Biomedical subjects

M Stopa

Publications and source records attributed to M Stopa.

At least 19 recordsLinked to original sources

PubMed2006

Negative Coulomb drag in a one-dimensional wire.

We observed negative Coulomb drag for parallel coupled quantum wires, in which electrons flow in the opposite directions between the wires. This only occurred under the conditions of strong correlation in the wires, that is, low density, high magnetic field, and low temperature, and cannot be addressed by a standard theory of momentum transfer. We propose a Coulomb drag model in which formation of a Wigner crystal state in the drag wire and a particle-like state in the drive wire is taken into account.

Journal Article↗

PubMed2006

Multipeak Kondo effect in one- and two-electron quantum dots.

We have fabricated a few-electron quantum dot that can be tuned down to zero electrons while maintaining strong coupling to the leads. Using a nearby quantum point contact as a charge sensor, we can determine the absolute number of electrons in the quantum dot. We find several sharp peaks in the differential conductance, occurring at both zero and finite source-drain bias, for the one- and two-electron quantum dot. We attribute the peaks at finite bias to a Kondo effect through excited states of the quantum dot and investigate the magnetic field dependence of these Kondo resonances.

Journal Article↗

PubMed2005

Single-electron delocalization in hybrid vertical-lateral double quantum dots.

We used a hybrid vertical-lateral double-dot device, consisting of laterally coupled vertical quantum dots, to measure the interdot tunnel coupling. By using nonlinear transport measurements of "Coulomb diamonds," we showed that an inherent asymmetry in the capacitances of the component dots influences the diamond slopes, thereby allowing for the determination of the dot through which the electron has passed. We used this technique to prepare a delocalized one-electron state and Heitler-London (HL) two-electron state, and we showed that the interdot tunnel coupling, which determines whether HL is the ground state, is tunable. This implies that our device may be useful for implementing two-electron spin entanglement.

Journal Article↗

PubMed2004

Electron-spin and electron-orbital dependence of the tunnel coupling in laterally coupled double vertical dots.

We employ a new laterally coupled, vertical double dot with a tunable tunnel-coupling gate in a parallel configuration to study the electron spin and orbital dependence of quantum mechanical tunnel coupling on the size of the honeycomb vertices in the small electron numbers regime. We find a transition from the weak coupling regime, where fluctuations in tunnel coupling due to varying electron configuration dominate the anticrossings, to a regime where the two dots coalesce. We apply a magnetic field to ascertain the orbital angular momenta of the Fermi surface eigenstates, which correlate with anticrossing size, and we identify spin pairs with congruent behavior.

Journal Article↗

PubMed2004

Single-dot spectroscopy via elastic single-electron tunneling through a pair of coupled quantum dots.

We study the electronic structure of a single self-assembled InAs quantum dot by probing elastic single-electron tunneling through a single pair of weakly coupled dots. In the region below pinch-off voltage, the nonlinear threshold voltage behavior provides electronic addition energies exactly as the linear, Coulomb blockade oscillation does. By analyzing it, we identify the s and the p shell addition spectrum for up to six electrons in the single InAs dot, i.e., one of the coupled dots. The evolution of the shell addition spectrum with magnetic field provides Fock-Darwin spectra of the s and p shells.

Journal Article↗

PubMed2003

Magnetically induced chessboard pattern in the conductance of a Kondo quantum dot.

We quantitatively describe the main features of the magnetically induced conductance modulation of a Kondo quantum dot-or chessboard pattern-in terms of a constant-interaction double quantum dot model. We show that the analogy with a double dot holds down to remarkably low magnetic fields. The analysis is extended by full 3D spin density functional calculations. Introducing an effective Kondo coupling parameter, the chessboard pattern is self-consistently computed as a function of magnetic field and electron number, which enables us to explain our experimental data quantitatively.

Journal Article↗

PubMed2002

Rectifying behavior in Coulomb blockades: charging rectifiers.

We introduce examples of tunneling and diffusive, Coulomb-regulated rectifiers based on the Coulomb blockade formalism in discrete and continuum systems, respectively. Nonlinearity of the interacting dynamics profoundly enhances the inherent asymmetry of the devices by reducing the Hilbert space of accessible states. The discrete charging rectifier is structurally similar to hybrid molecular electronic rectifiers, while the continuum-charging rectifier is based on a model of ionic flow through a pore (ion channel) with an artificial branch. The devices are formally related to ratchet systems with spatial periodicity replaced by a winding number: the current.

