Graphic Thinking and Digital Processes: Three Built Case Studies of Digital Materiality

Think strategic link between computer programming; digital modeling; the data; matter and CNC manufacturing in the various stages of the architectural project is key to update our discipline with new technologies. Our proposal to articulate and digital graphic thought processes; developable folded geometries and compositions is rooted in an expanded graphic thinking through multiple conceptual tools that are already part of the operational structure of our discipline

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility

Do theoretical physicists care about the protein-folding problem?

The prediction of the biologically active native conformation of a protein is one of the fundamental challenges of structural biology. This problem remains yet unsolved mainly due to three factors: the partial knowledge of the effective free energy function that governs the folding process, the enormous size of the conformational space of a protein and, finally, the relatively small differences of energy between conformations, in particular, between the native one and the ones that make up the unfolded state. Herein, we recall the importance of taking into account, in a detailed manner, the many interactions involved in the protein folding problem (such as steric volume exclusion, Ramachandran forces, hydrogen bonds, weakly polar interactions, coulombic energy or hydrophobic attraction) and we propose a strategy to effectively construct a free energy function that, including the effects of the solvent, could be numerically tractable. It must be pointed out that, since the internal free energy function that is mainly described does not include the constraints of the native conformation, it could only help to reach the 'molten globule' state. We also discuss about the limits and the lacks from which suffer the simple models that we, physicists, love so much.Comment: 27 pages, 4 figures, LaTeX file, aipproc package. To be published in the book: "Meeting on Fundamental Physics 'Alberto Galindo'", Alvarez-Estrada R. F. et al. (Ed.), Madrid: Aula Documental, 200

Man and Machine: Questions of Risk, Trust and Accountability in Today's AI Technology

Artificial Intelligence began as a field probing some of the most fundamental questions of science - the nature of intelligence and the design of intelligent artifacts. But it has grown into a discipline that is deeply entwined with commerce and society. Today's AI technology, such as expert systems and intelligent assistants, pose some difficult questions of risk, trust and accountability. In this paper, we present these concerns, examining them in the context of historical developments that have shaped the nature and direction of AI research. We also suggest the exploration and further development of two paradigms, human intelligence-machine cooperation, and a sociological view of intelligence, which might help address some of these concerns.Comment: Preprin