Star Architecture as Socio-Material Assemblage

Taking inspiration from new materialism and assemblage, the chapter deals with star architects and iconic buildings as socio-material network effects that do not pre-exist action, but are enacted in practice, in the materiality of design crafting and city building. Star architects are here conceptualized as part of broader assemblages of actors and practices ‘making star architecture’ a reality, and the buildings they design are considered not just as unique and iconic objects, but dis-articulated as complex crafts mobilizing skills, technologies, materials, and forms of knowledge not necessarily ascribable to architecture. Overcoming narrow criticism focusing on the symbolic order of icons as unique creations and alienated repetitions of capitalist development, the chapter’s main aim is to widen the scope of critique by bridging culture and economy, symbolism and practicality, making star architecture available to a broad, fragmented arena of (potential) critics, unevenly equipped with critical tools and differentiated experiences

Discovery of High-Affinity Protein Binding Ligands – Backwards

BACKGROUND: There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. CONCLUSIONS/SIGNIFICANCE: This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach

Improving benchmarking by using an explicit framework for the development of composite indicators: an example using pediatric quality of care

<p>Abstract</p> <p>Background</p> <p>The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.</p> <p>Objective</p> <p>To present a conceptual framework to develop comprehensive, robust, and transparent composite indicators of pediatric care quality, and to highlight aspects specific to quality measurement in children.</p> <p>Methods</p> <p>We reviewed the scientific literature on composite indicator development, health systems, and quality measurement in the pediatric healthcare setting. Frameworks were selected for explicitness and applicability to a hospital-based measurement system.</p> <p>Results</p> <p>We synthesized various frameworks into a comprehensive model for the development of composite indicators of quality of care. Among its key premises, the model proposes identifying structural, process, and outcome metrics for each of the Institute of Medicine's six domains of quality (safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity) and presents a step-by-step framework for embedding the quality of care measurement model into composite indicator development.</p> <p>Conclusions</p> <p>The framework presented offers researchers an explicit path to composite indicator development. Without a scientifically robust and comprehensive approach to measurement of the quality of healthcare, performance measurement will ultimately fail to achieve its quality improvement goals.</p

A Multigenerational View of Inequality

The study of intergenerational mobility and most population research are governed by a two-generation (parent-to-offspring) view of intergenerational influence, to the neglect of the effects of grandparents and other ancestors and nonresident contemporary kin. While appropriate for some populations in some periods, this perspective may omit important sources of intergenerational continuity of family-based social inequality. Social institutions, which transcend individual lives, help support multigenerational influence, particularly at the extreme top and bottom of the social hierarchy, but to some extent in the middle as well. Multigenerational influence also works through demographic processes because families influence subsequent generations through differential fertility and survival, migration, and marriage patterns, as well as through direct transmission of socioeconomic rewards, statuses, and positions. Future research should attend more closely to multigenerational effects; to the tandem nature of demographic and socioeconomic reproduction; and to data, measures, and models that transcend coresident nuclear families

Characterization of inhibitory effects of NH 2 OH and its N-methyl derivatives on the O 2 -evolving complex of Photosystem II

Inorganic cofactors (Mn, Ca 2+ and Cl - ) are essential for oxidation of H 2 O to O 2 by Photosystem II. The Mn reductants NH 2 OH and its N-methyl derivatives have been employed as probes to further examine the interactions between these species and Mn at the active site of H 2 O oxidation. Results of these studies show that the size of a hydroxylamine derivative regulates its ability to inactivate O 2 evolution activity, and that this size-dependent inhibition behavior arises from the protein structure of Photosystem II. A set of anions (Cl - , F - and SO 4 2- ) is able to slow NH 2 OH and CH 3 NHOH inactivation of intact Photosystem II membranes by exerting a stabilizing influence on the extrinsic 23 and 17 kDa polypeptides. In contrast to this non-specific anion effect, only Cl - is capable of attenuating CH 3 NHOH and (CH 3 ) 2 NOH inhibition in salt-washed preparations lacking the 23 and 17 kDa polypeptides. However, Cl - fails to protect against NH 2 OH inhibition in salt-washed membranes. These results indicate that the attack by NH 2 OH and its N-methyl derivatives on Mn occurs at different sites in the O 2 -evolving complex. The small reductant NH 2 OH acts at a Cl - -insensitive site whereas the inhibitions by CH 3 NHOH and (CH 3 ) 2 NOH involve a site that is Cl - sensitive. These findings are consistent with earlier studies showing that the size of primary amines controls the Cl - sensitivity of their binding to Mn in the O 2 -evolving complex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43537/1/11120_2004_Article_BF00046773.pd

The Many Flavors of Hyperhomocyst(e)inemia: Insights from Transgenic and Inhibitor-Based Mouse Models of Disrupted One-Carbon Metabolism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63367/1/ars.2007.1795.lowlink.pdf_v03.pd