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We prove a central limit theorem for the components of the largest eigenvectors of the adjacency matrix of a finite-dimensional random dot product graph whose true latent positions are unknown. We use the spectral embedding of the adjacency matrix to construct consistent estimates for the latent positions, and we show that the appropriately scaled differences between the estimated and true latent positions converge to a mixture of Gaussian random variables. We state several corollaries, including an alternate proof of a central limit theorem for the first eigenvector of the adjacency matrix of an Erdos-Rényi random graph.

In contrast with crystallization, there is no noticeable structural change at the glass transition. Characteristic features of glassy dynamics that appear below an onset temperature, T0(refs ,,), are qualitatively captured by mean field theory, which assumes uniform local structure. Studies of more realistic systems have found only weak correlations between structure and dynamics. This raises the question: is structure important to glassy dynamics in three dimensions? We answer this question affirmatively, using machine learning to identify a new field, ‘softness’ which characterizes local structure and is strongly correlated with dynamics. We find that the onset of glassy dynamics at T0corresponds to the onset of correlations between softness (that is, structure) and dynamics. Moreover, we construct a simple model of relaxation that agrees well with our simulation results, showing that a theory of the evolution of softness in time would constitute a theory of glassy dynamics.

The Dishevelled (Dvl) gene family encodes cytoplasmic proteins that are necessary for Wnt signal transduction. Utilizing the yeast two-hybrid system, we identified protein phosphatase 2Calpha (PP2C) as a Dvl-PDZ domain-interacting protein. PP2C exists in a complex with Dvl, beta-catenin, and Axin, a negative regulator of Wnt signaling. In a Wnt-responsive LEF-1 reporter gene assay, expression of PP2C activates transcription and also elicits a synergistic response with beta-catenin and Wnt-1. In addition, PP2C expression relieves Axin-mediated repression of LEF-1-dependent transcription. PP2C utilizes Axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that PP2C is a positive regulator of Wnt signal transduction and mediates its effects through the dephosphorylation of Axin.

Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)/LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK). The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rac1, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rac1 could not inhibit Dvl-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.

We have demonstrated previously that noncoding sequences of genes are a robust source of polymorphisms between mouse species when tested using single-strand conformation polymorphism (SSCP) analysis, and that these polymorphisms are useful for genetic mapping. In this report we demonstrate that presumptive 3'-untranslated region sequence obtained from expressed sequence tags (ESTs) can be analyzed in a similar fashion, and we have used this approach to map 262 loci using an interspecific backcross. These results demonstrate SSCP analysis of genes or ESTs is a simple and efficient means for the genetic localization of transcribed sequences, and is furthermore an approach that is applicable to any system for which there is sufficient sequence polymorphism.

A fullgraph on nvertices, as defined by Fulkerson, is a representation of the intersection and containment relations among a system of nsets. It has an undirected edge between vertices representing intersecting sets and a directed edge from ato bif the corresponding set Acontains B;. Kleitman, Lasaga, and Cowen gave a unified argument to show that asymptotically, almost all full graphs can be obtained by taking an arbitrary undirected graph on the nvertices, distinguishing a clique in this graph, which need not be maximal, and then adding directed edges going out from each vertex in the clique to all vertices to which there is not already an existing undirected edge. Call graphs of this type members of the dominant class. This article obtains the first upper and lower bounds on how large n has to be, so that the asymptotic behavior is indeed observed. It is shown that when n> 170, the dominant class predominates, while when n< 17, the full graphs in the dominant class compose less than half of the total number of realizable full graphs on nvertices.

Actin, the major protein of Naegleria gruberi, is selectively not synthesized during the differentiation of amebae to flagellates. When RNA extracted from cells at intervals during differentiation is translated in the wheat germ cell-free system, a major translation product with the electrophoretic mobility of actin is seen to disappear with time during differentiation. This translation product is shown to be actin by its electrophoretic mobility, copolymerization with rabbit actin, peptide map, and immunoprecipitation by antibodies specific to Naegleria actin. Multiple isoforms of actin are synthesized in the cell-free system. Quantitative immunoprecipitation of translation products was employed to measure the relative amount of actin mRNA. Translatable actin mRNA begins to decrease in abundance within 7 min after the initiation of differentiation and thereafter decreases with a half-life of about 25 min. The selective disappearance of this major translatable mRNA provides a favorable opportunity to dissect the rules governing the half-life of a specific mRNA.

