Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications

Growth of GaN films on porous SiC substrate by molecular-beam epitaxy

Porous SiC (PSiC) substrates were used for the growth of GaN by reactive molecular-beam epitaxy with ammonia as the nitrogen source. Improved quality of GaNfilms has been demonstrated for growth on PSiC substrates, as compared to that on standard 6H–SiC substrates. Cross-sectional transmission electron microscopy and electron diffraction showed a reduction in dislocation density and a higher degree of lattice and thermal relaxation in the GaNfilmsgrown on porous substrates. The submicron GaNfilms exhibit a rocking curve linewidth of 3.3 arcmin for (0002) diffraction and 13.7 arcmin for (101̄2) diffraction. Low-temperature photoluminescence showed an excitonic transition with a full width at half maximum of 9.5 meV at 15 K, as well as high quantum efficiency, on the GaN layer grown on PSiC when the thin skin layer on porous SiC was removed before growth

Increased central auditory gain and decreased parvalbumin-positive cortical interneuron density in the Df1/+ mouse model of schizophrenia correlate with hearing impairment

Background Hearing impairment is a risk factor for schizophrenia. Patients with 22q11.2 Deletion Syndrome (22q11.2DS) have a 25-30% risk of schizophrenia, and up to 60% also have varying degrees of hearing impairment, primarily from middle ear inflammation. The Df1/+ mouse model of 22q11.2DS recapitulates many features of the human syndrome, including schizophrenia-relevant brain abnormalities and high inter-individual variation in hearing ability. However, the relationship between brain abnormalities and hearing impairment in Df1/+ mice has not been examined. Methods We measured auditory brainstem responses (ABRs), cortical auditory evoked potentials, and/or cortical parvalbumin-positive (PV+) interneuron density in over 70 adult mice (32 Df1/+, 39 wild-type). We also performed longitudinal ABR measurements in an additional 20 animals (13 Df1/+, 7 wild-type) from 3 weeks of age. Results Electrophysiological markers of central auditory excitability were elevated in Df1/+ mice. PV+ interneurons, which are implicated in schizophrenia pathology, were reduced in density in auditory cortex but not secondary motor cortex. Both auditory brain abnormalities correlated with hearing impairment, which affected approximately 60% of adult Df1/+ mice and typically emerged before 6 weeks of age. Conclusions In the Df1/+ mouse model of 22q11.2DS, abnormalities in central auditory excitability and auditory cortical PV+ immunoreactivity correlate with hearing impairment. This is the first demonstration of cortical PV+ interneuron abnormalities correlating with hearing impairment in a mouse model of either schizophrenia or middle ear inflammation

Effectiveness of TiN porous templates on the reduction of threading dislocations in GaN overgrowth by organometallic vapor-phase epitaxy

We report on the reduction of threading dislocations in GaN overlayers grown by organometallic vapor phase epitaxy on micro-porous TiN networks. These networks were obtained by in situannealing of thin Ti layers deposited in a metalization chamber, on the (0001) face of GaN templates. Observations by transmission electron microscopy indicate dislocation reduction by factors of up to 10 in GaN layers grown on TiN networks compared with the control GaN.X-ray diffraction shows that GaNgrown on the TiN network has a smaller (102) plane peak width (4.6 arcmin) than the control GaN (7.8 arcmin). In low temperature photoluminescence spectra, a narrow excitonic full-width-at-half-maximum of 2.4 meV was obtained, as compared to 3.0 meV for the control GaN, confirming the improved crystalline quality of the overgrown GaN layers

Is mindfulness Buddhist? (and why it matters).

Modern exponents of mindfulness meditation promote the therapeutic effects of "bare attention"--a sort of non-judgmental, non-discursive attending to the moment-to-moment flow of consciousness. This approach to Buddhist meditation can be traced to Burmese Buddhist reform movements of the first half of the 20th century, and is arguably at odds with more traditional Theravāda Buddhist doctrine and meditative practices. But the cultivation of present-centered awareness is not without precedent in Buddhist history; similar innovations arose in medieval Chinese Zen (Chan) and Tibetan Dzogchen. These movements have several things in common. In each case the reforms were, in part, attempts to render Buddhist practice and insight accessible to laypersons unfamiliar with Buddhist philosophy and/or unwilling to adopt a renunciatory lifestyle. In addition, these movements all promised astonishingly quick results. And finally, the innovations in practice were met with suspicion and criticism from traditional Buddhist quarters. Those interested in the therapeutic effects of mindfulness and bare attention are often not aware of the existence, much less the content, of the controversies surrounding these practices in Asian Buddhist history

