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The transcription factor GATA1 helps regulate the expression of thousands of genes involved in blood development, by binding to single or double GATA sites on DNA. An important part of gene activation is chromatin looping, the bringing together of DNA elements that lie up to many thousands of basepairs apart in the genome. It was recently suggested, based on studies of the closely related protein GATA3, that GATA-mediated looping may involve interactions of each of two zinc fingers (ZF) with distantly spaced DNA elements. Here we present a structure of the GATA1 ZF region bound to pseudopalindromic double GATA site DNA, which is structurally equivalent to a recently-solved GATA3-DNA complex. However, extensive analysis of GATA1-DNA binding indicates that although the N-terminal ZF (NF) can modulate GATA1-DNA binding, under physiological conditions the NF binds DNA so poorly that it cannot play a direct role in DNA-looping. Rather, the ability of the NF to stabilize transcriptional complexes through protein-protein interactions, and thereby recruit looping factors such as Ldb1, provides a more compelling model for GATA-mediated looping.

Despite its ubiquity in the systems engineering literature, flexibility remains an ambiguous concept. There exist a multitude of definitions, which vary not only by domain, but within domains as well. Furthermore, these definitions often conflict with one another, making it difficult to discern the intended meaning in a given study or to form generalizations across studies. Complicating matters, there is a plethora of related terminology that is often used carelessly and/or inter-changeably with flexibility. In this paper, we employ a novel ontological framework for clarifying salient aspects of extant flexibility-related terminology. While it was not possible to distill consensus definitions from the literature, we did identify certain dominant characteristics that enabled us to formulate a set of democratic definitions for flexibility, adaptability, and robustness, as well as recommended definitions for agility and versatility. We believe that the proposed definitions of these key system design principles may provide a baseline for improving analysis and communication among systems engineering practitioners and academics. © 2012 Wiley Periodicals, Inc. Syst Eng 16

For decades, the DoD has employed numerous reporting and monitoring tools for characterizing the acquisition cost estimates of its major programs. These tools have resulted in dozens of studies thoroughly documenting the magnitude and extent of DoD acquisition cost growth. However, little attention has been paid to the behavior of the larger cost component of a system's life cycle cost: Operating and Support (O&S) costs. Consequently, the DoD has little knowledge of how O&S cost estimates behave over time, and virtually no insights regarding their accuracy. In a previous paper, the authors describe an analytical methodology for remedying this deficiency via a study to characterize the historical accuracy of O&S cost estimates. The results of this study are presented here, and indicate there tend to be large errors in DoD O&S cost estimates, and that the accuracy of the estimates improves little over time. However, the results also suggest the possibility of improving the accuracy of these estimates via a stochastically-based predictive cost model.

The DOD routinely demonstrates its capability to develop phenomenal systems; however, these accomplishments are often tarnished by substantial cost and schedule overruns. While defense policies are continually being revised to address these problems, many believe that a more fundamental source of these overruns is the lack of flexibility in the systems being developed. But providing justification to invest in flexibility is a tough sell, as stakeholders struggle to quantitatively demonstrate the potential return on investment. Therefore, this paper introduces an alternative methodology for valuing the inherent ability of a system or design to accommodate change. The proposed methodology is essentially a modification of the current life cycle model and is premised on the notion that the need for capability changes in a program arise in a stochastic manner that can be incorporated into a continually updated, expected value model presented in terms of total program cost.

A method to assess product modularity using a vector approach is presented and demonstrated using two precision guided munitions. Modularity has several fundamental benefits agreed upon by industry including reusability, flexibility, reconfigurability and extensibility. Current modularity measures focus on interfaces within or between modules in provide/depend relationships. A new method that assesses the module interfaces as well as captures and addresses each of the recognized modularity benefits is presented in a Vector Modularity Measure (VMM). Components of the VMM include terms for degree of coupling, reusability, and flexibility. Flexibility is assessed in terms of reconfigurability and extensibility. The overall evaluation method is then summarized, followed by an application using two similar precision guided munitions in the U.S. Air Force inventory: the Guided Bomb Unit-24 (GBU-24), referred to as the laser guided bomb (LGB); and the Guided Bomb Unit-31 (GBU-31), referred to as the Joint Direct Attack Munition (JDAM).

The last decade has seen a dramatic increase in the use of small-angle scattering for the study of biological macromolecules in solution. The drive for more complete structural characterization of proteins and their interactions, coupled with the increasing availability of instrumentation and easy-to-use software for data analysis and interpretation, is expanding the utility of the technique beyond the domain of the biophysicist and into the realm of the protein scientist. However, the absence of publication standards and the ease with which 3D models can be calculated against the inherently 1D scattering data means that an understanding of sample quality, data quality, and modeling assumptions is essential to have confidence in the results. This review is intended to provide a road map through the small-angle scattering experiment, while also providing a set of guidelines for the critical evaluation of scattering data. Examples of current best practice are given that also demonstrate the power of the technique to advance our understanding of protein structure and function.

The systems engineering technical processes often lack the support of methods and tools that quantitatively integrate human considerations into early system design decisions. Because of this, engineers generally rely on qualitative judgments or delay critical decisions until late in the system lifecycle. Studies have revealed that this frequently results in cost, schedule, and effectiveness consequences. We begin this paper with a study of current issues in the application of systems engineering as a whole. We then examine how the challenges of human systems integration are a pervasive factor in those issues. Finally, we propose how to improve system engineering by better addressing the identified challenges.