Journal Article↗

PubMed2001

Transforming growth factor beta signal transduction in hepatic stellate cells via Smad2/3 phosphorylation, a pathway that is abrogated during in vitro progression to myofibroblasts. TGFbeta signal transduction during transdifferentiation of hepatic stellate cells.

To current knowledge, transforming growth factor beta (TGFbeta) signaling is mandatory to establish liver fibrosis and various molecular interventions designed to affect the TGFbeta system were successfully used to inhibit fibrogenesis. Activated hepatic stellate cells (HSC), which are one important source of TGFbeta, are the major producers of extracellular matrix proteins in liver injury. We have previously shown that the TGFbeta response of this cell type is modulated during the transdifferentiation process. This work delineates the activation of TGFbeta downstream mediators, the Smads, in quiescent HSC and transdifferentiated myofibroblasts (MFB). The expression level of all Smads remained largely unchanged during this process. The response of HSC to TGFbeta, leading to, e.g., induction of alpha2 (I) collagen expression, is mediated by phosphorylation of Smad2 and Smad3 and subsequent nuclear translocation of a Smad containing complex. Neither TGFbeta-dependent nor endogenously phosphorylated Smad2/3 was detectable in comparable amounts in transdifferentiated MFB, indicating loss of TGFbeta sensitivity. Ectopic expression of Smad7 in HSC led to inhibition of Smad2 phosphorylation and abrogated TGFbeta response. In transdifferentiated MFB, expression of a constitutively active TGFbeta receptor I, but not treatment with TGFbeta1, resulted in transcriptional activation of a TGFbeta responsive promoter, thereby demonstrating completely restored TGFbeta signal transduction. Our data indicate that in contrast to a postulated mechanism of enduring autocrine TGFbeta signal transduction, early and late stages of HSC activation have to be distinguished, which is of importance for antifibrotic therapies.

3T3 Cells↗

PubMed2000

Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF-beta)-induced activation of Smad7. THE TGF-beta response element of the promoter requires functional Smad binding element and E-box sequences for transcriptional regulation.

Smad7 has recently been identified as a player that antagonizes transforming growth factor beta (TGF-beta) signals by acting downstream of TGF-beta receptors. TGF-beta rapidly induces expression of Smad7 mRNA in a variety of cell types, suggesting participation in a negative feedback loop to control TGF-beta responses. We have previously described the genomic locus of rat Smad7 including the promoter region. Here we report polymerase chain reaction cloning of the corresponding promoter regions of human and murine Smad7 genes and functional characterization of the rat Smad7 promoter. Using transient transfection experiments of HepG2 cells, we identified the TGF-beta response element within a strongly conserved region, containing a perfect Smad binding element (SBE; GTCTAGAC). Performing electrophoretic mobility shift assay and cotransfection experiments, we were able to delineate DNA-binding complexes and identified Smad3, Smad4, and Smad2. Mutation of the SBE completely abolished TGF-beta inducibility of Smad7 in HepG2 cells, indicating that this sequence is necessary for TGF-beta-induced transcription. Furthermore, a 3-base pair adjacent E-box is additionally essential for TGF-beta-dependent promoter activation and an overlapping AP1 site is also involved. We conclude that regulation of Smad7 transcription by TGF-beta is mediated via a specific constellation of recognition motifs localized around the SBE, which is conserved in human, rat, and murine genes.

Animals↗

PubMed2000

Genomic locus and promoter region of rat Smad7, an important antagonist of TGFbeta signaling.

