Antichaos in a Class of Random Boolean Cellular Automata

A variant of Kauffman's model of cellular metabolism is presented. It is a randomly generated network of boolean gates, identical to Kauffman's except for a small bias in favor of boolean gates that depend on at most one input. The bias is asymptotic to 0 as the number of gates increases. Upper bounds on the time until the network reaches a state cycle and the size of the state cycle, as functions of the number of gates $n$, are derived. If the bias approaches 0 slowly enough, the state cycles will be smaller than $n^c$ for some $c<1$. This lends support to Kauffman's claim that in his version of random network the average size of the state cycles is approximately $n^{1/2}$.Comment: 12 pages. A uuencoded, tar-compressed postscipt file containing figures has been adde

Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status

Biological parameters influencing the response of human colorectal cancers (CRCs) to CPT-11, a topoisomerase 1 (top1) inhibitor, were investigated using a panel of nine CRCs xenografted into nude mice. CRC xenografts differed in their p53 status (wt or mut) and in their microsatellite instability phenotype (MSI+when altered). Five CRC xenografts were established from clinical samples. All five had a functional p53, two were MSI+and three were MSI–. Tumour-bearing nude mice were treated intraperitonealy (i.p.) with CPT-11. At 10 mg kg–1of CPT-11, four injections at 4-day intervals, four of the five xenografts responded to CPT-11 (growth delay of up to 10 days); the non-responder tumour was MSI−. At 40 mg kg−1of CPT-11, six injections at 4-day intervals, the five CRCs displayed variable but marked responses with complete regressions. In order to assess the role of p53 status in CPT-11 response, four CRC lines were used. HT29 cell line was MSI−/ Ala273-mutp53, its subclone HT29A3 being transfected by wtp53. LoVo cell line was MSI+/ wtp53, its subclone X17LoVo dominantly expressed Ala273-mutp53 after transfection. LoVo tumours (MSI+/ mutp53) were more sensitive than X17LoVo (MSI+/ mutp53. HT 29 tumours (MSI−Imutp53), were refractory to CPT-11 while HT29A3 tumours (MSI−/ wtp53) were sensitive, showing that wtp53 improves the drug-response in these MSI−tumours. Levels of mRNA expression of top1, fasR, TP53 and mdr1 were semi-quantified by reverse transcription polymerase chain reaction. None of these parameters correlated with CPT-11 response. Taken together, these observations indicate that MSI and p53 alterations could be associated with different CPT-11 sensitivities; MSI phenotype moderately influences the CPT-11 sensitivity, MSI+being more sensitive than MSI−CRC freshly obtained from patients, mutp53 status being associated with a poor response to CPT-11. © 2000 Cancer Research Campaig

Stress transmission in wet granular materials

We analyze stress transmission in wet granular media in the pendular state by means of three-dimensional molecular dynamics simulations. We show that the tensile action of capillary bonds induces a self-stressed particle network organized in two percolating "phases" of positive and negative particle pressures. Various statistical descriptors of the microstructure and bond force network are used to characterize this partition. Two basic properties emerge: 1) The highest particle pressure is located in the bulk of each phase; 2) The lowest pressure level occurs at the interface between the two phases, involving also the largest connectivity of the particles via tensile and compressive bonds. When a confining pressure is applied, the number of tensile bonds falls off and the negative phase breaks into aggregates and isolated sites

Quasiprojectile breakup and isospin equilibration at Fermi energies: an indication of longer projectile-target contact times?

An investigation of the quasiprojectile breakup channel in semiperipheral and peripheral collisions of $^{58,64}$Ni+$^{58,64}$Ni at 32 and 52 MeV/nucleon is presented. Data have been acquired in the first experimental campaign of the INDRA-FAZIA apparatus in GANIL. The effect of isospin diffusion between projectile and target in the two asymmetric reactions has been highlighted by means of the isospin transport ratio technique, exploiting the neutron-to-proton ratio of the quasiprojectile reconstructed from the two breakup fragments. We found evidence that, for the same reaction centrality, a higher degree of relaxation of the initial isospin imbalance is achieved in the breakup channel with respect to the more populated binary output, possibly indicating the indirect selection of specific dynamical features. We have proposed an interpretation based on different average projectile-target contact times related to the two exit channels under investigation, with a longer interaction for the breakup channel. The time information has been extracted from AMD simulations of the studied systems coupled to GEMINI++: the model calculations support the hypothesis hereby presented

Analysis of the Plant bos1 Mutant Highlights Necrosis as an Efficient Defence Mechanism during D. dadantii/Arabidospis thaliana Interaction

Dickeya dadantii is a broad host range phytopathogenic bacterium provoking soft rot disease on many plants including Arabidopsis. We showed that, after D. dadantii infection, the expression of the Arabidopsis BOS1 gene was specifically induced by the production of the bacterial PelB/C pectinases able to degrade pectin. This prompted us to analyze the interaction between the bos1 mutant and D. dadantii. The phenotype of the infected bos1 mutant is complex. Indeed, maceration symptoms occurred more rapidly in the bos1 mutant than in the wild type parent but at a later stage of infection, a necrosis developed around the inoculation site that provoked a halt in the progression of the maceration. This necrosis became systemic and spread throughout the whole plant, a phenotype reminiscent of that observed in some lesion mimic mutants. In accordance with the progression of maceration symptoms, bacterial population began to grow more rapidly in the bos1 mutant than in the wild type plant but, when necrosis appeared in the bos1 mutant, a reduction in bacterial population was observed. From the plant side, this complex interaction between D. dadantii and its host includes an early plant defence response that comprises reactive oxygen species (ROS) production accompanied by the reinforcement of the plant cell wall by protein cross-linking. At later timepoints, another plant defence is raised by the death of the plant cells surrounding the inoculation site. This plant cell death appears to constitute an efficient defence mechanism induced by D. dadantii during Arabidopsis infection

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Harnessing collective intelligence for the future of learning – a co-constructed research and development agenda

Learning, defined as the process of constructing meaning and developing competencies to act on it, is instrumental in helping individuals, communities, and organizations tackle challenges. When these challenges increase in complexity and require domain knowledge from diverse areas of expertise, it becomes difficult for single individuals to address them. In this context, collective intelligence, a capacity of groups of people to act together and solve problems using their collective knowledge, becomes of great importance. Technologies are instrumental both to support and understand learning and collective intelligence, hence the need for innovations in the area of technologies that can support user needs to learn and tackle collective challenges. Use-inspired research is a fitting paradigm that spans applied solutions and scientific explanations of the processes of learning and collective intelligence, and that can improve the technologies that may support them. Although some conceptual and theoretical work explaining and linking learning with collective intelligence is emerging, technological infrastructures as well as methodologies that employ and evidence that support them are nascent. We convened a group of experts to create a middleground and engage with the priorities for use-inspired research. Here we detail directions and methods they put forward as most promising for advancing a scientific agenda around learning and collective intelligence