Designing protein β-sheet surfaces by Z-score optimization

Studies of lattice models of proteins have suggested that the appropriate energy expression for protein design may include nonthermodynamic terms to accommodate negative design concerns. One method, developed in lattice model studies, maximizes a quantity known as the "Z-score," which compares the lowest energy sequence whose ground state structure is the target structure to an ensemble of random sequences. Here we show that, in certain circumstances, the technique can be applied to real proteins. The resulting energy expression is used to design the β-sheet surfaces of two real proteins. We find experimentally that the designed proteins are stable and well folded, and in one case is even more thermostable than the wild type

SRC Holdings: Winning The Game While Sharing The Prize

SRC Holdings Corporation, formerly Springfield Remanufacturing Corp., is a well-known manufacturing enterprise comprised of numerous companies spread across 12 Business Units engaged in activities ranging from manufacturing to packaging to management consulting and training. However, their primary business expertise and core competency is remanufacturing -- the process of taking used transportation parts, for example, and returning them to their OEM (original equipment manufacturer) specifications. Headquartered in Springfield, Missouri, the SRC story is one of tremendous financial success, virtually from the beginning of the organization in 1983. At that time, a share of stock was worth 10¢; as of 2012, a single share is valued at about $361! But although the company is well-known for its financial record, it is safe to say that it is most famous for its founder and current CEO, Jack Stack, and his insistence on converting his company into an employee-owned firm very early on. The subsequent success of SRC and the role its employee stock ownership plan (ESOP) played in this success is legendary. Thus, it’s not surprising that both the SRC ESOP and Jack Stack play central roles in this case study

Optimal designs for stated choice experiments that incorporate ties

In 1970 Davidson generalised the Bradley-Terry model to allow respondents to say that the two options presented in a choice task were equally attractive. In this paper we extend this idea to the MNL model with m options in each choice set and we show that the optimal designs for the MNL model are also optimal in this setting. © 2009 Elsevier B.V. All rights reserved

Assessing the Felt Reports of the 1811-12 New Madrid Earthquakes in the Central United States

The damage and felt reports describing the New Madrid, Mo., earthquakes of 1811-12 need to be assessed in the historical context in which the events occurred. Log cabins in the frontier settlements along the lower Ohio River Valley, for example, were built with a rudimentary form of base isolation, and their response to the earthquakes should not be evaluated in the same way that a modern wood-frame or brick building would be. Also, inaccuracies have crept into the databases used for estimating the epicenters and magnitudes of the earthquakes. For example, the magnitude of the December 16, 1811, earthquake has been based, in part, on the lack of damage to buildings built well after the occurrence of the 1811-12 events, and the locations and circumstances of some of the people who described their observations of earthquakes and aftershocks in December 1811 while traveling down the Mississippi River on flatboats have been incorrectly used to estimate modified Mercalli intensities. This study indicates that the damage areas for the 1811-12 earthquakes have been underestimated, and favors an epicenter for the January 23, 1812, earthquake in the northern end of the new Madrid Fault Zone, and that the three aftershocks that some have suggested were triggered events centered in northeastern Kentucky or south-central Ohio were in fact centered in the New Madrid Seismic Zone

Book Reviews

Book Reviews of: Jonathan Schell, The Fate of the Earth (Alfred A. Knopf) John Updike, Rabbit is Rich (Alfred A. Knopf) George Gilder, Wealth and Poverty (Basic Book, Inc.

The Value of Literacy Practices

The concepts of literacy events and practices have received considerable attention in educational research and policy. In comparison, the question of value, that is, ‘which literacy practices do people most value?’ has been neglected. With the current trend of cross-cultural adult literacy assessment, it is increasingly important to recognise locally valued literacy practices. In this paper we argue that measuring preferences and weighting of literacy practices provides an empirical and democratic basis for decisions in literacy assessment and curriculum development and could inform rapid educational adaptation to changes in the literacy environment. The paper examines the methodological basis for investigating literacy values and its potential to inform cross-cultural literacy assessments. The argument is illustrated with primary data from Mozambique. The correlation between individual values and respondents’ socio-economic and demographic characteristics is explored

Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function

To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements made in vivo. Additional comparisons were made with a library constructed by error-prone PCR. Among the designed libraries, fluorescent function was preserved for the greatest fraction of samples in a library designed by using a structure-based computational method developed and described here. A trend was observed toward greater diversity of color in designed libraries that better preserved fluorescence. Contrary to trends observed among libraries constructed by error-prone PCR, preservation of function was observed to increase with a library's average mutation level among the four libraries designed with structure-based computational methods

Literacy under and over the desk: oppositions and heterogeneity

In this paper I argue that a dominant theme in New Literacy Studies research, the differences between literacy practices inside and outside school, has sometimes involved conflating ‘home literacy’ with private, unregulated ‘vernacular literacy’, and the use of an idealised abstract notion of schooled literacy to represent students’ actual everyday experience in the classroom. Drawing on linguistic ethnographic research in two British primary schools, I use examples of ‘unofficial’ and ‘official’ literacy activities from 10-11 year-olds to show that a wide range of different forms of literacy can be found in the classroom and I argue that the division between ‘vernacular’ and ‘schooled’ is not as clear-cut as is sometimes assumed. My analysis of children’s literacy activities suggests that, on the one hand, unofficial activities orientate towards and index official knowledges and the macro-level institutional order and, on the other hand, official activities are interpenetrated with informal practices and procedures. I also comment on some implications of using the New Literacy Studies ‘events and practices’ conceptual framework for understanding what is going on in classrooms

Modeling the choices of individual decision-makers by combining efficient choice experiment designs with extra preference information

We show how to combine statistically efficient ways to design discrete choice experiments based on random utility theory with new ways of collecting additional information that can be used to expand the amount of available choice information for modeling the choices of individual decision makers. Here we limit ourselves to problems involving generic choice options and linear and additive indirect utility functions, but the approach potentially can be extended to include choice problems with non-additive utility functions and non-generic/labeled options/attributes. The paper provides several simulated examples, a small empirical example to demonstrate proof of concept, and a larger empirical example based on many experimental conditions and large samples that demonstrates that the individual models capture virtually all the variance in aggregate first choices traditionally modeled in discrete choice experiments

Epistemic Schmagency?

Constructivist approaches in epistemology and ethics offer a promising account of normativity. But constructivism faces a powerful Schmagency Objection, raised by David Enoch. While Enoch’s objection has been widely discussed in the context of practical norms, no one has yet explored how the Schmagency Objection might undermine epistemic constructivism. In this paper, I rectify that gap. First, I develop the objection against a prominent form of epistemic constructivism, Belief Constitutivism. Belief Constitutivism is susceptible to a Schmagency Objection, I argue, because it locates the source of normativity in the belief rather than the agent. In the final section, I propose a version of epistemic constructivism that locates epistemic normativity as constitutive of agency. I argue that this version has the resources to respond to the Schmagency Objection