Partial hydrodynamic screening of confined linear and circular double-stranded DNA dynamics.

We performed experiments and simulations to investigate the influence of hydrodynamic interaction on the diffusion dynamics of circular and linear λ-DNA confined in nanoslits. Contrary to the common assumption that intrachain hydrodynamic interaction (HI) is completely screened when polymers are confined in channels with height h smaller than the radius of gyration R(g), it is found that the HI is partially screened and approaches complete screening only for R(g)≪h. For λ-DNA, the HI becomes nearly completely screened only when the channel height is smaller than the Kuhn length. In addition, the dynamics of linear and circular λ-DNA in very strong confinement is shown to be independent of the chain topology.

Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

Predictors of early clinical deterioration after acute ischemic stroke.

The measurements for predicting early deterioration of stroke patients is controversial. We studied laboratory measurements and previously identified risk factors to identify factors or predictors of early deterioration after stroke. A prospective observational study of 196 patients with first-time acute ischemic stroke was performed. Demographic data, patient histories, laboratory measurements, and initial stroke severity assessments were recorded. Patients with early deterioration in National Institutes of Health Stroke Scale scores (increase ≥3 points within 3 days) were defined as having stroke-in-evolution (SIE). Thirty patients were diagnosed with SIE. An initial National Institutes of Health Stroke Scale score of 12 or higher, a Glasgow Coma Scale score of 12 or lower, d-dimers more than 1000, or blood urea nitrogen/creatinine (BUN/Cr) ratio higher than 15 were more frequent in SIE patients. After multivariate analysis, only a BUN/Cr higher than 15 was independent predictor of SIE. These patients were 3.41-fold more likely to have SIE (P = .008). These findings suggest that BUN/Cr may be a novel predictor of SIE, potentially useful in emergency departments.

White-light emission from an upconverted emission with an organic triplet sensitizer.

An energy upconversion system based on triplet-triplet annihilation exploiting an organic triplet sensitizer is devised and has achieved a white-light emission with a low power laser excitation.

Real-time data acquisition incorporating high-speed software correlator for single-molecule spectroscopy.

Single-molecule spectroscopy and detection are powerful techniques for the study of single fluorescent particles and their interaction with their environment. We present a low-cost system for simultaneous real-time acquisition, storage of inter-photon arrival times and the calculation and display of the fluorescence time trace, autocorrelation function and distribution of delays histogram for single-molecule experiments. From a hardware perspective, in addition to a multi-core computer, only a standard low-cost counting board is required as processing is software-based. Software is written in a parallel programming environment with time crucial operations coded in ANSI-C. Crucial to system performance is a simple and efficient real-time autocorrelation algorithm (acf) optimized for the count rates (approximately 10(4) cps) encountered in single-molecule experiments. The algorithm's time complexity is independent of temporal resolution, which is maintained at all time delays. The system and algorithm's performance was validated by duplicating the signal from the photon detector and sending it to both the ordinary counter board and a commercial correlator simultaneously. The data acquisition system's robustness under typical single-molecule experimental conditions was tested by observing the diffusion of Rhodamine 6G molecules in deionized water.

Excited-state backbone twisting of polyfluorene as detected from photothermal after-effects.

By means of time-resolved photoluminescence and photothermal techniques, after-effects from excited-state dynamics, energy migration, and conformational rearrangement of poly(9,9-di-n-octyl-2,7-fluorene) (PFO) and its homologues has been examined and interpreted with rotational potential maps from quantum mechanical calculations. Steady-state photoluminescence spectral changes and time-resolved photoluminescence measurements of oligofluorenes and PFO diluted in toluene suggest excited state ring torsion occurring within 30 ps of photoexitation. With all effects from internal conversion/intersystem crossing processes properly accounted for, we show that the conformational changes associated with this twisting motion can be quantitatively probed by means of photothermal methods. Results suggest mean torsion between neighboring fluorene units by ca. 40 degrees upon excitation, in agreement with the shift of rotational potential minimum from +/-40 degrees (and +/-140 degrees) in the ground state to +/-20 degrees (and +/-160 degrees) in the first excited singlet state according to results of quantum mechanical calculations.

Static conformation and dynamics of single DNA molecules confined in nanoslits.

Nearly thirty years ago, Daoud and de Gennes derived the scaling predictions for the linear polymer chains trapped in a slit with dimension close to the Kuhn length; however, these predictions have yet to be compared with experiments. We have fabricated nanoslits with vertical dimension similar to the Kuhn length of ds-DNA (110nm) using standard photolithography techniques. Fluorescently labeled single DNA molecules with contour lengths L ranging from 4 to 75 microm were successfully injected into the slits and the chain molecules undergoing Brownian motions were imaged by fluorescence microscopy. The distributions of the chain radius of gyration and the two-dimensional asphericity were measured. It is found that the DNA molecules exhibit highly anisotropic shape and the mean asphericity is chain length independence. The shape anisotropy of DNA in our measurements is between two and three dimensions (2D and 3D). The static scaling law of the chain extension and the radius of gyration , approximately L(nu) were observed with nuR(parallel)=0.65+/-0.02 and nu(Rg)=0.68+/-0.05. These results are close to the average value between two (nuR parallel,Rg=0.75) and three (nuR parallel,Rg=0.6) -dimensional theoretical value. The scaling of the extensional and rotational relaxation time are between Rouse model in nanoslits and Zimm model in the bulk solution, respectively. We show that the conformation and chain relaxation of DNA confined in a slit close to Kuhn length exhibit the quasi-two-dimensional behavior.

