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Dipolar molecules have been grafted on the surface of indium-tin-oxide plates. Using these modified substrates as anodes for organic diodes made from poly-vinylcarbazole enhances the hole current by 1-2 orders of magnitude as compared to diodes with nonmodified anodes. The organization and surface concentration of the grafted monolayer, determined by infrared spectroscopy, show that the grafted layer is not densely packed. The influence of the dipolar molecules on the energy barrier height for the injection of hole current into the organic layer is also measured by internal photoemission, evidencing that the barrier is lowered by the molecular grafting. The free space around the grafted molecules allows for their reorientation under electric field. The energy barrier height has been measured as a function of time during this reorientation. [ABSTRACT FROM AUTHOR]

Internal photoemission has been used to determine the energy barriers for electrode/organic-layer interfaces in organic light-emitting diodes. The diodes were polymer or small-molecule single-layer structures made from poly-(9-vinylcarbazole), poly-(9,9-dihexylfluorene), tris-(8-hydroxyquinolinate) aluminum, and N,N[sup ′]- Bis(3-methylphenyl)-N,N[sup ′]-diphenylbenzidine with indium tin oxide or metallic electrodes (Al, Au, or Cu). The internal photoemission yield follows the Fowler theory and the energy barriers exhibit a small lowering for increasing internal electric field due to image-force potential. There is an offset of 0.4-0.5 eV between the actual energy barriers and the naive expectations from the difference between the energy levels taken from the literature. Interface dipole effects and uncertainties concerning the electrochemical determination of the highest occupied molecular orbital levels are the most plausible origins of this difference. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We assessed the effects of seasonal variations (dry and wet), substrate type (litter and soil), and land use (grazing) on the relationship between cellulolysis and humification processes in the west-central arid region of Argentina to establish a powerful and realistic pattern to close this information gap in terrestrial C modeling in dry lands. Three composite samples of soil and litter were collected from ungrazed and grazed sites, and the following parameters were analyzed: (i) in all samples: water content, cellulolytic microorganism abundance, activity, and efficiency (activity/abundance); (ii) in litter: organic C, insoluble fiber, and phenol contents; and (iii) in soil: organic C, fulvic and humic acids, nonhumic substances, and polymerization and humification indexes. The cellulolysis and humification processes were significantly affected by seasonal variations, substrate type, and grazing. Many significant interactions were detected among the analyzed factors, with cellulolytic activity the most sensitive parameter. All of the cellulolysis parameters were correlated with the total soil organic C and humified fractions, although there was no significant correlation with nonhumic substances. Our results suggest that cellulolytic activity and efficiency are two key parameters that should be taken into account in modeling decomposition and transformation of organic matter in soil. This approach should contribute to filling the existing gap of knowledge found in the existing literature about microbial activity, substrate, and products related to terrestrial C modeling. [ABSTRACT FROM AUTHOR]

Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background) are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that fibrillin-2 can sequester BMP complexes in a latent state. [ABSTRACT FROM AUTHOR]

Mp is an irradiation-induced mouse mutation associated with microphthalmia, micropinna and hind limb syndactyly. We show that Mp is caused by a 660 kb balanced inversion on chromosome 18 producing reciprocal 3-prime gene fusion events involving Fbn2 and Isoc1. The Isoc1-Fbn2 fusion gene (Isoc1Mp) mRNA has a frameshift and early stop codon resulting in nonsense mediated decay. Homozygous deletions of Isoc1 do not support a significant developmental role for this gene. The Fbn2-Isoc1 fusion gene (Fbn2Mp) predicted protein consists of the N-terminal Fibrillin-2 (amino acids 1–2646, exons 1–62) lacking the C-terminal furin-cleavage site with a short out-of-frame extension encoded by the final exon of Isoc1. The Mp limb phenotype is consistent with that reported in Fbn2 null embryos. However, severe eye malformations, a defining feature of Mp, are not seen in Fbn2 null animals. Fibrillin-2Mp forms large fibrillar structures within the rough endoplasmic reticulum (rER) associated with an unfolded protein response and quantitative mass spectrometry shows a generalised defect in protein secretion in conditioned media from mutant cells. In the embryonic eye Fbn2 is expressed within the peripheral ciliary margin (CM). Mp embryos show reduced canonical Wnt-signalling in the CM – known to be essential for ciliary body development - and show subsequent aplasia of CM-derived structures. We propose that the Mp “worse-than-null” eye phenotype plausibly results from a failure in normal trafficking of proteins that are co-expressed with Fbn2 within the CM. The prediction of similar trans-acting protein effects will be an important challenge in the medical interpretation of human mutations from whole exome sequencing. [ABSTRACT FROM AUTHOR]

