Soft System Dynamics Methodology (SSDM): Combining Soft Systems Methodology (SSM) and System Dynamics (SD)

Soft System Dynamics Methodology (SSDM), a systemic methodology product of the combination of two widely used systems-based methodologies from two different systems thinking paradigms, Systems Dynamics (SD) and Soft Systems Methodology (SSM), is presented. The paper argues that by combining some of SD and SSM stages, within the intellectual framework proposed by SSDM, a methodology developed by one of the authors¹ much can be gained in a systemic intervention to tackle complex social problematic situations. A framework for comparing the ontological, epistemological and methodological principles of SD, SSM and SSDM is proposed and the synthesizing and dialectical role of SSDM is advanced. The 10 stages of SSDM are outlined and illustrated by an application on a small Peruvian company; and a set of conclusions and points for further research are discussed.     

Planning of dynamically feasible trajectories for translational, planar, and underconstrained cable-driven robots

Extensively studied since the early nineties, cable-driven robots have attracted the growing interest of the industrial and scientific community due to their desirable and peculiar attributes. In particular, underconstrained and planar cable robots can find application in several fields, and specif- ically, in the packaging industry. The planning of dynamically feasible trajectories （i.e., trajectories along which cable slackness and excessive tensions are avoided） is particularly challenging when dealing with such a topology of cable robots, which rely on gravity to maintain their cables in tension. This paper, after stressing the current relevance of cable robots, presents an extension and a generalization of a model-based method developed to translate typical cable tension bilateral bounds into intuitive limits on the velocity and acceleration of the robot end effector along a prescribed path. Such a new formulation of the method is based on a parametric expression of cable tensions. The computed kine- matic limits can then be incorporated into any trajectory planning algorithm. The method is developed with reference to a hybrid multi-body cable robot topology which can be functionally advantageous but worsen the problem of keeping feasible tensions in the cables both in static and dynamic conditions. The definition of statically feasible workspace is also introduced to identify the positions where static equilibrium can be maintained with feasible tensions. Finally, some aspects related to the practical implementation of the method are discussed.     

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae

Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein-protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein-protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.     

Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice

The mouse ortholog of human FACE-1, Zmpste24, is a multispanning membrane protein widely distributed in mammalian tissues and structurally related to Afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones. Disruption of the gene Zmpste24 caused severe growth retardation and premature death in homozygous-null mice. Histopathological analysis of the mutant mice revealed several abnormalities, including dilated cardiomyopathy, muscular dystrophy and lipodystrophy. These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies. In agreement with this finding, Zmpste24-null mice are defective in the proteolytic processing of prelamin A. This deficiency in prelamin A maturation leads to the generation of abnormalities in nuclear architecture that probably underlie the many phenotypes observed in both mice and humans with mutations in the lamin A gene. These results indicate that prelamin A is a specific substrate for Zmpste24 and demonstrate the usefulness of genetic approaches for identifying the in vivo substrates of proteolytic enzymes.     

Vapour undersaturation in primitive mid-ocean-ridge basalt and the volatile content of Earth's upper mantle

The analysis of volatiles in magmatic systems can be used to constrain the volatile content of the Earth's mantle and the influence that magmatic degassing has on the chemistry of the oceans and the atmosphere. But most volatile elements have very low solubilities in magmas at atmospheric pressure, and therefore virtually all erupted lavas are degassed and do not retain their primary volatile signatures. Here we report the undersaturated pre-eruptive volatile content for a suite of mid-ocean-ridge basalts from the Siqueiros intra-transform spreading centre. The undersaturation leads to correlations between volatiles and refractory trace elements that provide new constraints on volatile abundances and their behaviour in the upper mantle. Our data generate improved limits on the abundances of carbon dioxide, water, fluorine, sulphur and chlorine in the source of normal mid-ocean-ridge basalt. The incompatible behaviour of carbon dioxide, together with the CO(2)/Nb and CO(2)/Cl ratios, permit estimates of primitive carbon dioxide and chlorine to be made for degassed and chlorine-contaminated mid-ocean-ridge basalt magmas, and hence constrain degassing and contamination histories of mid-ocean ridges.     

Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response

Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus.     

Neuroanatomy: brain asymmetry and long-term memory

The asymmetrical positioning of neural structures on the left or right side of the brain in vertebrates and in invertebrates may be correlated with brain laterality, which is associated with cognitive skills. But until now this has not been illustrated experimentally. Here we describe an asymmetrically positioned brain structure in the fruitfly Drosophila and find that the small proportion of wild-type flies that have symmetrical brains with two such structures lack a normal long-term memory, although their short-term memory is intact. Our results indicate that brain asymmetry may be required for generating or retrieving long-term memory.     

Solving the factorization problem with P systems

P systems have been used many times to face with computationally difficult problems, such as NP-complete decision problems and NP-hard optimization problems. In this paper we focus our attention on another computationally intractable problem: factorization. In particular, we first propose a simple method to encode binary numbers using multisets. Then, we describe three families of P systems: the first two allow to add and to multiply two binary encoded numbers, respectively, and the third solves the factorization problem.     

Neurexins and neuroligins: synapses look out of the nervous system

The scientific interest in the family of the so-called nervous vascular parallels has been growing steadily for the past 15 years, either by addition of new members to the group or, lately, by deepening the analysis of established concepts and mediators. Proteins governing both neurons and vascular cells are known to be involved in events such as cell fate determination and migration/guidance but not in the last and apparently most complex step of nervous system development, the formation and maturation of synapses. Hence, the recent addition to this family of the specific synaptic proteins, Neurexin and Neuroligin, is a double innovation. The two proteins, which were thought to be “simple” adhesive links between the pre- and post-synaptic sides of chemical synapses, are in fact extremely complex and modulate the most subtle synaptic activities. We will discuss the relevant data and the intriguing challenge of transferring synaptic activities to vascular functions.     

Isoform specific phosphorylation of p53 by protein kinase CK1

The ability of three isoforms of protein kinase CK1 (α, γ₁, and δ) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide reproducing its 1–28 sequence. Both substrates are readily phosphoylated by CK1δ and CK1α, but not by the γ isoform. Affinity of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K _m 0.82 μM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1 is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and on a remote docking site mapped to the K²²¹RQK²²⁴ loop according to modeling and mutational analysis.