Aspects of Scalar Field Dynamics in Gauss-Bonnet Brane Worlds

The Einstein-Gauss-Bonnet equations projected from the bulk to brane lead to a complicated Friedmann equation which simplifies to $H^2 \sim \rho^q$ in the asymptotic regimes. The Randall-Sundrum (RS) scenario corresponds to $q=2$ whereas $q=2/3$ & $q=1$ give rise to high energy Gauss-Bonnet (GB) regime and the standard GR respectively. Amazingly, while evolving from RS regime to high energy GB limit, one passes through a GR like region which has important implications for brane world inflation. For tachyon GB inflation with potentials $V(\phi) \sim \phi^p$ investigated in this paper, the scalar to tensor ratio of perturbations $R$ is maximum around the RS region and is generally suppressed in the high energy regime for the positive values of $p$. The ratio is very low for $p>0$ at all energy scales relative to GB inflation with ordinary scalar field. The models based upon tachyon inflation with polynomial type of potentials with generic positive values of $p$ turn out to be in the $1 \sigma$ observational contour bound at all energy scales varying from GR to high energy GB limit. The spectral index $n_S$ improves for the lower values of $p$ and approaches its scale invariant limit for $p=-2$ in the high energy GB regime. The ratio $R$ also remains small for large negative values of $p$, however, difference arises for models close to scale invariance limit. In this case, the tensor to scale ratio is large in the GB regime whereas it is suppressed in the intermediate region between RS and GB. Within the frame work of patch cosmologies governed by $H^2 \sim \rho^q$, the behavior of ordinary scalar field near cosmological singularity and the nature of scaling solutions are distinguished for the values of $q 1$.Comment: 15 pages, 10 eps figures; appendix on various scales in GB brane world included and references updated; final version to appear in PR

Theory of Transmission through disordered superlattices

We derive a theory for transmission through disordered finite superlattices in which the interface roughness scattering is treated by disorder averaging. This procedure permits efficient calculation of the transmission thr ough samples with large cross-sections. These calculations can be performed utilizing either the Keldysh or the Landauer-B\"uttiker transmission formalisms, both of which yield identical equations. For energies close to the lowest miniband, we demonstrate the accuracy of the computationally efficient Wannier-function approximation. Our calculations indicate that the transmission is strongly affected by interface roughness and that information about scale and size of the imperfections can be obtained from transmission data.Comment: 12 pages, 6 Figures included into the text. Final version with minor changes. Accepted by Physical Review

An interferometric study of the low-mass protostar IRAS 16293-2422: small scale organic chemistry

Aims: To investigate the chemical relations between complex organics based on their spatial distributions and excitation conditions in the low-mass young stellar objects IRAS 16293-2422 A and B. Methods: Interferometric observations with the Submillimeter Array have been performed at 5''x3'' resolution revealing emission lines of HNCO, CH3CN, CH2CO, CH3CHO and C2H5OH. Rotational temperatures are determined from rotational diagrams when a sufficient number of lines are detected. Results: Compact emission is detected for all species studied here. For HNCO and CH3CN it mostly arises from source A, CH2CO and C2H5OH have comparable strength for both sources and CH3CHO arises exclusively from source B. HNCO, CH3CN and CH3CHO have rotational temperatures >200 K. The (u,v)-visibility data reveal that HNCO also has extended cold emission. Conclusions: The abundances of the molecules studied here are very similar within factors of a few to those found in high-mass YSOs. Thus the chemistry between high- and low-mass objects appears to be independent of luminosity and cloud mass. Bigger abundance differences are seen between the A and B source. The HNCO abundance relative to CH3OH is ~4 times higher toward A, which may be due to a higher initial OCN- ice abundances in source A compared to B. Furthermore, not all oxygen-bearing species are co-existent. The different spatial behavior of CH2CO and C2H5OH compared with CH3CHO suggests that hydrogenation reactions on grain-surfaces are not sufficient to explain the observed gas phase abundances. Selective destruction of CH3CHO may result in the anti-coincidence of these species in source A. These results illustrate the power of interferometric compared with single dish data in terms of testing chemical models.Comment: 11 pages, 15 figures, accepeted by A&

Combined BIMA and OVRO observations of comet C/1999 S4 (LINEAR)

We present results from an observing campaign of the molecular content of the coma of comet C/1999 S4 (LINEAR) carried out jointly with the millimeter-arrays of the Berkeley-Illinois-Maryland Association (BIMA) and the Owens Valley Radio Observatory (OVRO). Using the BIMA array in autocorrelation (`single-dish') mode, we detected weak HCN J=1-0 emission from comet C/1999 S4 (LINEAR) at 14 +- 4 mK km/s averaged over the 143" beam. The three days over which emission was detected, 2000 July 21.9-24.2, immediately precede the reported full breakup of the nucleus of this comet. During this same period, we find an upper limit for HCN 1-0 of 144 mJy/beam km/s (203 mK km/s) in the 9"x12" synthesized beam of combined observations of BIMA and OVRO in cross-correlation (`imaging') mode. Together with reported values of HCN 1-0 emission in the 28" IRAM 30-meter beam, our data probe the spatial distribution of the HCN emission from radii of 1300 to 19,000 km. Using literature results of HCN excitation in cometary comae, we find that the relative line fluxes in the 12"x9", 28" and 143" beams are consistent with expectations for a nuclear source of HCN and expansion of the volatile gases and evaporating icy grains following a Haser model.Comment: 18 pages, 3 figures. Uses aastex. AJ in pres