Computational structures for design democratization

Thesis (S.M. in Architecture Studies)--Massachusetts Institute of Technology, Dept. of Architecture, June 2012."June 2012." Cataloged from PDF version of thesis.Includes bibliographical references (p. 107-112).The vision to engage non-architects in the design of their habitat through the mediation of computer aids, dates back to the early computational era (1960s-1970s) and is currently being recast under cyber-cultural and technological influences. The computational tools enabling this architectural do-it-yourself-ism have been traditionally conceptualized as mediating "infrastructures:" neutral and non-defining control systems, which ensure the validity of the designs produced by the non-expert users without distorting their personal hypotheses. Through a critical comparative analysis of two basal computational systems for design "democratization," as discussed in Yona Friedman's and Nicholas Negroponte's early 1970s writings, this thesis illustrates that the "infrastructure" metaphor was engendered and still resides in a positivist paradigm of design, allowing for little freedom or intuition on behalf of the user. Rather than denouncing the internal contradictions of the "structure for freedom" model, this thesis inquires into the computational structures of Friedman's and Negroponte's proto-computational proposals in order to identify and critique the assumptions which underpin their optimism about the non-paternalistic character of their control systems. By exposing the discursive role of the internal workings of the two systems in their authors' arguments, along with their cultural and historical biases, this research aims to problematize inherited approaches to computational tools for user empowerment in design which persist until the present, and to hint to new programmatic agendas.by Theodora Vardouli.S.M.in Architecture Studie

Erk5 is a mediator to TGFβ1-induced loss of phenotype and function in human podocytes.

Background: Podocytes are highly specialized cells integral to the normal functioning kidney, however, in diabetic nephropathy injury occurs leading to a compromised phenotype and podocyte dysfunction which critically produces podocyte loss with subsequent renal impairment. TGFβ1 holds a major role in the development of diabetic nephropathy. Erk5 is an atypical mitogen-activated protein (MAP) kinase involved in pathways modulating cell survival, proliferation, differentiation, and motility. Accordingly, the role of Erk5 in mediating TGFβ1-induced podocyte damage was investigated. Methods: Conditionally immortalized human podocytes were stimulated with TGFβ1 (2.5 ng/ml); inhibition of Erk5 activation was conducted with the chemical inhibitor BIX02188 (10 μM) directed to the upstream Mek5; inhibition of Alk5 was performed with SB431542 (10 μM); Ras signaling was inhibited with farnesylthiosalicylic acid (10 μM). Intracellular signaling proteins were investigated by western blotting; phenotype was explored by immunofluorescence; proliferation was assessed with a MTS assay; motility was examined with a scratch assay; barrier function was studied using electric cell-substrate impedance sensing; apoptosis was studied with annexin V-FITC flow cytometry. Results: Podocytes expressed Erk5 which was phosphorylated by TGFβ1 via Mek5, whilst not involving Ras. TGFβ1 altered podocyte phenotype by decreasing P-cadherin staining and increasing α-SMA, as well as reducing podocyte barrier function; both were prevented by inhibiting Erk5 phosphorylation with BIX02188. TGFβ1-induced podocyte proliferation was prevented by BIX02188, whereas the induced apoptosis was not. Podocyte motility was reduced by BIX02188 alone and further diminished with TGFβ1 co-incubation. Conclusion: These results describe for the first time the expression of Erk5 in podocytes and identify it as a potential target for the treatment of diabetic renal disease

L’architecture à l’heure du numérique, des algorithmes au projet

Il y a vingt-cinq ans, l’architecture était encore largement produite à la main, à l’aide d’encre appliquée sur du calque. La diffusion des outils numériques est venue bouleverser la situation. L’écrasante majorité des projets est aujourd’hui conçue au moyen de l’ordinateur. Les outils, on le sait, orientent les pratiques créatives et sont même susceptibles de provoquer leur redéfinition. Quel a été l’impact du numérique sur l’architecture ? Les contributions à cette discussion tentent d’appo..

The death domain kinase RIP1 links the immunoregulatory CD40 receptor to apoptotic signaling in carcinomas

RIP1 is a component of a TRAF2 complex, required for caspase-8 activation and tumor cell killing in response to ligand binding of CD40

ROCK1 and LIMK2 Interact in Spread but Not Blebbing Cancer Cells

Cancer cells migrating within a 3D microenvironment are able to adopt either a mesenchymal or amoeboid mode of migration. Amoeboid migration is characterised by membrane blebbing that is dependent on the Rho effectors, ROCK1/2. We identify LIMK2 as the preferred substrate for ROCK1 but find that LIMK2 did not induce membrane blebbing, suggesting that a LIMK2 pathway is not involved in amoeboid-mode migration. In support of this hypothesis, novel FRET data demonstrate a direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells. Our results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration

