The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

In the course of this reaction cycle the heme protein undergoes a series of changes of its coordination around the Fe (on reduction to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and upon introduction of the second reducing equivalent, as the heme protein returns to its original Fe3+ state}. Steroid substrates, inhibitors, and a variety of agents bind to the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine adrenal glands, with high affinities at sites near the heme group, but do not as a rule enter the coordination sphere of the Fe. This leads to perturbations of the electronic structure which can be followed by spectroscopic techniques (optical absorption, EPR spectroscopy) in combination with suitable chemical methods. Direct replacement of a ligand can also be achieved. The ferrous heme protein P450(Fe2+), in its unliganded and liganded forms, was also investigated. P450(Fe2•) combines readily with small ligands such as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic molecules (e. g. pyridine derivatives, other heterocyclic compounds, haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+), often with high affinities. They tend to enter the coordination sphere of the Fe and form stable complexes often with distinct optical absorption (440-470 nm); additional unspecific binding is frequently observed. Representative examples of the results for the various cases of interactions are presented and are discussed in relation to a hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX complex, with a thiol-group and a N-containing group as axial ligands; the observations are further related to the required changes in coordination in the course of the hydroxylation reaction

The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

In the course of this reaction cycle the heme protein undergoes a series of changes of its coordination around the Fe (on reduction to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and upon introduction of the second reducing equivalent, as the heme protein returns to its original Fe3+ state}. Steroid substrates, inhibitors, and a variety of agents bind to the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine adrenal glands, with high affinities at sites near the heme group, but do not as a rule enter the coordination sphere of the Fe. This leads to perturbations of the electronic structure which can be followed by spectroscopic techniques (optical absorption, EPR spectroscopy) in combination with suitable chemical methods. Direct replacement of a ligand can also be achieved. The ferrous heme protein P450(Fe2+), in its unliganded and liganded forms, was also investigated. P450(Fe2•) combines readily with small ligands such as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic molecules (e. g. pyridine derivatives, other heterocyclic compounds, haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+), often with high affinities. They tend to enter the coordination sphere of the Fe and form stable complexes often with distinct optical absorption (440-470 nm); additional unspecific binding is frequently observed. Representative examples of the results for the various cases of interactions are presented and are discussed in relation to a hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX complex, with a thiol-group and a N-containing group as axial ligands; the observations are further related to the required changes in coordination in the course of the hydroxylation reaction

Pseudopotential Approaches to Ca, Sr and Ba Hybrides. Why are some Alkaline Earth MX2_2 Compounds Bent?

Quasirelativistic and nonrelativistic lo-valence-electronp seudopotentialsf or Ca, Sr, and Ba are presented. Results of calculations with 6s6p5d basis sets for MH, MH$^+$ , and MH$_2$, are compared with all-electron and 2-valence-electron pseudopotential calculations with and , without core-polarization potentials. The lo-valence-electron pseudopotential approach agrees well with all-electron calculations. It circumvents problems for the 2-valence-electron pseudopotentials arising from an incomplete separation of valence and subvalence shells in polar molecular systems due to strongly contracted occupied (n - 1 )-d orbitals. All higherlevel calculations show SrH$_2$ and BaII$_2$, to be bent with angles of - 140° and 120°, respectively, while CaH$_2$ is linear with a flat potential-energy surface for the bending motion. The use of a core-polarization potential together with the 2-valence-electronp seudopotentiala pproach allows an investigation of the relative importance of core-polarization vs direct d-orbital bonding participation as reasons for the bent structures. The calculations strongly suggest that both contribute to the bending in SrH$_2$ and BaII$_2$. Even at the Hartree-Fock level of theory lovalence- electronp seudopotentialc alculations given reasonablea nglesw hen the potentialenergy surface is not exceedingly flat, and only moderately contracted basis sets including both compact d functions and diffuse p functions are used. The effect of core-valence correlation and the importance off functions also are discussed

Structure of Africa\u27s Southernmost Coral Communities

The structure of Africa\u27s southernmost coral communities, which grow on submerged fossil dune and beachrock systems and do not form true coral reefs, was quantitatively investigated by means of line transects and phototransects. None of the typical geomorphological reef-zones such as lagoons, reef crests or reef slopes were developed. A uniform community structure, differentiated only into two major community-types with three subcommunities, was found, Shallow reefs were dominated by alcyonaceans and differed from scleractinian dominated deep reefs. A high proportion of alcyonaceans was found in shallow communities (40–60%). Subcommunities, which were found on most reefs, were an alcyonacean dominated reef-top community in areas of low sedimentation, dominated by the genera Sinularia and Lobophytum, and a scleractinian dominated gully community (predominantly Montipora and Faviidae), in areas of high sedimentation. A deep sponge-dominated subcommunity existed on the deepest outcrops. The lower limit for most coral growth was between 35 and 40 m

