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"Packer, Martin J"
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Child development : understanding a cultural perspective
Every child is born into a community, a society with a culture, in which he or she will live, grow, and develop. Cultures lead to differences in children's development, but equally important, culture is an essential component of every child's psychological development. Child Development takes a chronological approach, from prenatal development to adolescence, in which social, cognitive, emotional, and physical aspects of development are interwoven. Author Martin J. Packer integrates cross-cultural examples from different parts of the world to illustrate how culture plays a constitutive role in children's development. This book includes an in-depth discussion of human evolution, the history of language, and the human lifespan, as well as the theoretical perspectives of scientific research on children's development -- Provided by the publisher.
Book
Experimental free ligand conformations: a missing link in structure-based drug discovery
A range of recent structure-based drug discovery case studies demonstrate the power of nuclear magnetic resonance (NMR) conformational analysis to elucidate SAR trends with respect to conformational preferences of the free ligand (4-14). [...]with the advent of high performance computing, a combination of NMR data and theoretical models can be used to rapidly quantify the populations of all accessible conformers of a ligand in a relatively short timeframe. In AstraZeneca, efforts are ongoing to automate and routinely integrate potency and simple proton NMR data with structural information to enhance the structure-based drug design paradigm, with the ultimate intent of accelerating project cycle times. [...]to derive synergy through the combination of x-ray structure and free ligand NMR conformations, and achieve a turnaround compatible with ‘design, make, test, analyze’ cycle times, it is crucial to establish a collaborative culture among the different disciplines involved in drug optimization.
Journal Article
Reflections on the learning sciences
\"This volume offers a historical and critical analysis of the emerging field of the learning sciences, which takes an interdisciplinary approach to understanding and improving how children and adults learn. It features a wide range of authors, including established scholars who founded and guided the learning sciences through the initial turbulence of forming a new line of academic inquiry, as well as newcomers who are continuing to shape the field. This diversity allows for a broad yet selective perspective on what the learning sciences is, why it came to be, and how contributors conduct their work. Reflections on the Learning Sciences serves both as a starting point for discussion among scholars familiar with the discipline and as an introduction for those interested in learning more. It will benefit graduate students and researchers in computer science, educational psychology, instructional technology, science, engineering, and mathematics\"-- Provided by publisher.
Book
Bifocal stance theory, the transmission metaphor, and institutional reality
Biologists have replaced the metaphor of “genetic transmission” with a detailed account of the molecular mechanisms underlying the phenomenon which Darwin referred to as “like produces like.” Cultural evolution theorists, in contrast, continue to appeal to “imitation” or “copying.” The notion of ritual and instrumental stances does not resolve this issue, and ignores the institutions in which people live.
Journal Article
Nuclear magnetic resonance free ligand conformations and atomic resolution dynamics
Knowledge of free ligand conformational preferences (energy minima) and conformational dynamics (rotational energy barriers) of small molecules in solution can guide drug design hypotheses and help rank ideas to bias syntheses towards more active compounds. Visualization of conformational exchange dynamics around torsion angles, by replica exchange with solute tempering molecular dynamics (REST-MD), gives results in agreement with high-resolution 1H nuclear magnetic resonance (NMR) spectra and complements free ligand conformational analyses. Rotational energy barriers around individual bonds are comparable between calculated and experimental values, making the in-silico method relevant to ranking prospective design ideas in drug discovery programs, particularly across a series of analogs. Prioritizing design ideas, based on calculations and analysis of measurements across a series, efficiently guides rational discovery towards the “right molecules” for effective medicines.
Journal Article
Evolution and Ontogenesis
We explore contemporary evolutionary perspectives on children’s psychological development, questioning the view that high-fidelity, inter-individual transmission of information explains the cumulative character of human cultures, and children’s ontogenesis within these cultures. We argue that humans construct an environmental niche that is unique in being composed of institutions, which function to coordinate activity over multiple time scales. Institutions involve not simply customs or conventions but a deontology of future-binding rights, responsibilities, duties, and obligations. The origins of institutions can be traced in hominin evolution to Paleolithic hunter-gatherers, where kinship, the first institution, made possible community support of an extended and demanding form of ontogenesis. Since the human environmental niche is an institutional reality, children today need to acquire the ability to understand and act effectively within institutions. We propose that this ability emerges not as an adaptation solely to past conditions but through differentiation and reintegration of an “extended ontogenetic system” of which the child is a constituent, leading to a quality of self-consciousness on the part of the child that makes possible the ability to live in an institutional reality.
Journal Article
Predicting the relative binding affinity of mineralocorticoid receptor antagonists by density functional methods
In drug discovery, prediction of binding affinity ahead of synthesis to aid compound prioritization is still hampered by the low throughput of the more accurate methods and the lack of general pertinence of one method that fits all systems. Here we show the applicability of a method based on density functional theory using core fragments and a protein model with only the first shell residues surrounding the core, to predict relative binding affinity of a matched series of mineralocorticoid receptor (MR) antagonists. Antagonists of MR are used for treatment of chronic heart failure and hypertension. Marketed MR antagonists, spironolactone and eplerenone, are also believed to be highly efficacious in treatment of chronic kidney disease in diabetes patients, but is contra-indicated due to the increased risk for hyperkalemia. These findings and a significant unmet medical need among patients with chronic kidney disease continues to stimulate efforts in the discovery of new MR antagonist with maintained efficacy but low or no risk for hyperkalemia. Applied on a matched series of MR antagonists the quantum mechanical based method gave an R
2
= 0.76 for the experimental lipophilic ligand efficiency versus relative predicted binding affinity calculated with the M06-2X functional in gas phase and an R
2
= 0.64 for experimental binding affinity versus relative predicted binding affinity calculated with the M06-2X functional including an implicit solvation model. The quantum mechanical approach using core fragments was compared to free energy perturbation calculations using the full sized compound structures.
Graphical Abstract
Journal Article
Interculturality or Government of Childhood? Challenges of Indigenous Child Care in Colombia
A global phenomenon is the reorganization of care for very young children. Institutions are replacing the context of family and community. Increasingly in Colombia young children spend hours each day in institutions directed by public policy and administrative guidelines. We explore, first, how research on this phenomenon adopts a reductionist perspective, a focus on “quality” and “outcomes” measured in ways that assume a Western axiology. Second, we consider how the institutionalization of childhood amounts to a “government” that imposes Western individualism. Third, we illustrate the tension created for childcare professionals and for Indigenous communities as their rights to make decisions about the best ways to care for children are threatened.
Journal Article
Use of quantitative (1)H NMR chemical shift changes for ligand docking into barnase
(1)H NMR complexation-induced changes in chemical shift (CIS) of HN protons have been used to characterize the complexes of barnase with the deoxyoligonucleotides d(GC) and d(CGAC). Quantitative shift changes are used not only to locate the most probable binding site (using ring-current shifts), but also to determine the orientation of the ligand within the binding site, based on a more complete shift calculation including bond magnetic anisotropies and electric field effects. For both ligands, the guanine is in the same binding site cleft, in the same position as identified in the crystal structure of the d(CGAC) complex. By contrast, a previous X-ray crystal structure of the d(GC) complex showed the ligand in the mouth of the active site, rather than at the guanyl-specific site, implying that the location may be an artifact of the crystallisation process.
Journal Article