Actin from amebae of Naegleria gruberi has been purified to homogeneity. The purified actin shares many attributes with numerous other actins that have been characterized, including molecular weight, strong binding to DEAE-cellulose, binding to DNase I, reversible polymerization to F-actin, binding of rabbit myosin subfragment 1 to give distinctive arrowheads , formation of Mg paracrystals, and activation of myosin Mg2+-ATPase. In two respects the attributes of Naegleria actin are unusual. Isoelectric focusing resolves three distinct isoforms of the actin, which raises questions about the function of multiple isoforms in a unicellular eukaryote. The amino acid composition closely resembles other actins except that Naegleria actin lacks N tau-methylhistidine. This result indicates that N tau-methylhistidine is not a prerequisite for actin-actin or actin-myosin interactions.

A series of experiments were conducted to identify the factors that could aid passengers in remaining seated during an emergency deceleration of an automated transit system. Sixty subjects, representative of three anthropometric levels, underwent various levels of deceleration in an instrumented vehicle controlled by an automated braking system. The independent variables examined were seat orientation and tilt, seat contour and covering, footrests and armrests, and rate of change of deceleration (jerk). The primary dependent variables were the deceleration levels at which subjects moved from sensors that were imbedded in the experimental seat. Movies were taken and subject comfort ratings were also obtained.The major results indicated that forward-facing subjects sustained higher deceleration levels without being dislodged than subjects sitting at small orientation angles of 15° and 30°. A foot-rest contributed to greater retention of forward-facing subjects as did a seat tilt of 12° back. The maximum deceleration level for retention of 84 percent of the forward-facing passengers sitting on a seat tilted back 12° and using a footrest was 0.36 g.Jerk was found not to be a factor in dislodging subjects during the onset of the emergency stop. It was, however, a factor in the perception of comfort. Subjects reported being more uncomfortable at higher jerk levels. Providing a warning to the passengers of an impending stop may aid them in sustaining higher deceleration levels.

We have utilized a PCR-based analysis of single-strand conformation polymorphisms to identify polymorphisms that can be used for mapping cloned DNA sequences in the mouse. We have found that single-strand conformation polymorphism analysis of sequences that are potentially less subject to conservation (i.e., intron and 3' untranslated regions) is a relatively efficient means of detecting polymorphisms between inbred strains. Fifty percent of the tested primer pairs were polymorphic between inbred strains and 90% were polymorphic between mouse species, which is a frequency comparable to that found for microsatellite repeat sequences. We have found that this technique can be readily used to determine the strain distribution pattern in a recombinant inbred series and is a simple and rapid means to obtain a map position for cloned sequences. When this strategy was tested on a number of previously mapped cloned genes, the strain distribution patterns obtained were consistent with that to be expected on the basis of the known map position. We also tested the utility of this approach for characterizing genes that have not been previously mapped. Dvl, the mouse homolog of the putative Drosophila dishevelled gene, and Adfp, encoding an adipocyte differentiation-related protein, were found to map to chromosome 4. These results were confirmed using single-strand conformation polymorphism analysis of an interspecific backcross.

We have achieved high-efficiency uptake and expression of foreign DNA in mouse Ltk- cells by modifying the DEAE-dextran-mediated transfection method of McCutchan and Pagano (J. Natl. Cancer Inst. 42:351-357, 1968) to include an initial incubation at elevated pH followed by a shock treatment with dimethyl sulfoxide. Up to 80% of mouse Ltk- cells transfected with the herpes simplex virus thymidine kinase gene expressed thymidine kinase as measured by autoradiography.

Étude des données poolées de 2 études comparatives de phase 3 de BOTOX®versus placebo : analyse de l’efficacité sur l’incontinence urinaire et la qualité de vie selon l’état d’infection urinaire ou la nécessité d’autosondage (AS).

Here we present the final results from an extension study assessing long-term onabotulinumtoxinA treatment (3.5 years) in patients with idiopathic overactive bladder.

Looks at the case of Ryan White, a student who is infected with the AIDS virus. His legal fight for the right to attend public school.