The Belén flora, in north coastal Peru, is the most diverse fruit and seed assemblage yet known from the Paleogene of South America. Little original paleobotanical work has been performed on this assemblage since the pioneering treatments published by E. W. Berry in the 1920s, and the precise age has not been determined. Nevertheless, the flora has been regarded as a focal point in understanding the vegetational, orogenic, and climatic history of northern South America, and in recent literature it has been assumed to be early Eocene. In order to tighten this age assignment, which has varied from early Eocene to early Oligocene in the opinions of different authors, we revisited the Belén site, measured the stratigraphic section, and processed the fruit- and seed-containing sediment for age-diagnostic microfossils. Although pollen and foraminifera were not recovered, the sediment is rich in diatoms. The diatom assemblage includes Lisitzinia ornata and Rocella vigilans, among others, indicating a latest early Oligocene age (∼30-28.5 Ma) for these deeper marine sediments, which we infer to have been subsequently reworked into the Belén environment. We also reevaluate the botanical identifications, which are based on the original museum specimens supplemented by more recently collected specimens. The Belén flora provides a window into extinct forests in South America that were present before the rising of the Andes in western Peru. [ABSTRACT FROM AUTHOR]

Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes. A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated, even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently appreciated. Mutations in FBN1 are mainly responsible for the Marfan syndrome (MFS), recognized by its pleiotropic clinical features including tall stature and arachnodactyly, aortic dilatation and dissection, and ectopia lentis. Each of the many different mutations in FBN1 known to cause MFS must lead to similar clinical features through common mechanisms, proceeding principally through the activation of TGFb signaling. Here we show that a novel FBN1 mutation in a family with Weill-Marchesani syndrome (WMS) causes thick skin, short stature, and brachydactyly when replicated in mice. WMS mice confirm that this mutation does not cause MFS. The mutation deletes three domains in fibrillin-1, abolishing a binding site utilized by ADAMTSLIKE-2, -3, -6, and papilin. Our results place these ADAMTSLIKE proteins in a molecular pathway involving fibrillin-1 and ADAMTS-10. Investigations of microfibril ultrastructure in WMS humans and mice demonstrate that modulation of the fibrillin microfibril scaffold can influence local tissue microenvironments and link fibrillin-1 function to skin homeostasis and the regulation of dermal collagen production. Hence, pathogenetic mechanisms caused by dysregulated WMS microenvironments diverge from Marfan pathogenetic mechanisms, which lead to broad activation of TGFb signaling in multiple tissues. We conclude that local tissue-specific microenvironments, affected in WMS, are maintained by a fibrillin-1 microfibril scaffold, modulated by ADAMTSLIKE proteins in concert with ADAMTS enzymes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Assess changes in resource utilization, work and activity impairment, and health utility among OAB patients continuing to have urgency symptoms with tolterodine ER 4 mg and willing to try solifenacin 5/10 mg. RESEARCH DESIGN AND METHODS: This was an open-label, non-comparative, flexible-dosing, multicenter, 12-week study assessing the efficacy and safety of solifenacin 5/10 mg/day. Patients receiving tolterodine ER 4 mg/day for >/=4 weeks but continuing to experience residual urgency symptoms (>/=3 urgency episodes/24 h) were enrolled into the study. After a 14-day washout, patients began treatment with solifenacin 5 mg/day with dosing adjustments allowed at Weeks 4 and 8. MAIN OUTCOME MEASURES: Outcomes were assessed using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP), Health Utilities Index (HUI), and a resource utilization questionnaire administered at Pre-Washout and Week 12. RESULTS: Patients (n=440) reported significantly fewer physician office visits (p<0.0001), UTIs (p<0.0001), and pads/diapers (p=0.0009) during the study period while receiving solifenacin 5/10 mg/day, compared with the Pre-Washout period when receiving tolterodine ER 4 mg/day. After 12 weeks of treatment with solifenacin 5/10 mg/day, patients reported a reduction in work time missed (p=0.0017), less impairment while working (p<0.0001), less overall work impairment (p<0.0001) and a reduction in activity impairment (p<0.0001) compared to Pre-Washout. There was no significant difference in health utility scores. Treatment-emergent adverse events were mostly anticholinergic in nature, and were mild to moderate in severity. CONCLUSION: Overall, solifenacin 5/10 mg/day improved work productivity, activity participation, and reduced medical care use in OAB patients who continued to have urgency symptoms with tolterodine ER 4 mg/day and wished to switch to solifenacin 5/10 mg. This was an open-label, non-comparative study; therefore, further research is needed to confirm these results. [ABSTRACT FROM AUTHOR]

