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Background: The Victorian Safe System approach to road safety slowly evolved from a combination of the Swedish Vision Zero philosophy and the Sustainable Safety model developed by the Dutch. The Safe System approach reframes the way in which road safety is viewed and managed., Methods: This paper presents a case study of the institutional change required to underpin the transformation to a holistic approach to planning and managing road safety in Victoria, Australia., Results: The adoption and implementation of a Safe System approach require strong institutional leadership and close cooperation among all the key agencies involved, and Victoria was fortunate in that it had a long history of strong interagency mechanisms in place. However, the challenges in the implementation of the Safe System strategy in Victoria are generally neither technical nor scientific; they are predominantly social and political. While many governments purport to develop strategies based on Safe System thinking, on-the-ground action still very much depends on what politicians perceive to be publicly acceptable, and Victoria is no exception., Conclusions: This is a case study of the complexity of institutional change and is presented in the hope that the lessons may prove useful for others seeking to adopt more holistic planning and management of road safety. There is still much work to be done in Victoria, but the institutional cultural shift has taken root. Ongoing efforts must be continued to achieve alert and compliant road users; however, major underpinning benefits will be achieved through focusing on road network safety improvements (achieving forgiving infrastructure, such as wire rope barriers) in conjunction with reviews of posted speed limits (to be set in response to the level of protection offered by the road infrastructure) and by the progressive introduction into the fleet of modern vehicle safety features., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Education is one of the strategies available to reduce traffic crashes and the resultant personal injury. It is seen by many as the major strategy for achieving lasting change. However, there is considerable debate as to the effectiveness of traffic safety education programs to date and, in an era when public expenditure is strongly influenced by the results of cost-benefit analyses, the more fundamental traffic safety education programs are under increasing challenge. The literature on effectiveness is indeed confusing. All too often, programs have commenced from a position of blind faith and have been implemented unsystematically, without specific objectives, targets, or evaluative milestones. The problem is compounded by the considerable methodological difficulties which confront the evaluators of long-term programs of behavior change. If traffic safety education is to survive as a viable countermeasure, program planning and execution must become far more scientific and evaluation must become an integral component. There is also an arguable case for the funds for the longer-term behavior change programs to come from the more general public health arena than from the narrower traffic safety field, while the short-term, specific educational programs should compete directly for funds with alternative traffic safety measures available for the given problem.

Small samples of the 8-S species of enzymes (A1 and A2) occurring in the DNA polymerase-alpha fraction of calf thymus, have been extensively purified using non-denaturing (normal) polyacrylamide gel electrophoresis. When peak fractions of activity on normal gels were subjected to dodecylsulphate-polyacrylamide gel electrophoresis, a polypeptide at 155000 correlated with polymerase activity. Samples of the 7.3-S (C) enzyme prepared from A2 by treatment with 2.4 M urea or isolated directly without exposure to urea, also showed the presence of a 155000-Mr polypeptide. It is concluded that the 7.3-S (C) enzyme, of previously estimated molecular weight 155000-170000, is a single polypeptide and that the 8-S enzymes A1 and A2 contain an additional subunit of 50000-70000 molecular weight.

The heterogeneity of calf thymus DNA polymerase-alpha has been further investigated. In particular, an enzyme (enzyme D) which exhibits higher activity on poly(dA) . (dT)10 (A:T = 20:1) compared with that on activated DNA, has been further purified and its properties compared with two other activities of the DNA polymerase-alpha fraction (enzymes A1 and C) which do not show a preference for poly(dA) . (dT)10 over activated DNA. As with A1 and C, enzyme D was shown to have many of the characteristic properties of DNA polymerase-alpha in that it is an acidic protein as judged by its binding to DEAE-cellulose, has a molecular weight of about 140000, does not use a poly (A) . (dT)10 template-initiator complex and is inhibited by N-ethylmaleimide. It exhibits anomalous gel filtration behaviour on Sepharose 6B and it binds relatively weakly to DNA-cellulose compared with DNA polymerase-beta. The extreme sensitivity of enzyme D to inhibtion by N-ethylmaleimide distinguishes it from A1 and C, as does its elution position from a DEAE-cellulose column. On the other hand enzymes C and D are readily inactivated by heating at 45 degrees C unlike enzyme A1. The possible interrelationships of the multiple activities of calf thymus DNA polymerase-alpha are discussed.

A DNA-dependent ATPase has been purified from calf thymus. The enzyme hydrolyses ATP and dATP in the presence of heat-denatured DNA. It does not hydrolyse the corresponding nucleoside triphosphates of guanine, uridine and cytosine. The Km values for ATP and dATP are both 0.62 mM. The enzyme requires magnesium or manganese ions. Its sedimentation coefficient is about 4.4 S. The catalytic activity is inhibited by N-ethylmaleimide but is not sensitive to novobiocin and nalidixic acid which are potent inhibitors of bacterial DNA gyrase. In some cases, during purification, chromatographically distinct additional DNA-dependent ATPase activities were detected. Limited proteolysis or covalent modification of the enzyme in the tissues, or during the first steps of its extraction, are probably responsible for the appearance of these chromatographically distinct forms.

