627 research outputs found
Thermodynamic approach to the dewetting instability in ultrathin films
The fluid dynamics of the classical dewetting instability in ultrathin films
is a non-linear process. However, the physical manifestation of the instability
in terms of characteristic length and time scales can be described by a
linearized form of the initial conditions of the films's dynamics. Alternately,
the thermodynamic approach based on equating the rate of free energy decrease
to the viscous dissipation [de Gennes, C. R. Acad. Paris.v298, 1984] can give
similar information. Here we have evaluated dewetting in the presence of
thermocapillary forces arising from a film-thickness (h) dependent temperature.
Such a situation can be found during pulsed laser melting of ultrathin metal
films where nanoscale effects lead to a local h-dependent temperature. The
thermodynamic approach provides an analytical description of this
thermocapillary dewetting. The results of this approach agree with those from
linear theory and experimental observations provided the minimum value of
viscous dissipation is equated to the rate of free energy decrease. The flow
boundary condition that produces this minimum viscous dissipation is when the
film-substrate tangential stress is zero. The physical implication of this
finding is that the spontaneous dewetting instability follows the path of
minimum rate of energy loss.Comment: 8 pages, 3 figures. Under revie
Robust nanopatterning by laser-induced dewetting of metal nanofilms
We have observed nanopattern formation with robust and controllable spatial
ordering by laser-induced dewetting in nanoscopic metal films. Pattern
evolution in Co film of thickness 1\leq h\leq8 nm on SiO_{2} was achieved under
multiple pulse irradiation using a 9 ns pulse laser. Dewetting leads to the
formation of cellular patterns which evolve into polygons that eventually break
up into nanoparticles with monomodal size distribution and short range ordering
in nearest-neighbour spacing R. Spatial ordering was attributed to a
hydrodynamic thin film instability and resulted in a predictable variation of R
and particle diameter D with h. The length scales R and D were found to be
independent of the laser energy. These results suggest that spatially ordered
metal nanoparticles can be robustly assembled by laser-induced dewetting
Self consistent determination of plasmonic resonances in ternary nanocomposites
We have developed a self consistent technique to predict the behavior of
plasmon resonances in multi-component systems as a function of wavelength. This
approach, based on the tight lower bounds of the Bergman-Milton formulation, is
able to predict experimental optical data, including the positions, shifts and
shapes of plasmonic peaks in ternary nanocomposites without using any ftting
parameters. Our approach is based on viewing the mixing of 3 components as the
mixing of 2 binary mixtures, each in the same host. We obtained excellent
predictions of the experimental optical behavior for mixtures of Ag:Cu:SiO2 and
alloys of Au-Cu:SiO2 and Ag-Au:H2 O, suggesting that the essential physics of
plasmonic behavior is captured by this approach.Comment: 7 pages and 4 figure
Thickness-dependent spontaneous dewetting morphology of ultrathin Ag films
We show here that the morphological pathway of spontaneous dewetting of
ultrathin Ag films on SiO2 under nanosecond laser melting is found to be film
thickness dependent. For films with thickness h between 2 <= h <= 9.5 nm, the
morphology during the intermediate stages of dewetting consisted of
bicontinuous structures. For films 11.5 <= h <= 20 nm, the intermediate stages
consisted of regularly-sized holes. Measurement of the characteristic length
scales for different stages of dewetting as a function of film thickness showed
a systematic increase, which is consistent with the spinodal dewetting
instability over the entire thickness range investigated. This change in
morphology with thickness is consistent with observations made previously for
polymer films [A. Sharma et al, Phys. Rev. Lett., v81, pp3463 (1998); R.
