An Assessment of the Effectiveness of Air Force Risk Management Practices in Program Acquisition Using Survey Instrument Analysis

Air Force acquisition programs invest a large amount of resources to develop and field systems. Many of these resources go to risk management in order to help ensure those programs finish successfully with respect to cost, schedule, and technical performance goals. The question arises as to whether this is a sound investment. Although risk management has been shown to be effective in industry, scant empirical evidence exists for its effectiveness within the Air Force. Correlation and regression analysis of survey data show that a positive relationship does exist between specific risk practices and project success. Furthermore, the analysis suggests that organizational behavior practices may reinforce that positive relationship in addition to the structured risk management steps prescribed by organizations such as the Department of Defense and the Project Management Institute

Bioinorganic Chemistry of Nickel

Note: In lieu of an abstract, this is an excerpt from the first page. Following the discovery of the first specific and essential role of nickel in biology in 1975 (the dinuclear active site of the enzyme urease) [1], nickel has become a major player in bioinorganic chemistry, particularly in microorganisms, having impacts on both environmental settings and human pathologies. At least nine classes of enzymes are now known to require nickel in their active sites, including catalysis of redox [(Ni,Fe) hydrogenases, carbon monoxide dehydrogenase, methyl coenzyme M reductase, acetyl coenzyme A synthase, superoxide dismutase] and nonredox (glyoxalase I, acireductone dioxygenase, lactate isomerase, urease) chemistries. In addition, the dark side of nickel has been illuminated in regard to its participation in microbial pathogenesis, cancer, and immune responses. Knowledge gleaned from the investigations of inorganic chemists into the coordination and redox chemistry of this element have boosted the understanding of these biological roles of nickel in each context. In this issue, eleven contributions, including four original research articles and seven critical reviews, will update the reader on the broad spectrum of the role of nickel in biology

Use of XAS for the elucidation of metal structure and function: applications to nickel biochemistry, molecular toxicology, and carcinogenesis.

Nickel has been shown to be an essential trace element involved in the metabolism of several species of bacteria, archea, and plants. In these organisms, nickel is involved in enzymes that catalyze both non-redox (e.g., urease, glyoxalase I) and redox (e.g., hydrogenase, carbon monoxide dehydrogenase, superoxide dismutase) reactions, and proteins involved in the transport, storage, metallocenter assembly, and regulation of nickel concentration have evolved. Studies of structure/function relationships in nickel biochemistry reveal that cysteine ligands are used to stabilize the Ni(III/II) redox couple. Certain nickel compounds have also been shown to be potent human carcinogens. A likely target for carcinogenic nickel is nuclear histone proteins. Here we present X-ray absorption spectroscopic studies of a model Ni peptide designed to help characterize the structure of the nickel complexes formed with histones and place them in the context of nickel structure/function relationships, to gain insights into the molecular mechanism of nickel carcinogenesis

Consequences of temperature fluctuations in observables measured in high energy collisions

We review the consequences of intrinsic, nonstatistical temperature fluctuations as seen in observables measured in high energy collisions. We do this from the point of view of nonextensive statistics and Tsallis distributions. Particular attention is paid to multiplicity fluctuations as a first consequence of temperature fluctuations, to the equivalence of temperature and volume fluctuations, to the generalized thermodynamic fluctuations relations allowing us to compare fluctuations observed in different parts of phase space, and to the problem of the relation between Tsallis entropy and Tsallis distributions. We also discuss the possible influence of conservation laws on these distributions and provide some examples of how one can get them without considering temperature fluctuations.Comment: Revised version of the invited contribution to The European Physical Journal A (Hadrons and Nuclei) topical issue about 'Relativistic Hydro- and Thermodynamics in Nuclear Physics' guest eds. Tamas S. Biro, Gergely G. Barnafoldi and Peter Va

Bioinorganic Chemistry of Nickel

Following the discovery of the first specific and essential role of nickel in biology in 1975 (the dinuclear active site of the enzyme urease) [...

