Biomedical subjects

S Boettcher

Publications and source records attributed to S Boettcher.

18 recordsLinked to original sources

PubMed2001

Argonaute2, a link between genetic and biochemical analyses of RNAi.

Double-stranded RNA induces potent and specific gene silencing through a process referred to as RNA interference (RNAi) or posttranscriptional gene silencing (PTGS). RNAi is mediated by RNA-induced silencing complex (RISC), a sequence-specific, multicomponent nuclease that destroys messenger RNAs homologous to the silencing trigger. RISC is known to contain short RNAs ( approximately 22 nucleotides) derived from the double-stranded RNA trigger, but the protein components of this activity are unknown. Here, we report the biochemical purification of the RNAi effector nuclease from cultured Drosophila cells. The active fraction contains a ribonucleoprotein complex of approximately 500 kilodaltons. Protein microsequencing reveals that one constituent of this complex is a member of the Argonaute family of proteins, which are essential for gene silencing in Caenorhabditis elegans, Neurospora, and Arabidopsis. This observation begins the process of forging links between genetic analysis of RNAi from diverse organisms and the biochemical model of RNAi that is emerging from Drosophila in vitro systems.

Amino Acid Sequence↗

PubMed2001

Extremal optimization for graph partitioning.

Extremal optimization is a new general-purpose method for approximating solutions to hard optimization problems. We study the method in detail by way of the computationally hard (NP-hard) graph partitioning problem. We discuss the scaling behavior of extremal optimization, focusing on the convergence of the average run as a function of run time and system size. The method has a single free parameter, which we determine numerically and justify using a simple argument. On random graphs, our numerical results demonstrate that extremal optimization maintains consistent accuracy for increasing system sizes, with an approximation error decreasing over run time roughly as a power law t(-0.4). On geometrically structured graphs, the scaling of results from the average run suggests that these are far from optimal with large fluctuations between individual trials. But when only the best runs are considered, results consistent with theoretical arguments are recovered.

Journal Article↗

PubMed2001

Optimization with extremal dynamics.

We explore a new general-purpose heuristic for finding high-quality solutions to hard discrete optimization problems. The method, called extremal optimization, is inspired by self-organized criticality, a concept introduced to describe emergent complexity in physical systems. Extremal optimization successively updates extremely undesirable variables of a single suboptimal solution, assigning them new, random values. Large fluctuations ensue, efficiently exploring many local optima. We use extremal optimization to elucidate the phase transition in the 3-coloring problem, and we provide independent confirmation of previously reported extrapolations for the ground-state energy of +/-J spin glasses in d = 3 and 4.

Journal Article↗

PubMed2001

Ventilation-induced chemokine and cytokine release is associated with activation of nuclear factor-kappaB and is blocked by steroids.

Recent clinical trials have shown that the survival of patients with acute respiratory distress syndrome (ARDS) is improved by ventilation with reduced volumes. These studies suggested that overinflation of the lungs causes overactivation of the immune system. The present study investigated the hypothesis that ventilation with increased tidal volumes results in early responses similar to those caused by stimulation with one of the major risk factors for ARDS: bacterial lipopolysaccharide (LPS). We therefore compared the effects of ventilation (-10 cm H2O or -25 cm H2O end-inspiratory pressure) and LPS (50 microg/ml) on nuclear factor (NF)-kappaB activation, chemokine release, and cytokine release in isolated perfused lungs obtained from BALB/C mice. We found that both LPS and ventilation with -25 cm H2O (overventilation; OV) caused translocation of NF-kappaB, which was abolished by pretreatment with the steroid dexamethasone. Furthermore, both treatments resulted in similar increases in perfusate levels of alpha-chemokines (macrophage inflammatory protein; [MIP]-2; KC), beta-chemokines (macrophage chemotactic protein-1; MIP-1alpha), and cytokines (tumor necrosis factor-alpha, interleukin-6), which were largely prevented by dexamethasone pretreatment. In LPS-resistant C3H/HeJ mice, only OV, and not LPS, caused translocation of NF-kappaB and release of MIP-2. We conclude that OV evokes early inflammatory responses similar to those evoked by LPS (i.e., NF-kappaB translocation and release of proinflammatory mediators). The NF-kappaB translocation elicited by OV appears to be independent of Toll-like receptor 4 and not due to LPS contamination introduced by the ventilator. Our data further suggest that steroids might be considered as a subsidiary treatment during artificial mechanical ventilation.

Animals↗

PubMed2000

dc = 4 is the upper critical dimension for the Bak-Sneppen model.

Numerical results are presented indicating d(c) = 4 as the upper critical dimension for the Bak-Sneppen evolution model. This finding agrees with previous theoretical arguments, but contradicts a recent Letter [Phys. Rev. Lett. 80, 5746 (1998)] that placed d(c) as high as d = 8. In particular, we find that avalanches are compact for all dimensions d< or =4 and are fractal for d>4. Under those conditions, scaling arguments predict a d(c) = 4, where hyperscaling relations hold for d< or =4. Other properties of avalanches, studied for 1< or =d< or =6, corroborate this result. To this end, an improved numerical algorithm is presented that is based on the equivalent branching process.

Algorithms↗

PubMed1996