Seemann et al, J. Phys. Cond. Matt., v13, pp4925, (2001)]. Based on the
behavior of free energy curvature that incorporates intermolecular forces, we
have estimated the morphological transition thickness for the intermolecular
forces for Ag on SiO2 . The theory predictions agree well with observations for
Ag. These results show that it is possible to form a variety of complex Ag
nanomorphologies in a consistent manner, which could be useful in optical
applications of Ag surfaces, such as in surface enhanced Raman sensing.Comment: 20 pages, 5 figure
Global gene expression in neuroendocrine tumors from patients with the MEN1 syndrome
BACKGROUND: Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100) is an autosomal dominant disorder characterized by endocrine tumors of the parathyroids, pancreatic islets and pituitary. The disease is caused by the functional loss of the tumor suppressor protein menin, coded by the MEN1 gene. The protein sequence has no significant homology to known consensus motifs. In vitro studies have shown menin binding to JunD, Pem, Smad3, NF-kappaB, nm23H1, and RPA2 proteins. However, none of these binding studies have led to a convincing theory of how loss-of-menin leads to neoplasia. RESULTS: Global gene expression studies on eight neuroendocrine tumors from MEN1 patients and 4 normal islet controls was performed utilizing Affymetrix U95Av2 chips. Overall hierarchical clustering placed all tumors in one group separate from the group of normal islets. Within the group of tumors, those of the same type were mostly clustered together. The clustering analysis also revealed 19 apoptosis-related genes that were under-expressed in the group of tumors. There were 193 genes that were increased/decreased by at least 2-fold in the tumors relative to the normal islets and that had a t-test significance value of p < = 0.005. Forty-five of these genes were increased and 148 were decreased in the tumors relative to the controls. One hundred and four of the genes could be classified as being involved in cell growth, cell death, or signal transduction. The results from 11 genes were selected for validation by quantitative RT-PCR. The average correlation coefficient was 0.655 (range 0.235–0.964). CONCLUSION: This is the first analysis of global gene expression in MEN1-associated neuroendocrine tumors. Many genes were identified which were differentially expressed in neuroendocrine tumors arising in patients with the MEN1 syndrome, as compared with normal human islet cells. The expression of a group of apoptosis-related genes was significantly suppressed, suggesting that these genes may play crucial roles in tumorigenesis in this syndrome. We identified a number of genes which are attractive candidates for further investigation into the mechanisms by which menin loss causes tumors in pancreatic islets. Of particular interest are: FGF9 which may stimulate the growth of prostate cancer, brain cancer and endometrium; and IER3 (IEX-1), PHLDA2 (TSS3), IAPP (amylin), and SST, all of which may play roles in apoptosis
Investigation of pulsed laser induced dewetting in nanoscopic metal films
Hydrodynamic pattern formation (PF) and dewetting resulting from pulsed laser
induced melting of nanoscopic metal films have been used to create spatially
ordered metal nanoparticle arrays with monomodal size distribution on
SiO_{\text{2}}/Si substrates. PF was investigated for film thickness h\leq7 nm
< laser absorption depth \sim11 nm and different sets of laser parameters,
including energy density E and the irradiation time, as measured by the number
of pulses n. PF was only observed to occur for E\geq E_{m}, where E_{m} denotes
the h-dependent threshold energy required to melt the film. Even at such small
length scales, theoretical predictions for E_{m} obtained from a
continuum-level lumped parameter heat transfer model for the film temperature,
coupled with the 1-D transient heat equation for the substrate phase, were
consistent with experimental observations provided that the thickness
dependence of the reflectivity of the metal-substrate bilayer was incorporated
into the analysis. The spacing between the nanoparticles and the particle
diameter were found to increase as h^{2} and h^{5/3} respectively, which is
consistent with the predictions of the thin film hydrodynamic (TFH) dewetting
theory. These results suggest that fast thermal processing can lead to novel
pattern formation, including quenching of a wide range of length scales and
morphologies.Comment: 36 pages, 11 figures, 1 tabl
Novel Iron-based ternary amorphous oxide semiconductor with very high transparency, electronic conductivity, and mobility
Here we report that ternary metal oxides of type (Me)2O3 with the primary metal (Me) constituent being Fe (66 atomic (at.) %) along with the two Lanthanide elements Tb (10 at.%) and Dy (24 at.%) can show excellent semiconducting transport properties. Thin films prepared by pulsed laser deposition at room temperature followed by ambient oxidation showed very high electronic conductivity (\u3e5 × 104 S/m) and Hall mobility (\u3e30 cm2/V-s). These films had an amorphous microstructure which was stable to at least 500 °C and large optical transparency with a direct band gap of 2.85 ± 0.14 eV. This material shows emergent semiconducting behavior with significantly higher conductivity and mobility than the constituent insulating oxides. Since these results demonstrate a new way to modify the behaviors of transition metal oxides made from unfilled d- and/or f-subshells, a new class of functional transparent conducting oxide materials could be envisioned