Efficient light harvesting by sequential energy transfer across aggregates in polymers of finite conjugational segments with short aliphatic linkages.

Interactions between lumophores have a critical influence on the photophysical properties of conjugated polymers. We synthesized a new series of light-harvesting polymers (poly-DSBs, I-IV) of dialkyloxy- or dialkyl-substituted distyrylbenzene (the substituents being methoxy, 2-ethylhexyloxy, and cyclohexyl) with short aliphatic linkage (methylene or ethylene) and examined the effects of interactions between lumophores and of chemical structures on the absorption, emission, and excitation spectra. The proximity between distyrylbenzene lumophores was shown to be critical to the interactions between lumophores and to the energy-transfer processes. In concentrated solutions and solid films, intermolecular aggregates exist resulting from different extents of interactions between lumophores and are found to involve at least three species: loose, compact, and the most aligned aggregates as observed by photoluminescence and excitation spectroscopies. We also found, for the first time, sequential energy transfer from individual lumophores to the most compact, aligned aggregates via the looser intermolecular aggregates, as observed directly by time-resolved fluorescence spectroscopy. Such a process mimics energy transfer in photosynthesis units and is so efficient such that the fluorescence color can be red-shifted drastically by the presence of comparatively few aggregates and that the light evolved from concentrated solutions and films of poly-DSBs I-IV is entirely or almost the aggregation emission. Although the sequential energy-transfer process in fully conjugated electro-/photoluminescent polymers due to inhomogenity other than distributed conjugation lengths has never been directly observed at room temperature, we suggest that events similar to those observed in poly-DSBs in conjugated polymers could occur but on a much shorter time scale, i.e., a few picoseconds.

Soluble electroluminescent poly(phenylene vinylene)s with balanced electron- and hole injections.

We report a new route for the design of efficient soluble electroluminescent PPV-based copolymers bearing electron-deficient oxadiazole (OXD) moieties on side chains. The introduction of OXD through a long alkylene spacer with PPV backbone provides a molecular dispersion of OXD in the film; both the side chain OXD and the main chain PPV do retain their own electron-transport and emissive properties, respectively. The use of phenylene vinylene derivatives with asymmetric and branched substituents and a long spacer provides solubility for ease of device fabrication as well as amorphous structure to allow a well-mixing of OXD groups with the main chains. By properly adjusting the OXD content through copolymerization, we can tailor the chemical structure of electroluminescent material to give a balance of hole- and electron injections for various metal cathodes, such that the quantum efficiency is significantly improved and the turn-on voltage is reduced for the devices with aluminum and calcium. For the device with calcium fabricated in open air, a maximum brightness of 15000 cd/m(2) at 15 V/100 nm and a maximum luminance efficiency of 2.27 cd/A can be obtained, respectively, about 30 times brighter and 9.4 times more efficient than those with the corresponding homopolymer, poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV). The use of physical blends to simulate the copolymers provides no significant improvement, since phase-separation structures appear, causing an inefficient utilization of OXD and sometimes voltage-dependent emission spectra. The present route permits a fabrication of single layer PLED with high brightness, high efficiency, and low turn-on voltage.

The correlation between polarization modulated near-field optical images and the anisotropy of the probe.

The true anisotropic images taken with the polarization modulation near-field optical microscope are often influenced by the linear dichroism of the tapered fibre probe. In this paper, we develop a new method to separate the anisotropic image form probe's dichroism. Our calculations show that the near-field optical image is simply a vector sum of the sample's dichroism and the probe's dichroism, when the probe's anisotropy is small. With this result, we demonstrate the true anisotropic images of poly(phenylene vinylene) (PPV) thin films. The PPV films show non-uniform mesoscale dichroic domains with average domain size, approximately 0.3 mm, and the coefficient for linear dichroism is 1.25 x 10(4) cm(-1).

Near-field scanner for moving molecules.

We have fabricated using electron beam nanolithography a fixed slit near-field optical scanning device which uses near-field fluorimetry to achieve 200 nm spatial resolution of objects moving over the slits. We explore the basic physics of operating narrow slits in the waveguide cutoff mode and present data from the passage of extended double-stranded DNA molecules passing over the slits as a first example of how this device can be used to do ultrahigh spatial resolution mapping of long polymers.

