Challenging Controversies: A Prospective Analysis of the Influence of New Technologies on the Safety of Offshore Drilling Operations

Integrated operations (IO) is an operating mode in the offshore oil and gas industry that is expected to lead to safer, faster and better operations. This article presents an analysis of the anticipated impacts of increased instrumentation on the safety of drilling operations. The instrumentation is related to the change process of IO, and is exemplified by a group of IO tools for interpretation, diagnosis and automation. An important finding in the study is the identification of a set of controversies that reflect characteristic challenges of drilling operations. These controversies involve the quantity and accessibility of information, the issue of centralized and decentralized control, the relation between standardized and unique interpretation of data, and the heterogeneous nature of engineering work. It is argued that the impact of the IO tools on safety will depend on how these controversies are taken into account when the tools are adopted. It is also argued that the cognitive control of the operations is distributed across a range of human and nonhuman actors and that the impact of the IO tools thus depends on how they are adapted to the system of distributed cognition rather than on the properties of the tools themselves.     

Crystallization and preliminary diffraction analysis of a truncated homodimer of human phenylalanine hydroxylase

A recombinant truncated form (delta1-102/delta428-452) of the non-heme iron-dependent metalloenzyme human phenylalanine hydroxylase (hPAH, phenylalanine 4-monooxygenase; EC 1.14.16.1) was expressed in E. coli, purified to homogeneity as a homodimer (70 kDa) and crystallized using the hanging drop vapour diffusion method. The crystals are orthorhombic, space group C222 with cell dimensions of a = 66.6 A, b = 108.4 A, c = 125.7 A. The calculated packing parameter (Vm) is 3.24 A3/Da with four 2-fold symmetric dimers (or eight momomers) in the unit cell. Data have been collected to 2.0 A resolution.     

Possible functions of peptide antibiotics during growth of producer organisms: bacitracin and metal (II) ion transport

The inhibitory effect of bacitracin upon growth of the producer strain Bacillus licheniformis ATCC 10716 was dependent upon the presence of several different metal (II) ions, particularly Mn (II), Co (II), or Zn (II) ions. This supports our previous suggestion that the normal function of bacitracin during growth of the producer organism may be to promote the uptake of several divalent metal ions. Due to the striking similarity between the antimicrobial effect of bacitracin towards susceptible organisms and the effect of bacitracin towards the producer organisms B. licheniformis ATCC 10716, the possibility that the antimicrobial effect of bacitracin may be an induction of uptake of toxic amounts of metal ions is discussed. The possibility that peptide antibiotics may normally participate in ion transport during growth of producer organisms is also discussed.     

L-DOPA is a substrate for tyrosine hydroxylase

In the presence of thiols, tyrosine hydroxylase (TH) oxidizes L-dihydroxyphenylalanine (L-DOPA) with a specific activity of up to 140 nmol min(-1) mg(-1) at 37 degrees C and pH 7.0, which is approximately 12-50% of its TH activity under similar experimental conditions. Using assay conditions that are optimal for measuring TH activity, the specific DOPA oxidase activity of human TH is similar to that of mushroom tyrosinase, but the two enzymes are clearly different in terms of substrate specificities, cofactor dependencies, and selectivity with respect to the effects of metal chelators and other inhibitors. In the presence of an excess of dithiothreitol, 2-mercaptoethanol, cysteine, or reduced glutathione, the reaction products of the two enzymes are identical and have been identified tentatively as thioether derivatives of DOPA. Theoretically, the oxidation of L-DOPA by TH may contribute to the formation of neuromelanin (pheomelanin) in catecholaminergic neurons and in the metabolism of DOPA to reactive intermediates that can react with free thiol groups in cellular proteins. The DOPA oxidase activity of TH can lead to errors in the estimation of in vivo or in vitro TH activity, and currently used assay protocols may have to be modified to avoid interference from this activity.     

“Seafarers should be navigating by the stars”: barriers to usability in ship bridge design

Cognition, Technology & Work - Navigating a ship is a complex task that requires close interaction between navigators and technology available on the ship’s bridge. The quality of this...     

Human tyrosine hydroxylase isoforms. Inhibition by excess tetrahydropterin and unusual behavior of isoform 3 after camp-dependent protein kinase phosphorylation

Human tyrosine hydroxylase exists as four isoforms (hTH1-4), generated by alternative splicing of pre-mRNA, with tissue-specific distribution. Unphosphorylated hTH3 and hTH1 were produced in large amounts in Escherichia coli and purified to homogeneity. The phosphorylation sites were determined after labeling with [32P]phosphate in the presence of cAMP-dependent protein kinase (PKA) and calmodulin-dependent protein kinase II (CaM-PKII). Ser40 was phosphorylated by PKA, and both Ser19 and Ser40 were phosphorylated by CaM-PKII. The enzyme kinetics of hTH3 were determined in the presence of various concentrations of the natural co-substrate (6R)-tetrahydrobiopterin and compared with those of recombinant hTH1 (similar to rat TH). We show that, under initial velocity conditions, excess (6R)-tetrahydrobiopterin inhibits hTH3 and hTH1. The TH catalytic constants (kcat) were determined for each of the two isoenzymes: hTH3 is about five times more active than hTH1. Phosphorylation by CaM-PKII did not affect the kinetic parameters of hTH3. The classical activation of TH by PKA phosphorylation, demonstrated for hTH1, was not observed with hTH3. Furthermore, hTH3 escapes activity regulation by phosphorylation and is always more active than phosphorylated hTH1. The properties of the hTH3 enzyme may be relevant to diseases affecting dopaminergic cells.     

Tyrosine hydroxylase and Parkinson's disease

A consistent neurochemical abnormality in Parkinson's disease (PD) is degeneration of dopaminergic neurons in substantia nigra, leading to a reduction of striatal dopamine (DA) levels. As tyrosine hydroxylase (TH) catalyses the formation of L-DOPA, the rate-limiting step in the biosynthesis of DA, the disease can be considered as a TH-deficiency syndrome of the striatum. Similarly, some patients with hereditary L-DOPA-responsive dystonia, a neurological disorder with clinical similarities to PD, have mutations in the TH gene and decreased TH activity and/or stability. Thus, a logical and efficient treatment strategy for PD is based on correcting or bypassing the enzyme deficiency by treatment with L-DOPA, DA agonists, inhibitors of DA metabolism, or brain grafts with cells expressing TH. A direct pathogenetic role of TH has also been suggested, as the enzyme is a source of reactive oxygen species (ROS) in vitro and a target for radical-mediated oxidative injury. Recently, it has been demonstrated that L-DOPA is effectively oxidized by mammalian TH in vitro, possibly contributing to the cytotoxic effects of DOPA. This enzyme may therefore be involved in the pathogenesis of PD at several different levels, in addition to being a promising candidate for developing new treatments of this disease.