A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: Potential impact on CTL epitopes
The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates involving a total of 976 Vpr sequences. The polymorphisms at the individual amino acid level were analyzed. The residues 9, 33, 39, and 47 showed a single variant amino acid compared to other residues. There are several amino acids which are highly polymorphic. The residues that show ten or more variant amino acids are 15, 16, 28, 36, 37, 48, 55, 58, 59, 77, 84, 86, 89, and 93. Further, the variant amino acids noted at residues 60, 61, 34, 71 and 72 are identical. Interestingly, the frequency of the variant amino acids was found to be low for most residues. Vpr is known to contain multiple CTL epitopes like protease, reverse transcriptase, Env, and Gag proteins of HIV-1. Based on this, we have also extended our analysis of the amino acid polymorphisms to the experimentally defined and predicted CTL epitopes. The results suggest that amino acid polymorphisms may contribute to the immune escape of the virus. The available data on naturally occurring polymorphisms will be useful to assess their potential effect on the structural and functional constraints of Vpr and also on the fitness of HIV-1 for replication
Using the MitoB method to assess levels of reactive oxygen species in ecological studies of oxidative stress
In recent years evolutionary ecologists have become increasingly interested in the effects of reactive
oxygen species (ROS) on the life-histories of animals. ROS levels have mostly been inferred indirectly
due to the limitations of estimating ROS from in vitro methods. However, measuring ROS (hydrogen
peroxide, H2O2) content in vivo is now possible using the MitoB probe. Here, we extend and refine
the MitoB method to make it suitable for ecological studies of oxidative stress using the brown trout
Salmo trutta as model. The MitoB method allows an evaluation of H2O2 levels in living organisms over
a timescale from hours to days. The method is flexible with regard to the duration of exposure and
initial concentration of the MitoB probe, and there is no transfer of the MitoB probe between fish. H2O2
levels were consistent across subsamples of the same liver but differed between muscle subsamples
and between tissues of the same animal. The MitoB method provides a convenient method for
measuring ROS levels in living animals over a significant period of time. Given its wide range of possible
applications, it opens the opportunity to study the role of ROS in mediating life history trade-offs in
ecological settings
Mito-metformin protects against mitochondrial dysfunction and dopaminergic neuronal degeneration by activating upstream PKD1 signaling in cell culture and MitoPark animal models of Parkinson’s disease
Impaired mitochondrial function and biogenesis have strongly been implicated in the pathogenesis of Parkinson’s disease (PD). Thus, identifying the key signaling mechanisms regulating mitochondrial biogenesis is crucial to developing new treatment strategies for PD. We previously reported that protein kinase D1 (PKD1) activation protects against neuronal cell death in PD models by regulating mitochondrial biogenesis. To further harness the translational drug discovery potential of targeting PKD1-mediated neuroprotective signaling, we synthesized mito-metformin (Mito-Met), a mitochondria-targeted analog derived from conjugating the anti-diabetic drug metformin with a triphenylphosphonium functional group, and then evaluated the preclinical efficacy of Mito-Met in cell culture and MitoPark animal models of PD. Mito-Met (100–300 nM) significantly activated PKD1 phosphorylation, as well as downstream Akt and AMPKα phosphorylation, more potently than metformin, in N27 dopaminergic neuronal cells. Furthermore, treatment with Mito-Met upregulated the mRNA and protein expression of mitochondrial transcription factor A (TFAM) implying that Mito-Met can promote mitochondrial biogenesis. Interestingly, Mito-Met significantly increased mitochondrial bioenergetics capacity in N27 dopaminergic cells. Mito-Met also reduced mitochondrial fragmentation induced by the Parkinsonian neurotoxicant MPP+ in N27 cells and protected against MPP+-induced TH-positive neurite loss in primary neurons. More importantly, Mito-Met treatment (10 mg/kg, oral gavage for 8 week) significantly improved motor deficits and reduced striatal dopamine depletion in MitoPark mice. Taken together, our results demonstrate that Mito-Met possesses profound neuroprotective effects in both in vitro and in vivo models of PD, suggesting that pharmacological activation of PKD1 signaling could be a novel neuroprotective translational strategy in PD and other related neurocognitive diseases
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