Superhigh-frequency characteristics of optical modulators on the basis of InGaAlAs resonance-tunnel heterostructures

The impedance of InGaAlAs resonance-tunnel heterostructures used for modulation of optical radiation is experimentally studied in the frequency range from 45 to 18 MHz. The dependence of their equivalent circuit on the bias voltage is determined. The spectrum of the harmonics of the current in the resistive frequency multiplication in such structures is calculated. The results confirm that these structures are promising as applied to the frequency multiplication. The effect of frequency multiplication is demonstrated experimentally at low frequencies

Atomic Force Microscopy of DNA, Nucleoproteins and Cellular Complexes: The Use of Functionalized Substrates

Progress towards rapid and simple characterization of biomolecular samples by scanning probe microscopy is impeded mainly by limitations of the current approach to sample preparation. We are working on approaches based on chemical functionalization of mica. Treatment of mica with aminopropyltriethoxy silane (APTES) makes the surface positively charged (AP-mica) and able to hold DNA in place for imaging, even in water. We have shown that AP-mica is an appropriate substrate for numerous nucleoprotein complexes as well. The AFM images of the complex of DNA with RecA protein are stable and indicate a structural periodicity for this filament. AP-mica holds strongly such large DNA complexes as kinetoplast DNA (kDNA) and is an appropriate substrate for their imaging with AFM. We have further develop this approach for making hydrophobic substrates. Silylation of mica surface with hexamethyldisilazane (Me-mica) allowed us to get AFM images of chlorosomes, an antenna complex isolated from green photosynthetic bacteria. Me-mica may be converted into a positively charged substrate after treatment with water solutions of tetraethylammonium bromide or cetyltrimethylammonium bromide. These activated surfaces show high activity towards binding the DNA molecules

Bubbles, clusters and denaturation in genomic DNA: modeling, parametrization, efficient computation

The paper uses mesoscopic, non-linear lattice dynamics based (Peyrard-Bishop-Dauxois, PBD) modeling to describe thermal properties of DNA below and near the denaturation temperature. Computationally efficient notation is introduced for the relevant statistical mechanics. Computed melting profiles of long and short heterogeneous sequences are presented, using a recently introduced reparametrization of the PBD model, and critically discussed. The statistics of extended open bubbles and bound clusters is formulated and results are presented for selected examples.Comment: to appear in a special issue of the Journal of Nonlinear Mathematical Physics (ed. G. Gaeta

Giant suppression of shot noise as signature of coherent transport in double barrier resonant diodes

Shot noise suppression in double barrier resonant tunnelling diodes with a Fano factor well below the value of 0.5 is theoretically predicted. This giant suppression is found to be a signature of the coherent transport regime and can occur near zero temperature as a consequence of the Pauli principle or above about 77 K as a consequence of long range Coulomb interaction. These predictions are validated by experimental data

Coherent approach to transport and noise in double-barrier resonant diodes

We implement a quantum approach which includes long range Coulomb interaction and investigate current voltage characteristics and shot noise in double-barrier resonant diodes. The theory applies to the region of low applied voltages up to the region of the current peak and considers the wide temperature range from zero to room temperature. The shape of the current voltage characteristic is well reproduced and we confirm that even in the presence of Coulomb interaction the shot noise can be suppressed with a Fano factor well below the value of 0.5. This feature can be an indication of coherent tunneling since the standard sequential tunneling predicts in general a Fano factor equal to or greater than the value 0.5. This giant suppression is a consequence of Pauli principle as well as long range Coulomb interaction. The theory generalizes previous findings and is compared with experiments

Giant suppression of shot noise in double barrier resonant diode: a signature of coherent transport

Shot noise suppression in double barrier resonant tunnelling diodes with a Fano factor well below the value of 0.5 is theoretically predicted. This giant suppression is found to be a signature of coherent transport regime and can occur at zero temperature as a consequence of the Pauli principle or at sufficiently high temperatures above 77 K as a consequence of a long-range Coulomb interaction. These predictions are in agreement with experimental data

Au-Ag template stripped pattern for scanning probe investigations of DNA arrays produced by Dip Pen Nanolithography

We report on DNA arrays produced by Dip Pen Nanolithography (DPN) on a novel Au-Ag micro patterned template stripped surface. DNA arrays have been investigated by atomic force microscopy (AFM) and scanning tunnelling microscopy (STM) showing that the patterned template stripped substrate enables easy retrieval of the DPN-functionalized zone with a standard optical microscope permitting a multi-instrument and multi-technique local detection and analysis. Moreover the smooth surface of the Au squares (abput 5-10 angstrom roughness) allows to be sensitive to the hybridization of the oligonucleotide array with label-free target DNA. Our Au-Ag substrates, combining the retrieving capabilities of the patterned surface with the smoothness of the template stripped technique, are candidates for the investigation of DPN nanostructures and for the development of label free detection methods for DNA nanoarrays based on the use of scanning probes.Comment: Langmuir (accepted

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Physicochemical characteristics of soluble oligomeric A β and their pathologic role in Alzheimer's disease

Extracellular fibrillar amyloid deposits are prominent and universal Alzheimer's disease (AD) features, but senile plaque abundance does not always correlate directly with the degree of dementia exhibited by AD patients. The mechanism(s) and dynamics of Abeta fibril genesis and deposition remain obscure. Enhanced Abeta synthesis rates coupled with decreased degradative enzyme production and accumulating physical modifications that dampen proteolysis may all enhance amyloid deposit formation. Amyloid accumulation may indirectly exert the greatest pathologic effect on the brain vasculature by destroying smooth muscle cells and creating a cascade of negative impacts on cerebral blood flow. The most visible manifestation of amyloid dis-equilibrium could actually be a defense mechanism employed to avoid serious vascular wall degradation while the major toxic effects to the gray and white matter neurons are mediated by soluble oligomeric Abeta peptides with high beta-sheet content. The recognition that dynamic soluble oligomeric Abeta pools exist in AD and are correlated to disease severity led to neurotoxicity and physical conformation studies. It is now recognized that the most basic soluble Abeta peptides are stable dimers with hydrophobic regions sequestered from the aqueous environment and are capable of higher order aggregations. Time course experiments employing a modified ELISA method able to detect Abeta oligomers revealed dynamic intermolecular interactions and additional experiments physically confirmed the presence of stable amyloid multimers. Amyloid peptides that are rich in beta-sheet structure are capable of creating toxic membrane ion channels and a capacity to self-assemble as annular structures was confirmed in vitro using atomic force microscopy. Biochemical studies have established that soluble Abeta peptides perturb metabolic processes, provoke release of deleterious reactive compounds, reduce blood flow, induce mitochondrial apoptotic toxicity and inhibit angiogenesis. While there is no question that gross amyloid deposition does contribute to AD pathology, the destructive potential now associated with soluble Abeta suggests that treatment strategies that target these molecules may be efficacious in preventing some of the devastating effects of AD.Fil: Watson, Desiree. Pfizer Global Research and Development; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Kokjohn, Tyler A.. Midwestern University; Estados UnidosFil: Kuo, Yu Min. National Cheng Kung University; República de ChinaFil: Lyubchenko, Yuri. University of Nebrasca; Estados UnidosFil: Pinsky, David. University of Michigan; Estados UnidosFil: Connolly, E. Sander. Columbia University; Estados UnidosFil: Esh, Chera. Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Stine, W. Blaine. Midwestern University; Estados UnidosFil: Rowse, Linda M.. Midwestern University; Estados UnidosFil: Emmerling, Mark R.. Midwestern University; Estados UnidosFil: Roher, Alex E.. Sun Health Research Institute; Estados Unido