15N NMR relaxation data reveal significant chemical exchange broadening in the alpha-domain of human α-lactalbumin

Human alpha-lactalbumin (alpha-LA), a 123-residue calcium-binding protein, has been studied using (15)N NMR relaxation methods in order to characterize backbone dynamics of the native state at the level of individual residues. Relaxation data were collected at three magnetic field strengths and analyzed using the model-free formalism of Lipari and Szabo. The order parameters derived from this analysis are generally high, indicating a rigid backbone. A total of 46 residues required an exchange contribution to T(2); 43 of these residues are located in the alpha-domain of the protein. The largest exchange contributions are observed in the A-, B-, D-, and C-terminal 3(10)-helices of the alpha-domain; these residues have been shown previously to form a highly stable core in the alpha-LA molten globule. The observed exchange broadening, along with previous hydrogen/deuterium amide exchange data, suggests that this part of the alpha-domain may undergo a local structural transition between the well-ordered native structure and a less-ordered molten-globule-like structure.

Characterization of human 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase gene and its expression in mammalian cells

Three β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD) catalyze the oxidative conversion of Δ5-3β-hydroxysteroids to the Δ4-3-keto configuration and is therefore essential for the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens. Using human 3β-HSD cDNA as probe, a human 3β-HSD gene was isolated from a λ-EMBL3 library of leucocyte genomic DNA. A fragment of 3β-HSD genomic DNA was also obtained by amplification of genomic DNA using the polymerase chain reaction. The 3β-HSD gene contains a 5′-untranslated exon of 53 base pairs (bp) and three successive translated exons of 232, 165, and 1218 bp, respectively, separated by introns of 129, 3883, and 2162 bp. The transcription start site is situated 267 nucleotides upstream from the ATG initiating codon. DNA sequence analysis of the 5′-flanking region reveals the existence of a putative TATA box (ATAAA) situated 28 nucleotides upstream from the transcription start site while a putative CAAT binding sequence is located 57 nucleotides upstream from the TATA box. Expression of a cDNA insert containing the coding region of 3β-HSD in nonsteroidogenic cells shows that the gene encodes a single 42-kDa protein containing both 3β-hydroxysteroid dehydrogenase and Δ5-Δ4-isomerase activities. Moreover, all natural steroid substrates tested are transformed with comparable efficiency by the enzyme. In addition to its importance for studies of the regulation of expression of 3β-HSD in gonadal as well as peripheral tissues, knowledge of the structure of the human 3β-HSD gene should permit investigation of the molecular defects responsible for 3β-HSD deficiency, the second most common cause of adrenal hyperplasia in children.

The development of an advanced ship evacuation simulation software product and associated large scale testing facility for the collection of human shipboard behaviour data

When designing a new passenger ship or modifying an existing design, how do we ensure that the proposed design and crew emergency procedures are safe from an evacuation point of view? In the wake of major maritime disasters such as the Herald of Free Enterprise and the Estonia and in light of the growth in the numbers of high density, high-speed ferries and large capacity cruise ships, issues concerned with the evacuation of passengers and crew at sea are receiving renewed interest. In the maritime industry, ship evacuation models offer the promise to quickly and efficiently bring evacuation considerations into the design phase, while the ship is "on the drawing board". maritimeEXODUS-winner of the BCS, CITIS and RINA awards - is such a model. Features such as the ability to realistically simulate human response to fire, the capability to model human performance in heeled orientations, a virtual reality environment that produces realistic visualisations of the modelled scenarios and with an integrated abandonment model, make maritimeEXODUS a truly unique tool for assessing the evacuation capabilities of all types of vessels under a variety of conditions. This paper describes the maritimeEXODUS model, the SHEBA facility from which data concerning passenger/crew performance in conditions of heel is derived and an example application demonstrating the models use in performing an evacuation analysis for a large passenger ship partially based on the requirements of MSC circular 1033.