Advancing cognitive engineering methods to support user interface design for electronic health records

Background Despite many decades of research on the effective development of clinical systems in medicine, the adoption of health information technology to improve patient care continues to be slow, especially in ambulatory settings. This applies to dentistry as well, a primary care discipline with approximately 137,000 practitioners in the United States. A critical reason for slow adoption is the poor usability of clinical systems, which makes it difficult for providers to navigate through the information and obtain an integrated view of patient data. Objective In this study, we documented the cognitive processes and information management strategies used by dentists during a typical patient examination. The results will inform the design of a novel electronic dental record interface. Methods We conducted a cognitive task analysis (CTA) study to observe ten general dentists (five general dentists and five general dental faculty members, each with more than two years of clinical experience) examining three simulated patient cases using a think-aloud protocol. Results Dentists first reviewed the patient’s demographics, chief complaint, medical history and dental history to determine the general status of the patient. Subsequently, they proceeded to examine the patient’s intraoral status using radiographs, intraoral images, hard tissue and periodontal tissue information. The results also identified dentists’ patterns of navigation through patient’s information and additional information needs during a typical clinician-patient encounter. Conclusion This study reinforced the significance of applying cognitive engineering methods to inform the design of a clinical system. Second, applying CTA to a scenario closely simulating an actual patient encounter helped with capturing participants’ knowledge states and decision-making when diagnosing and treating a patient. The resultant knowledge of dentists’ patterns of information retrieval and review will significantly contribute to designing flexible and task-appropriate information presentation in electronic dental records

Modelling of the low-impulse blast behaviour of fibre–metal laminates based on different aluminium alloys

A parametric study has been undertaken in order to investigate the influence of the properties of the aluminium alloy on the blast response of fibre–metal laminates (FMLs). The finite element (FE) models have been developed and validated using experimental data from tests on FMLs based on a 2024-O aluminium alloy and a woven glass–fibre/polypropylene composite (GFPP). A vectorized user material subroutine (VUMAT) was employed to define Hashin’s 3D rate-dependant damage constitutive model of the GFPP. Using the validated models, a parametric study has been carried out to investigate the blast resistance of FML panels based on the four aluminium alloys, namely 2024-O, 2024-T3, 6061-T6 and 7075-T6. It has been shown that there is an approximation linear relationship between the dimensionless back face displacement and the dimensionless impulse for all aluminium alloys investigated here. It has also shown that the residual displacement of back surface of the FML panels and the internal debonding are dependent on the yield strength of the aluminium alloy

Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

Localization of a 64-kDa phosphoprotein in the lumen between the outer and inner envelopes of pea chloroplasts

The identification and localization of a marker protein for the intermembrane space between the outer and inner chloroplast envelopes is described. This 64-kDa protein is very rapidly labeled by [γ-32P]ATP at very low (30 nM) ATP concentrations and the phosphoryl group exhibits a high turnover rate. It was possible to establish the presence of the 64-kDa protein in this plastid compartment by using different chloroplast envelope separation and isolation techniques. In addition comparison of labeling kinetics by intact and hypotonically lysed pea chloroplasts support the localization of the 64-kDa protein in the intermembrane space. The 64-kDa protein was present and could be labeled in mixed envelope membranes isolated from hypotonically lysed plastids. Mixed envelope membranes incorporated high amounts of 32P from [γ-32P]ATP into the 64-kDa protein, whereas separated outer and inner envelope membranes did not show significant phosphorylation of this protein. Water/Triton X-114 phase partitioning demonstrated that the 64-kDa protein is a hydrophilic polypeptide. These findings suggest that the 64-kDa protein is a soluble protein trapped in the space between the inner and outer envelope membranes. After sonication of mixed envelope membranes, the 64-kDa protein was no longer present in the membrane fraction, but could be found in the supernatant after a 110000 × g centrifugation

A preliminary model of work during initial examination and treatment planning appointments

Objective This study's objective was to formally describe the work process for charting and treatment planning in general dental practice to inform the design of a new clinical computing environment.Methods Using a process called contextual inquiry, researchers observed 23 comprehensive examination and treatment planning sessions during 14 visits to 12 general US dental offices. For each visit, field notes were analysed and reformulated as formalised models. Subsequently, each model type was consolidated across all offices and visits. Interruptions to the workflow, called breakdowns, were identified.Results Clinical work during dental examination and treatment planning appointments is a highly collaborative activity involving dentists, hygienists and assistants. Personnel with multiple overlapping roles complete complex multi-step tasks supported by a large and varied collection of equipment, artifacts and technology. Most of the breakdowns were related to technology which interrupted the workflow, caused rework and increased the number of steps in work processes.Conclusion Current dental software could be significantly improved with regard to its support for communication and collaboration, workflow, information design and presentation, information content, and data entry