We study a method of seed-based lossless filtration for approximate string matching and related bioinformatics applications. The method is based on a simultaneous use of several spaced seeds rather than a single seed as studied by Burkhardt and Karkkainen. We present algorithms to compute several important parameters of seed families, study their combinatorial properties, and describe several techniques to construct efficient families. We also report a large-scale application of the proposed technique to the problem of oligonucleotide selection for an EST sequence database. [ABSTRACT FROM PUBLISHER]

In this paper we take a closer look at the decay phase of a passive, diffusing, scalar field undergoing steady, three-dimensional chaotic advection. The energy spectrum of the scalar is obtained by numerical simulation of the advection–diffusion equation at high Pe´clet number. At large times, the spectral decay is found to be exponential and self-similar. It is emphasized that the asymptotic decay-time is an important measure of mixing efficiency, alongside the time required for diffusion to first become effective. The large-wavenumber spectral form, representing the distribution of scalar energy over small scales, is analyzed. Power-law behavior is found at scales intermediate between the large ones, comparable in size with the entire flow volume, and the smallest ones, at which diffusion is effective and the spectrum falls off exponentially with increasing wavenumber. Fitting of the numerical results allows the exponent of the power-law to be estimated. It is observed to vary with the parameters of the flow, taking negative values which can be either less than or greater than -1. This implies that the dominant spectral energy at high P may be either at small, large or intermediate scales, depending on the flow. In consequence, the qualitative nature of the scalar field during the decay phase varies from flow to flow, resulting in differing behavior of the predicted decay times in the large P limit obtained by asymptotic analysis. The case in which the spectral exponent exceeds -1 is shown to produce more rapid mixing and the corresponding asymptotic expression for the decay time, independent of P and involving two spectral parameters, is suggested as a quantitative means for optimizing the flow. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Osteoblast adhesion on materials will depend on the surface aspects of materials which may be described according to their surface chemistry, surface topography or surface energy. To separate the effects of roughness and composition of materials on osteoblast response, we chose to compare substrates with various surface composition but with the same smooth surface. Ti6Al4V alloy, stainless steel, glass and standard tissue culture polystyrene were tested. Adhesion was evaluated using specific antibodies against adhesion proteins and by a quantitative cell detachment assay. After 1, 7 and 14 days, cells expressed extracellularly fibronectin fibers, and intracellularly type I collagen and osteopontin. Vinculin-labeled focal contacts were visible on all materials but were more frequent on glass and stainless steel surfaces. β1-integrin subunit-labeled patches were visible on all surfaces at each delay. The quantitative cell detachment assay showed few differences between materials. Adhesion was higher on metallic substrates although cell proliferation was higher on glass and stainless steel compared to tissue culture polystyrene and Ti6Al4V alloy. Substrates with various surface composition but with the same surface topography did not induce significant differences of adhesion although cell proliferation was variable. [ABSTRACT FROM AUTHOR]