SMAD proteins are essential components of the intracellular signaling pathways utilized by members of the transforming growth factor beta (TGFbeta) superfamily of growth factors. Certain SMAD proteins (Smad1, 2, 3, and 5) can act as regulated transcriptional activators. This process involves phosphorylation of these proteins by activated TGFbeta receptors. Recently, Smad6 and Smad7 were identified; they antagonize TGFbeta signaling by preventing the activation of signal-transducing SMAD complexes. TGFbeta rapidly induces the expression of Smad7 mRNA, suggesting participation of Smad7 in a negative feedback loop to control TGFbeta responses. Similarly, epidermal growth factor (EGF) and interferon gamma (IFN-gamma) have been reported to induce Smad7 expression. In a rat model system of liver fibrosis, TGFbeta inducibility of Smad7 is abrogated during transformation of hepatic stellate cells (HSC), indicating an important switch in transcriptional regulation of the gene. With the detailed characterization of the rat Smad7 genomic organization including the promoter region, we present the first identified Smad7 gene so far. The gene is composed of four exons separated by three introns covering a DNA region of about 30 kilobases (kb) in total. The major transcription start site is conserved between rat and mouse, and two polyadenylation signals were detected. In the promoter region, a potential CAGA box, a signal transducer and activator of transcription (STAT) factor-related recognition site, and different AP1 sites were identified, which could be the targets of TGFbeta, IFN-gamma, and EGF-dependent Smad7 transcription initiation.

Animals↗

PubMed1998

Myoid cells and neuroendocrine markers in myasthenic thymuses.

We have studied myoid cells in normal and myasthenic thymuses as well as in thymomas. For the presence of neuroendocrine markers-producing cells and identification of synaptophysin (Syn) the immunohistochemical method and immunoblot analysis were used. Myoid cells can be demonstrated in the thymus of myasthenic patients in high number. These cells occur in the vicinity of Hassall's bodies but also within them. Some regenerated Hassall's bodies displayed majority of myoid cells with their concentric arrangement around the centrally situated lacunar-like cell with nuclei of monocytogenic origin. Such phenomenon may suggest cooperation of myoid cells and their epithelial transitional forms with monocytogenic cells in various thymic hormone production. It is likely that myoid cells are the source of some thymic epithelial cells. According to some authors, thymomatous epithelial cells and skeletal muscle share a common epitope defined by a monoclonal antibody (mAb), whereas thymic epithelial cells possess acetylocholine receptor (AChR) on their surface. The epithelial cells of some thymomas express also desmin. In normal thymuses of children, Syn and chromogranin A (Chg A) were demonstrated in some cells of Hassall's bodies by immunohistochemical method. In addition, antibodies to Syn stained nerve structures surrounding the thymic blood vessels. In myasthenic thymuses, Syn expression was in cortical and medullary epithelial cells, in myoid cells and only scanty and focal in keratinized epithelial cells of Hassall's bodies. The epithelial cells of some thymomas also express Syn. In some thymuses of all groups investigated in this study Chg A was seen in single cells of Hassall's bodies and focally in cortical epithelial cells. Our results show that in normal thymuses of cardiac surgery patients and in the adult myasthenic thymuses antibody raised against Syn recognized protein with molecular weight of 48,000 but not normal (38,000) Syn. It remains to be elucidated if the overexpression of synaptophysin-like protein in myasthenic thymuses is a compensatory phenomenon to the defect in normal synaptic function.

Adult↗

PubMed1997

Effect of sphingomyelin and its metabolites on the activity of human recombinant PLC delta 1.

In an attempt to obtain sufficient quantities of pure phospholipase C delta 1 (PLC delta 1) necessary for structural and kinetic studies, human fibroblast PLC delta 1 was cloned in the pPROEX-1 vector, expressed in E. coli cells as a (6xHis) fusion protein and purified to homogeneity. From 11 of E. coli culture 21 mg of pure PLC delta 1 was obtained by a two-step purification procedure, which includes Ni(2+)-NAT agarose and Mono S cation exchange chromatography. Catalytic properties of recombinant PLC delta 1 with respect to activation by spermine and calcium ions and inhibition by sphingomyelin were similar to or identical to PLC delta 1 purified from rat liver. Calcium activation of PLC delta 1 was dependent on the presence of spermine. Half-maximal activity was attained at 250 and 170 nM of free Ca2+ in the presence and absence of spermine, respectively. Sphingomyelin and lysosphingomyelin were mixed type inhibitors with respect to PIP2. Ceramide inhibits PLC delta 1 very weakly. GM1, which is a ceramide bound glucosidically to the oligosaccharide moiety, was a strong non-competitive inhibitor of PLC delta 1. In the absence of spermine, sphingosine and phytosphingosine weakly activated PLC delta 1. The results indicate that the effect of sphingomyelin and its metabolites on PLC delta 1 activity depends on the presence of spermine. It is postulated that, among other factors, in vivo, activity of PLC delta 1 may depend on the turnover of sphingomyelin.

Animals↗

PubMed1996