UV laser feed-through assembly is a prototype of the system that will be used for the MicroBooNE experiment at the Fermi National Accelerator Laboratory (FNAL).