A direct wafer bonding process has been developed to accurately control both the bonding interface twist and tilt angles between a monocrystalline layer and a bare monocrystalline wafer. This process is based on the bonding of twin surfaces produced by splitting a single wafer, using for instance the Smart Cut® process. A targeted control of ±0.005° is obtained for the twist angle without any crystallographic measurement. Moreover, pure twist-bonded interfaces have been artificially made between two (001) bonded silicon surfaces. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The mathematical formalism of generating functionals was adopted for the unified statistical description of a typical experiment in fluorescence fluctuation spectroscopy. The generating functionals formalism leads to a set of functional equations, linking the statistical characteristics of the excitation and detected photons via the characteristics of a molecular system. The statistical characteristics of the detected photons can then be obtained in a straightforward and consistent way. We particularly show how characteristics such as the photocount correlation function and the probability distribution of the number of photocounts per detection interval can be derived based on the developed theory. We further demonstrate that the probability density distribution of the first and single photocount time occurrences in the detection interval also can be used for probing molecular behavior. The presented approach is applicable to a broad range of experimental configurations (continuous and pulsed excitation, one-photon and two-photon laser excitation, scanning laser excitation) and molecular movements (diffusion in two and three dimensions, fluid flows). © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The modeling of excited-state processes in photophysics can conveniently be done within the framework of compartmental analysis. In compartmental analysis substantial attention has been devoted to the study of deterministic identifiability, which verifies whether it is possible to determine the parameters of the compartmental model from error-free data. In this paper the similarity transformation approach is applied to the identifiability problem of the photophysical model for reversible intermolecular two-state excited-state processes. This method provides straightforward relations between the true and alternative sets of the system parameters. This allows one to explore directly the parameter space for identifiability. Since absolute values for the spectral parameters associated with excitation and emission are not available from time-resolved fluorescence experiments, the original similarity transformation approach to the identifiability problem was reformulated in terms of normalized spectral parameters, which are experimentally accessible. It is shown that six decay traces--measured at two coreactant concentrations and three emission wavelengths--are required for the model to be locally identifiable. Two sets of rate constants and associated spectral parameters may be found under these conditions. Enclosure in the analysis of the monoexponential decay at very low coreactant concentration results in global identifiability. The non-negativity requirement of the spectral parameters also can lead to the unique solution. If the fluorescence decays are independent of the emission wavelength, additional information about the photophysical system is necessary for identifiability. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A model for diffusion-mediated intramolecular fluorescence quenching based on the analytical solution of the Smoluchowski differential equation is considered. It is assumed that quenching occurs with a finite intrinsic rate at the distance of closest contact between the reactants. The solution has been worked out in terms of Laplace transforms with the aim to perform a deterministic identifiability study of this model. It is shown that the rate constant of excited-state deactivation and the system dimensionality can be uniquely recovered without additional information from a single fluorescence decay trace. The other system parameters (the diffusion coefficient, the intrinsic reaction rate constant, the distance of closest approach, and the distance of maximal separation), influencing the diffusion-controlled quenching, can be determined up to a scaling factor. However, if a priori information about one of these parameters is available, the model becomes globally identifiable (i.e., all model parameters can be uniquely determined). © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

InGaAsP/InP quantum well (QW) ridge waveguide lasers emitting nominally at 1310 nm have been ‘‘blue-shifted’’ selectively (as much as 70 nm) on a full 50-mm-diameter wafer after growth. P+ ion implantation at 1 MeV, 200 °C through a variable thickness SiO2 mask was used to induce various degrees of QW intermixing after postimplantation annealing at 700 °C. Irrespective of the amount of intermixing induced (blue shift), all fabricated devices exhibited 20–25 mA lasing threshold current and 0.25–0.30 W/A differential quantum efficiency. Device reliability was equivalent to standard (nonimplanted) lasers when the wavelength shift was 35 nm or less, corresponding to predicted lifetime in excess of 25 years while operating cw at 25 °C. The performance and reliability data clearly indicate that the concentration of residual defects introduced in the active region by the implantation/annealing process is negligibly small. The present results, which are a product of a straightforward fabrication process, suggest the possibility of manufacturing high-reliability, low-cost, monolithically integrated optoelectronic chips containing, for example, selectively tuned lasers, optical amplifiers, modulators, and waveguides. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Rapid thermal processing for junction formation is emerging as a low cost technique for solar cell as well as for other semiconductor device production. Compared to conventional furnace processing, process differences are not only in very high heating and cooling rates, but also in the incoherent emitted radiation spectrum, which can act on dopant diffusion. The photons emitted from tungsten halogen lamps go from far ultraviolet, over visible to infrared light. In this work additional mercury ultraviolet lamps are used during rapid thermal annealing to analyze the influence of high energetic photons on diffusion mechanisms. The diffusion results are discussed in terms of radiation spectrum, involving analysis of diffusion profiles and sheet resistances. © 1998 American Institute of Physics. [ABSTRACT FROM AUTHOR]