Interactions between hydrophobic and hydrophilic silicon surfaces using a tapered probe in near-field scanning optical microscopy.

We examined the tip-sample interaction of a Si(111) surface processed with HF solution. The interaction length of the probe with its hydrophobic surface is approximately 30, and the frequency responses show an interaction force of elastic type. By contrast, the damping curve on a hydrophilic surface, Si with thin oxide, operates on a longer length of 100. Here, the frequency responses indicate an interaction force of the viscous type.

Effect of D57N mutation on membrane activity and molecular unfolding of cobra cardiotoxin.

Cobra cardiotoxins (CTXs) are able to adopt a three-fingered beta-strand structure with continuous hydrophobic patch that is capable of interacting with zwitterionic phospholipid bilayer. In addition to the four disulfide bonds that form the rigid core of CTXs, Asp57 near the C-terminus interacts electrostatically with Lys2 near the N-terminus (Chiang et al. 1996. Biochemistry. 35:9177-9186). We indicate herein, using circular dichroism and the time-resolved polarized tryptophan fluorescence measurement, that Asp57 to Asn57 (D57N) mutation perturbs the structure of CTX molecules at neutral pH. The structural stability of the D57N mutant was found to be lower, as evidenced by the reduced effective concentration of the 2,2,2-trifluoethanol (TFE)-induced beta-sheet to alpha-helix transition. Interestingly, the single mutation also allows a greater degree of molecular unfolding, because the rotational correlation time of the TFE-induced unfolding intermediate is larger for the D57N mutant. It is suggested that the electrostatic interaction between N- and C-termini also contributes to the formation of the functionally important continuous hydrophobic stretch on the distant end of CTX molecules, because both the binding to anilinonaphthalene fluorescent probe and the interaction with phospholipid bilayer were also reduced for D57N mutant. The result emphasizes the importance of the hydrophobic amino acid residues near the tip of loop 3 as a continuous part of the three-fingered beta-strand CTX molecule and indicates how a distant electrostatic interaction might be involved. It is also implicated that electrostatic interaction plays a role in expanding the radius of gyration of the folding/unfolding intermediate of proteins.

Phase separation in polyaniline with near-field scanning optical microscopy.

We report the studies of conjugated polymers, polyaniline thin films, with a near-field scanning optical microscope. Because of the absorption variation in different oxidation states, transmission-mode near-field scanning optical microscope images were employed to map out the distribution of the oxidation states on a submicrometer scale. When the near-field wavelength is varied (between 632.8 and 543.5 nm), the phase separation between the oxidized and the reduced repeated units, with domain sizes on a nanometer-length scale, is observed.

Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples.

Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed.

Two-dimensional near-field intensity distribution of tapered fiber probes.

The near-field intensity distribution perpendicular to the light-propagation direction was measured by photochemical processes on conjugated-polymer thin films. The shape of the distribution is elliptical, with the long axis along the direction of the incident polarization. The results are compared with calculations based on the realistic tapered probe geometry. The asymmetry distribution is due to the simultaneous presence of horizontal and vertical electric fields in the near field.

Dual-optical-mode near-field scanning optical microscopy.

The simultaneous operation of near-field scanning optical microscopy (NSOM) in reflection and transmission modes is demonstrated. In the transmission mode, a low-noise, large-area silicon photodetector was mounted between the piezoelectric transducer scanning stage and the sample. In the reflection mode, either a photomultiplier tube or two large-area silicon detectors was used for signal collection. The reflection-mode setup consisting of two silicon detectors provides a large numerical aperture of 0.9 as well as symmetrical detection of emitting photons. The dielectric thin films and the light-emitting polymers were used to demonstrate the capability of these two modes of NSOM. A comparison between these two different setups is also presented.

Association between genetic variation at the porphobilinogen deaminase gene and schizophrenia.

There is growing evidence that some genetic predisposition is important in the etiology of schizophrenia. We have sought to implicate a major gene by performing a candidate gene association study comparing the allele frequencies of seven restriction fragment length polymorphisms (RFLPs) at six loci in both a psychiatrically normal control group (N = 51) and an affected (schizophrenia or schizoaffective disorder) group (N = 55). Each group comprised Caucasians of northern European origin. The candidate areas (D5S39, D5S78, dopamine receptor D2 (DRD2), D11S29, porphobilinogen deaminase (PBGD), and D11S84) were selected on the basis of prior cytogenetic findings in schizophrenics, linkage studies, and/or implicated gene products. The presence of a polymorphic ApaLI site within the PBGD gene showed a significant association with the presence of illness (P = 0.02). The relative risk of possessing the allele with the ApaLI site was 2.10. No significant association was found with any of the six other RFLPs. Our data suggests that either the PBGD gene itself or an unknown gene linked to and/or in linkage disequilibrium with the PBGD locus predisposes some individuals to schizophrenia. Independent replication of these findings will be required to determine their relevance to schizophrenia.