A redox state-dictated signalling pathway deciphers the malignant cell specificity of CD40-mediated apoptosis

CD40, a member of the tumour necrosis factor receptor (TNFR) superfamily, has the capacity to cause extensive apoptosis in carcinoma cells, while sparing normal epithelial cells. Yet, apoptosis is only achieved by membrane-presented CD40 ligand (mCD40L), as soluble receptor agonists are but weakly pro-apoptotic. Here, for the first time we have identified the precise signalling cascade underpinning mCD40L-mediated death as involving sequential TRAF3 stabilisation, ASK1 phosphorylation, MKK4 (but not MKK7) activation and JNK/AP-1 induction, leading to a Bak- and Bax-dependent mitochondrial apoptosis pathway. TRAF3 is central in the activation of the NADPH oxidase (Nox)-2 component p40phox and the elevation of reactive oxygen species (ROS) is essential in apoptosis. Strikingly, CD40 activation resulted in down-regulation of Thioredoxin (Trx)-1 to permit ASK1 activation and apoptosis. Although soluble receptor agonist alone could not induce death, combinatorial treatment incorporating soluble CD40 agonist and pharmacological inhibition of Trx-1 was functionally equivalent to the signal triggered by mCD40L. Finally, we demonstrate using normal, ‘para-malignant’ and tumour-derived cells that progression to malignant transformation is associated with increase in oxidative stress in epithelial cells, which coincides with increased susceptibility to CD40 killing, while in normal cells CD40 signalling is cytoprotective. Our studies have revealed the molecular nature of the tumour specificity of CD40 signalling and explained the differences in pro-apoptotic potential between soluble and membrane-bound CD40 agonists. Equally importantly, by exploiting a unique epithelial culture system that allowed us to monitor alterations in the redox-state of epithelial cells at different stages of malignant transformation, our study reveals how pro-apoptotic signals can elevate ROS past a previously hypothesised ‘lethal pro-apoptotic threshold’ to induce death; an observation that is both of fundamental importance and carries implications for cancer therap

Mutations in Protein-Binding Hot-Spots on the Hub Protein Smad3 Differentially Affect Its Protein Interactions and Smad3-Regulated Gene Expression

Hub proteins are connected through binding interactions to many other proteins. Smad3, a mediator of signal transduction induced by transforming growth factor beta (TGF-β), serves as a hub protein for over 50 protein-protein interactions. Different cellular responses mediated by Smad3 are the product of cell-type and context dependent Smad3-nucleated protein complexes acting in concert. Our hypothesis is that perturbation of this spectrum of protein complexes by mutation of single protein-binding hot-spots on Smad3 will have distinct consequences on Smad3-mediated responses.We mutated 28 amino acids on the surface of the Smad3 MH2 domain and identified 22 Smad3 variants with reduced binding to subsets of 17 Smad3-binding proteins including Smad4, SARA, Ski, Smurf2 and SIP1. Mutations defective in binding to Smad4, e.g., D408H, or defective in nucleocytoplasmic shuttling, e.g., W406A, were compromised in modulating the expression levels of a Smad3-dependent reporter gene or six endogenous Smad3-responsive genes: Mmp9, IL11, Tnfaip6, Fermt1, Olfm2 and Wnt11. However, the Smad3 mutants Y226A, Y297A, W326A, K341A, and E267A had distinct differences on TGF-β signaling. For example, K341A and Y226A both reduced the Smad3-mediated activation of the reporter gene by ∼50% but K341A only reduced the TGF-β inducibilty of Olfm2 in contrast to Y226A which reduced the TGF-β inducibility of all six endogenous genes as severely as the W406A mutation. E267A had increased protein binding but reduced TGF-β inducibility because it caused higher basal levels of expression. Y297A had increased TGF-β inducibility because it caused lower Smad3-induced basal levels of gene expression.Mutations in protein binding hot-spots on Smad3 reduced the binding to different subsets of interacting proteins and caused a range of quantitative changes in the expression of genes induced by Smad3. This approach should be useful for unraveling which Smad3 protein complexes are critical for specific biological responses

Performed by and Performative for

In this paper I identify the “infrastructure model” as the predominant approach to computationally mediated participatory design from the 1960s until the present, and discuss its history, conceptual underpinnings, and limitations. As case studies for this analysis, I use the French-based architect Yona Friedman’s and the MIT Architecture Machine Group’s 1970s proposals for participatory design computational systems. I employ the polysemic notion of “performance” to interrogate the two systems in three levels: What rationale supports the authors’ claims that in order for design to well perform for its future users, it should be performed by them? What computational models are developed to enable users to perform their own designs? How can performance, as an intuitive, improvisational process, be used to criticize the traditional models of computation in design participation and devise new computational agendas