The 5' flanking region of the CDC7 gene of Saccharomyces cerevisiae has been sequenced to a point 797 nucleotides upstream of the putative translational initiation codon (designated +1). The sequence reveals a number of symmetry elements between -100 to -380 and two blocks of high local AT content between -29 to -75 and -112 to -144. Transcription initiates heterogeneously at about 10 discrete sites up to 110 nucleotides upstream of the putative translational initiation codon. Some minor transcriptional start sites were also observed between the ATG at +1 and a second in-frame ATG at +55, suggesting that CDC7 may also be translationally heterogeneous. Deletion analysis of the CDC7 upstream region has shown that the gene lacks a functional TATA box, and has identified a 30bp element that is necessary for normal CDC7 promoter function during mitosis. This motif has significant homology with a component of the c-fos promoter which acts to regulate c-fos expression by binding a transcription activating factor. The results suggest that the 30bp motif may play a similar role in regulating CDC7 expression and that there may be similarities between factors that regulate CDC7 expression in yeast and c-fos expression in vertebrate cells.

The cell-division-cycle gene, CDC7, of Saccharomyces cerevisiae has been cloned in a large plasmid (pCM6) containing an insert of about 45 kb of yeast chromosomal DNA in the yeast-Escherichia coli shuttle vector, YRp7. A subclone (pCM39), having a 7-kb insert with a unique BamHI site, was capable of conferring the ts+ phenotype on a cdc7ts- strain of S. cerevisiae. When this insert was placed in the vector Y1p28, and then cut with BamHI and integrated into the ts- strain, genetic analysis showed the CDC7-complementing activity and an associated vector marker to be linked to the TRP1 locus, i.e., to chromosome IV. Analysis of subclones covering the pCM39 insert showed that pCM52, in which a 3.3-kb EcoRI-HpaI fragment with the unique BamHI site has been cloned, possessed the full complementing activity. Although the CDC7 gene lies across the BamHI site, the main part of the gene appears to be in the 2.2-kb BamHI-HpaI segment of the pCM52 insert. A Northern blot analysis showed this region to give rise to a 1.7-kb mRNA which we conclude is the transcript of CDC7. The large insert of pCM6 also contains a 1.5-kb XhoI fragment which several observations suggest is that containing the centromere (CEN4) of chromosome IV to which the CDC7 gene is closely linked. The 45-kb DNA fragment in pCM6 is believed to be an uninterrupted piece of chromosome IV.

1. A highly dextrorotatory polysaccharide (alpha(D)+232 degrees in n-sodium hydroxide), previously isolated as a fragment of Aspergillus niger cell walls, was prepared from whole mycelium and subjected to partial acid hydrolysis. 2. Fractionation of the hydrolysate on a charcoal column with a linear gradient of ethanol yielded a series of oligosaccharides. The disaccharide member was shown to be nigerose (3-O-alpha-d-glucopyranosyl-alpha-d-glucopyranose), although a small proportion of the disaccharide peak (10%) was present as maltose despite the fact that all the nigeran had been removed from the starting material. 3. The oligosaccharides forming the main peaks from the column were shown to be members of a polymer-homologous series (nigerodextrins) by (a) the relationship between the logarithm of their chromatographic mobility and degree of polymerization, (b) obeying the Freudenberg relationship, and (c) partial acid hydrolysis.

1. The activities of NMN adenylyltransferase and an enzyme that synthesizes poly (ADP-ribose) from NAD were investigated in the various classes of rat liver nuclei fractionated by zonal centrifugation. 2. The highest specific activities of these two nuclear enzymes occur in different classes of nuclei. In very young and in mature rats it was shown that a correlation exists between DNA synthesis and NMN adenylyltransferase activity, but in rats of intermediate age this correlation is less evident. The highest activities of the enzyme that catalyses formation of poly (ADP-ribose) are in the nuclei involved in the synthesis of RNA. 3. The significance of these results in relation to NAD metabolism is discussed.

1. Purified liver nuclei from adult rats separate into two main zones when centrifuged in the slow-speed zonal rotor. One zone contains diploid nuclei, the other tetraploid. 2. The effect of age on the pattern of rat liver ploidy was examined. Tetraploid nuclei are virtually absent from young animals. They increase in proportion steadily with age. Partial hepatectomy disturbs the pattern of ploidy. 3. The zonal centrifuge permits the separation of diploid, tetraploid, octaploid and hexadecaploid nuclei from mouse liver. 4. Rat liver nuclei are isopycnic with sucrose solutions of density 1.35 at 5 degrees .