686 research outputs found
Quantum Coherence at Low Temperatures in Mesoscopic Systems: Effect of Disorder
We study the disorder dependence of the phase coherence time of quasi
one-dimensional wires and two-dimensional (2D) Hall bars fabricated from a high
mobility GaAs/AlGaAs heterostructure. Using an original ion implantation
technique, we can tune the intrinsic disorder felt by the 2D electron gas and
continuously vary the system from the semi-ballistic regime to the localized
one. In the diffusive regime, the phase coherence time follows a power law as a
function of diffusion coefficient as expected in the Fermi liquid theory,
without any sign of low temperature saturation. Surprisingly, in the
semi-ballistic regime, it becomes independent of the diffusion coefficient. In
the strongly localized regime we find a diverging phase coherence time with
decreasing temperature, however, with a smaller exponent compared to the weakly
localized regime.Comment: 21 pages, 30 figure
Pressure-induced phase transition of Bi2Te3 into the bcc structure
The pressure-induced phase transition of bismuth telluride, Bi2Te3, has been
studied by synchrotron x-ray diffraction measurements at room temperature using
a diamond-anvil cell (DAC) with loading pressures up to 29.8 GPa. We found a
high-pressure body-centered cubic (bcc) phase in Bi2Te3 at 25.2 GPa, which is
denoted as phase IV, and this phase apperars above 14.5 GPa. Upon releasing the
pressure from 29.8 GPa, the diffraction pattern changes with pressure
hysteresis. The original rhombohedral phase is recovered at 2.43 GPa. The bcc
structure can explain the phase IV peaks. We assumed that the structural model
of phase IV is analogous to a substitutional binary alloy; the Bi and Te atoms
are distributed in the bcc-lattice sites with space group Im-3m. The results of
Rietveld analysis based on this model agree well with both the experimental
data and calculated results. Therefore, the structure of phase IV in Bi2Te3 can
be explained by a solid solution with a bcc lattice in the Bi-Te (60 atomic%
tellurium) binary system.Comment: 12 pages, 5 figure
Sequential Logic Model Deciphers Dynamic Transcriptional Control of Gene Expressions
Cellular signaling involves a sequence of events from ligand binding to membrane receptors through transcription factors activation and the induction of mRNA expression. The transcriptional-regulatory system plays a pivotal role in the control of gene expression. A novel computational approach to the study of gene regulation circuits is presented here.Based on the concept of finite state machine, which provides a discrete view of gene regulation, a novel sequential logic model (SLM) is developed to decipher control mechanisms of dynamic transcriptional regulation of gene expressions. The SLM technique is also used to systematically analyze the dynamic function of transcriptional inputs, the dependency and cooperativity, such as synergy effect, among the binding sites with respect to when, how much and how fast the gene of interest is expressed. expression and additional activities of binding sites are required. Further analyses suggest detailed mechanism of R switch activity where indirect dependency occurs in between UI activity and R switch during specification to differentiation stage. is a promising step for further application of the proposed method
Angle-resolved photoemission study of insulating and metallic Cu-O chains in PrBaCuO and PrBaCuO
We compare the angle-resolved photoemission spectra of the hole-doped Cu-O
chains in PrBaCuO (Pr123) and in PrBaCuO (Pr124).
While, in Pr123, a dispersive feature from the chain takes a band maximum at
(momentum along the chain) and loses its spectral weight
around the Fermi level, it reaches the Fermi level at in
Pr124. Although the chains in Pr123 and Pr124 are approximately 1/4-filled,
they show contrasting behaviors: While the chains in Pr123 have an instability
to charge ordering, those in Pr124 avoid it and show an interesting spectral
feature of a metallic coupled-chain system.Comment: 4 pages, 5 figures, to be published in PR
Threshold-dominated regulation hides genetic variation in gene expression networks
<p>Abstract</p> <p>Background</p> <p>In dynamical models with feedback and sigmoidal response functions, some or all variables have thresholds around which they regulate themselves or other variables. A mathematical analysis has shown that when the dose-response functions approach binary or on/off responses, any variable with an equilibrium value close to one of its thresholds is very robust to parameter perturbations of a homeostatic state. We denote this threshold robustness. To check the empirical relevance of this phenomenon with response function steepnesses ranging from a near on/off response down to Michaelis-Menten conditions, we have performed a simulation study to investigate the degree of threshold robustness in models for a three-gene system with one downstream gene, using several logical input gates, but excluding models with positive feedback to avoid multistationarity. Varying parameter values representing functional genetic variation, we have analysed the coefficient of variation (<it>CV</it>) of the gene product concentrations in the stable state for the regulating genes in absolute terms and compared to the <it>CV </it>for the unregulating downstream gene. The sigmoidal or binary dose-response functions in these models can be considered as phenomenological models of the aggregated effects on protein or mRNA expression rates of all cellular reactions involved in gene expression.</p> <p>Results</p> <p>For all the models, threshold robustness increases with increasing response steepness. The <it>CV</it>s of the regulating genes are significantly smaller than for the unregulating gene, in particular for steep responses. The effect becomes less prominent as steepnesses approach Michaelis-Menten conditions. If the parameter perturbation shifts the equilibrium value too far away from threshold, the gene product is no longer an effective regulator and robustness is lost. Threshold robustness arises when a variable is an active regulator around its threshold, and this function is maintained by the feedback loop that the regulator necessarily takes part in and also is regulated by. In the present study all feedback loops are negative, and our results suggest that threshold robustness is maintained by negative feedback which necessarily exists in the homeostatic state.</p> <p>Conclusion</p> <p>Threshold robustness of a variable can be seen as its ability to maintain an active regulation around its threshold in a homeostatic state despite external perturbations. The feedback loop that the system necessarily possesses in this state, ensures that the robust variable is itself regulated and kept close to its threshold. Our results suggest that threshold regulation is a generic phenomenon in feedback-regulated networks with sigmoidal response functions, at least when there is no positive feedback. Threshold robustness in gene regulatory networks illustrates that hidden genetic variation can be explained by systemic properties of the genotype-phenotype map.</p
DNA topoisomerases participate in fragility of the oncogene RET
Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumours
Doxorubicin pharmacokinetics were determined in 33 patients with solid tumours who received intravenous doses of 20–320 mg m−2 HPMA copolymer bound doxorubicin (PK1) in a phase I study. Since assay constraints limited the data at lower doses, conventional analysis was not feasible and a ‘population approach’ was used. Bound concentrations were best described by a biexponential model and further analyses revealed a small influence of dose or weight on V1 but no identifiable effects of age, body surface area, renal or hepatic function. The final model was: clearance (Q) 0.194 l h−1; central compartment volume (V1) 4.48 × (1+0.00074 × dose (mg)) l; peripheral compartment volume (V2) 7.94 l; intercompartmental clearance 0.685 l h−1. Distribution and elimination half-lives had median estimates of 2.7 h and 49 h respectively. Free doxorubicin was present at most sampling times with concentrations around 1000 times lower than bound doxorubicin values. Data were best described using a biexponential model and the following parameters were estimated: apparent clearance 180 l h−1; apparent V1 (l) 1450 × (1+0.0013 × dose (mg)), apparent V2 (l) 21 300 × (1–0.0013 × dose (mg)) × (1+2.95 × height (m)) and apparent Q 6950 l h−1. Distribution and elimination half-lives were 0.13 h and 85 h respectively. © 1999 Cancer Research Campaig
- …