The AASK Database V3.0: a database of human experience during aircraft evacuation incidents

This paper describes recent developments with the Aircraft Accident Statistics and Knowledge (AASK) database. The AASK database is a repository of survivor accounts from aviation accidents developed by the Fire Safety Engineering Group of the University of Greenwich with support from the UK CAA. Its main purpose is to store observational and anecdotal data from the actual interviews of the occupants involved in aircraft accidents. Access to the latest version of the database (AASK V3.0) is available over the Internet. AASK consists of information derived from both passenger and cabin crew interviews, information concerning fatalities and basic accident details. Also provided with AASK is the Seat Plan Viewer that graphically displays the starting locations of all the passengers - both survivors and fatalities - as well as the exits used by the survivors. Data entered into the AASK database is extracted from the transcripts supplied by the National Transportation Safety Board in the US and the Air Accident Investigation Branch in the UK. The quality and quantity of the data was very variable ranging from short summary reports of the accidents to boxes of individual accounts from passengers, crew and investigators. Data imported into AASK V3.0 includes information from 55 accidents and individual accounts from 1295 passengers and 110 crew.

An analysis of human behaviour during the WTC disaster of 9/11 based on published survivor accounts

This paper presents an analysis of survivor experiences from the World Trade Centre (WTC) evacuation of 11 September 2001. The experiences were collected from published accounts appearing in the print and electronic mass media and are stored in a relational database specifically developed for this purpose.

An Analysis of Human Behavior during Evacuation

The World Trade Center Evacuation: The evacuation of the WTC complex represents one of the largest full-scale evacuations of people in modern times.

The UK WTC 9/11 evacuation study: methodologies used in the elicitation and storage of human factors data

This paper describes the methodologies employed in the collection and storage of first-hand accounts of evacuation experiences derived from face-to-face interviews with evacuees from the World Trade Center (WTC) Twin Towers complex on 11 September 2001. In particular the paper describes the development of the High-rise Evacuation Evaluation Database (HEED). This is a flexible qualitative research tool which contains the full transcribed interview accounts and coded evacuee experiences extracted from those transcripts. The data and information captured and stored in the HEED database is not only unique, but it provides a means to address current and emerging issues relating to human factors associated with the evacuation of high-rise buildings.

A systematic methodology to assess the impact of human factors in ship design

Evaluating ship layout for human factors (HF) issues using simulation software such as maritimeEXODUS can be a long and complex process. The analysis requires the identification of relevant evaluation scenarios; encompassing evacuation and normal operations; the development of appropriate measures which can be used to gauge the performance of crew and vessel and finally; the interpretation of considerable simulation data. Currently, the only agreed guidelines for evaluating HFs performance of ship design relate to evacuation and so conclusions drawn concerning the overall suitability of a ship design by one naval architect can be quite different from those of another. The complexity of the task grows as the size and complexity of the vessel increases and as the number and type of evaluation scenarios considered increases. Equally, it can be extremely difficult for fleet operators to set HFs design objectives for new vessel concepts. The challenge for naval architects is to develop a procedure that allows both accurate and rapid assessment of HFs issues associated with vessel layout and crew operating procedures. In this paper we present a systematic and transparent methodology for assessing the HF performance of ship design which is both discriminating and diagnostic. The methodology is demonstrated using two variants of a hypothetical naval ship.

Methodologies employed in the collection, retrieval and storage of human factors information derived from first hand accounts of survivors of the WTC disaster of 11 September 2001

This article provides a broad overview of project HEED (High-rise Evacuation Evaluation Database) and the methodologies employed in the collection and storage of first-hand accounts of evacuation experiences derived from face-to-face interviews of evacuees from the World Trade Center (WTC) Twin Towers complex on September 11, 2001. In particular, the article describes the development of the HEED database. This is a flexible research tool which contains qualitative type data in the form of coded evacuee experiences along with the full interview transcripts. The data and information captured and stored in the HEED database is not only unique, but provides a means to address current and emerging issues relating to human factors associated with the evacuation of high-rise buildings