Nonredox Nickel Enzymes

The importance of nickel enzymes, where nickel serves as an essential cofactor, in Archaea, bacteria, plants, and primitive eukaryotes, is well documented. Despite the fact that no enzyme utilizing Ni has been found in mammalian species, the impact of Ni biochemistry on human health is also significant. Indeed, nickel is known to cause cancer by an epigenetic mechanism, which appears to involve substitution of Ni(II) for Fe(II) in non- heme iron dioxygenases that are involved in DNA and histone demethylation. Furthermore, exposure to nickel compounds can also elicit an immune reaction: nickel contact dermatitis is one of the most common allergies in the modern world,5 and the molecular basis for the immune reaction is now beginning to emerge. Exposure to high levels of nickel has also been shown to impair the normal homeostasis of essential metal ions. Nonetheless, nickel is among the metals included in a group of “possibly essential elements” for animals and humans. Experiments using animal models have shown that nickel may be beneficial for bone composition and strength, for optimal reproduction, for energy metabolism, and for sensory function. The molecular basis for these functions is, however, not known. It is not surprising that human nickel deficiency has never been reported, probably because normal nickel intake greatly exceeds the estimated 25−35 μg/day metabolic requirement. In this Review, the current knowledge of the biochemistries, structures, and reaction mechanisms of enzymes whose active sites require nickel, and utilize it in a nonredox role, are discussed. In addition to excluding redox-active nickel sites (see the pertinent Reviews in this Thematic Issue), proteins isolated in proteomics facilities using nickel affinity columns that contain nickel, but whose native active site does not contain nickel, are also excluded. The focus is on the enzymes, and data from synthetic model systems is included only when it enhances knowledge of the reaction mechanism. The selection of nickel as a catalytic center for biological reactions is related to its flexible coordination geometry, which makes this metal a very versatile element for biological applications. To date, eight microbial nickel-containing enzymes have been well-characterized, including urease, hydrogenase, CO-dehydrogenase, acetyl-CoA synthase, methyl-CoM reductase, Ni-superoxide dismutase, acireductone dioxygenase, and glyoxalase I, while a few other possible nickel-dependent enzymes are emerging. The biological roles of nickel enzymes are conveniently divided into redox and nonredox roles. Unlike the more abundant biological redox metals iron and copper, aquated Ni(II) ions have no biologically relevant redox chemistry, as water will oxidize and reduce at potentials less extreme than those of the metal ion. Thus, the ligand environment is critical in adjusting the redox potential of Ni(II) into a biologically accessible range. In terms of nickel enzymes, this is usually achieved via coordination of anionic S-donors such as sulfide (as in carbon monoxide dehydrogenase) or, more commonly, thiolate sulfur in the form of cysteine ligands, which stabilizes the Ni(II/III) redox couple, or by coupling processes to sulfur redox chemistry (e.g., in methyl coenzyme M reductase). Thus, S-donor ligands are strongly associated with Ni redox enzymes, which include a novel superoxide dismutase, and several other enzymes including hydrogenase and CO- dehydrogenase/acetyl coenzyme A synthase that use Ni(II/III) redox chemistry to catalyze reactions that are involved in biological C1 chemistry. These enzymes have been extensively reviewed recently, and are covered by Reviews elsewhere in this Thematic Issue (see Valentine et al., Lubitz, and Ragsdale). In addition to adjusting redox potentials, the S-donor rich ligand environments often favor coordinatively unsaturated complexes with low-spin electronic structures. Nickel is also employed in enzymes as a Lewis acid catalyst, and in contrast to the redox enzymes, the coordination environments of these enzymes are composed exclusively of O/N-donor ligands. The coordination chemistry typically favors six-coordinate Ni(II) complexes that invariably have high-spin electronic structures. Three enzymes that utilize Ni(II) as a Lewis acid, urease, acireductone dehydrogenase, and glyoxalase I, are discussed here, with the goal of updating other comprehensive reviews through mid-2013

An XAS investigation of the nickel site structure in the transcriptional regulator InrS

InrS (Internal nickel-responsive Sensor) is a transcriptional repressor of the nickel exporter NrsD and de-represses expression of the exporter upon binding Ni(II) ions. Although a crystal structure of apo-InrS has been reported, no structure of the protein with metal ions bound is available. Herein we report the results of metal site structural investigations of Ni(II) and Cu(II) complexes of InrS using X-ray absorption spectroscopy (XAS) that are complementary to data available from the apo-InrS crystal structure, and are consistent with a planar four-coordinate [Ni(His)2(Cys)2] structure, where the ligands are derived from the side chains of His21, Cys53, His78, and Cys82. Coordination of Cu(II) to InrS forms a nearly identical planar four-coordinate complex that is consistent with a simple replacement of the Ni(II) center by Cu(II)

The PqrR Transcriptional Repressor of Pseudomonas aeruginosa Transduces Redox Signals via an Iron-Containing Prosthetic Group▿ †

Inducible defenses against oxidative stress are coordinated by redox-sensitive transcription factors that transduce oxidative damage into differential gene expression. The opportunistic human pathogen Pseudomonas aeruginosa has evolved under physiological and host-derived sources of oxidative stress. Previous work showed that the pqrABC and pqrR genes of P. aeruginosa, all lacking known functions, were induced by treatment of three different isolates of P. aeruginosa with paraquat (PQ), a superoxide-producing agent. Insertional mutation of the pqrABCR genes resulted in hypersensitive phenotypes to a variety of oxidants, although the hypersensitivity to PQ was marginal. Mutation of pqrR and complementation assays showed that PqrR regulated the pqrABC genes in response to PQ. PqrR, a member of the MarR family of transcriptional regulators, contains a C-terminal region with four conserved cysteines, which suggested redox-regulated transcriptional activity. Purified PqrR bound to two discrete sites at the pqrA and pqrR regulatory regions. The in vitro DNA binding activity of PqrR was decreased by exposure to air and reconstituted by treatment with dl-dithiothreitol. Elemental analysis and preliminary electron paramagnetic resonance experiments showed that PqrR contains iron. Interestingly, site-directed mutagenesis of C-terminal cysteines demonstrated that the four conserved cysteine residues are essential for in vivo redox sensing by PqrR