Stable and unstable attractors in Boolean networks

Boolean networks at the critical point have been a matter of debate for many years as, e.g., scaling of number of attractor with system size. Recently it was found that this number scales superpolynomially with system size, contrary to a common earlier expectation of sublinear scaling. We here point to the fact that these results are obtained using deterministic parallel update, where a large fraction of attractors in fact are an artifact of the updating scheme. This limits the significance of these results for biological systems where noise is omnipresent. We here take a fresh look at attractors in Boolean networks with the original motivation of simplified models for biological systems in mind. We test stability of attractors w.r.t. infinitesimal deviations from synchronous update and find that most attractors found under parallel update are artifacts arising from the synchronous clocking mode. The remaining fraction of attractors are stable against fluctuating response delays. For this subset of stable attractors we observe sublinear scaling of the number of attractors with system size.Comment: extended version, additional figur

Phase transition in a class of non-linear random networks

We discuss the complex dynamics of a non-linear random networks model, as a function of the connectivity k between the elements of the network. We show that this class of networks exhibit an order-chaos phase transition for a critical connectivity k = 2. Also, we show that both, pairwise correlation and complexity measures are maximized in dynamically critical networks. These results are in good agreement with the previously reported studies on random Boolean networks and random threshold networks, and show once again that critical networks provide an optimal coordination of diverse behavior.Comment: 9 pages, 3 figures, revised versio

The dynamics of critical Kauffman networks under asynchronous stochastic update

We show that the mean number of attractors in a critical Boolean network under asynchronous stochastic update grows like a power law and that the mean size of the attractors increases as a stretched exponential with the system size. This is in strong contrast to the synchronous case, where the number of attractors grows faster than any power law.Comment: submitted to PR

L’ADAPTATION POSITIVE DES FAMILLES LATINOS AVEC UN ENFANT AYANT UNE DÉFICIENCE INTELLECTUELLE: UNE PREMIÈRE VUE DE LA THÉORIE DE L’ADAPTATION POSITIVE

Historically, research on disability and family dynamics drew from Psychology and Medicine. Consequently, eugenics models, grief theory, and other largely decontextualized frameworks of stress and coping were used to explain families of children with disabilities. This is a report of an initial test of a set of ideas the Singer research team has combined in order to explore the cognitive and problem-solving approaches of families of children with disabilities. Our purpose is to propose a contextualized theory for explaining how cultural diversity has an impact on positive adaptation to a child’s disability. This theory addresses the following: 1) attachment; 2) internal and external cultural resistance to stigmas about disability; and 3) perceived informal (family/friends) and formal (professionals) sources of support for positive views about disability and parenting. Sampling Latino families demonstrated how cultural contexts demonstrate a different flavour from majority culture interpretations of these cognitive terms of our proposed theory. Transcripts of the interviews were coded using grounded theory analysis, specifically, the constant comparative method. We discuss the goodness of fit for themes emerging from the coding process with the proposed theory terms. Results confirm attachment, social supports, and cultural resistance as terms for future development of this proposed theory. Keywords: Disability and parenting, positive adaptation, Latinos and disability, culture and disabilityÀ travers l’histoire, la recherche sur les handicapés et les relations intrafamiliales utilisait comme sources la psychologie et la médicine. Par conséquent, les modèles de l’eugénisme, les théories sur le deuil, et d’autres cadres analytiques sur le stress et les stratégies d’adaptation, plutôt décontextualisés, étaient utilisés afin d’expliquer aux autres comment fonctionnaient les familles avec un enfant handicapé. Ceci est un reportage sur un test initial d’un ensemble d’idées qu’a combiné l’équipe de recherche Singer afin d’aborder les approches cognitives et méthodes actives des familles des enfants handicapés. Nous proposons une théorie contextualisée afin d’expliquer comment la diversité culturelle aurait un effet sur l’adaptation positive de la famille face à l’handicap de leur enfant. Cette théorie aborde les idées suivantes : 1) l’attachement; 2) les résistances culturelles internes et externes aux stigmates sur l’handicap; et 3) les sources d’information sur l’handicap et le parentage liées à l’adaptation positive perçues comme informelles (famille/amis) et formelles (les professionnels). En utilisant un échantillon de familles Latinos, nous démontrons comment les contextes culturels démontrent des interprétations différentes des termes cognitifs de notre théorie, et non l’interprétation de la culture majoritaire. Les transcriptions des interviews étaient codées selon la théorie ancrée, plus spécifiquement la méthode de la comparaison constante. Nous discutons la concordance des thèmes venus via le processus d’encodage avec les termes clés de la nouvelle théorie proposée. Les résultats de cette recherche confirment que l’attachement, le soutien social, et la résistance culturelle seront des termes clés dans le développement de cette théorie proposée. Mots clés : Handicap et parentage, Adaptation positive, Latinos et handicap, culture et handica

Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies

The combination of antagonism at histamine H3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy)benzene)]sulfonylurea exhibited the best H3 antagonism affinity. However, since all these derivatives failed to block KATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype

New quinoxaline derivatives as potential MT₁ and MT₂ receptor ligands.

Ever since the idea arose that melatonin might promote sleep and resynchronize circadian rhythms, many research groups have centered their efforts on obtaining new melatonin receptor ligands whose pharmacophores include an aliphatic chain of variable length united to an N-alkylamide and a methoxy group (or a bioisostere), linked to a central ring. Substitution of the indole ring found in melatonin with a naphthalene or quinoline ring leads to compounds of similar affinity. The next step in this structural approximation is to introduce a quinoxaline ring (a bioisostere of the quinoline and naphthalene rings) as the central nucleus of future melatoninergic ligand

Salivary Metabolomic Signatures and Body Mass Index in Italian Adolescents: A Pilot Study

Context: Obesity surveillance is scarce in adolescents, and little is known on whether salivary metabolomics data, emerging minimally invasive biomarkers, can characterize metabolic patterns associated with overweight or obesity in adolescents. Objective: This pilot study aims to identify the salivary molecular signatures associated with body mass index (BMI) in Italian adolescents. Methods: Saliva samples and BMI were collected in a subset of n = 74 young adolescents enrolled in the Public Health Impact of Metal Exposure study (2007-2014). A total of 217 untargeted metabolites were identified using liquid chromatography-high resolution mass spectrometry. Robust linear regression was used to cross-sectionally determine associations between metabolomic signatures and sex-specific BMI-for-age z-scores (z-BMI). Results: Nearly 35% of the adolescents (median age: 12 years; 51% females) were either obese or overweight. A higher z-BMI was observed in males compared to females (P = .02). One nucleoside (deoxyadenosine) and 2 lipids (18:0-18:2 phosphatidylcholine and dipalmitoyl-phosphoethanolamine) were negatively related to z-BMI (P < .05), whereas 2 benzenoids (3-hydroxyanthranilic acid and a phthalate metabolite) were positively associated with z-BMI (P < .05). In males, several metabolites including deoxyadenosine, as well as deoxycarnitine, hyodeoxycholic acid, N-methylglutamic acid, bisphenol P, and trigonelline were downregulated, while 3 metabolites (3-hydroxyanthranilic acid, theobromine/theophylline/paraxanthine, and alanine) were upregulated in relation to z-BMI (P < .05). In females, deoxyadenosine and dipalmitoyl-phosphoethanolamine were negatively associated with z-BMI while deoxycarnitine and a phthalate metabolite were positively associated (P < .05). A single energy-related pathway was enriched in the identified associations in females (carnitine synthesis, P = .04). Conclusion: Salivary metabolites involved in nucleotide, lipid, and energy metabolism were primarily altered in relation to BMI in adolescents

Substitutions of fluorine atoms and phenoxy groups in the synthesis of quinoxaline 1,4-di-N-oxide derivatives.

The unexpected substitution of fluorine atoms and phenoxy groups attached to quinoxaline or benzofuroxan rings is described. The synthesis of 2-benzyl- and 2-phenoxy- 3-methylquinoxaline 1,4-di-N-oxide derivatives was based on the classical Beirut reaction. The tendency of fluorine atoms linked to quinoxaline or benzofuroxan rings to be replaced by a methoxy group when dissolved in an ammonia saturated solution of methanol was clearly demonstrated. In addition, 2-phenoxyquinoxaline 1,4-di-N-oxide derivatives became 2-aminoquinoxaline 1,4-di-N-oxide derivatives in the presence of gaseous ammonia