A novel device using the Nordic hamstring exercise to assess eccentric knee flexors strength : a reliability and retrospective injury study

STUDY DESIGN: Reliability and case-control injury study. OBJECTIVES: 1) To determine if a novel device, designed to measure eccentric knee flexors strength via the Nordic hamstring exercise (NHE), displays acceptable test-retest reliability; 2) to determine normative values for eccentric knee flexors strength derived from the device in individuals without a history of hamstring strain injury (HSI) and; 3) to determine if the device could detect weakness in elite athletes with a previous history of unilateral HSI. BACKGROUND: HSIs and reinjuries are the most common cause of lost playing time in a number of sports. Eccentric knee flexors weakness is a major modifiable risk factor for future HSIs, however there is a lack of easily accessible equipment to assess this strength quality. METHODS: Thirty recreationally active males without a history of HSI completed NHEs on the device on 2 separate occasions. Intraclass correlation coefficients (ICCs), typical error (TE), typical error as a co-efficient of variation (%TE), and minimum detectable change at a 95% confidence interval (MDC95) were calculated. Normative strength data were determined using the most reliable measurement. An additional 20 elite athletes with a unilateral history of HSI within the previous 12 months performed NHEs on the device to determine if residual eccentric muscle weakness existed in the previously injured limb. RESULTS: The device displayed high to moderate reliability (ICC = 0.83 to 0.90; TE = 21.7 N to 27.5 N; %TE = 5.8 to 8.5; MDC95 = 76.2 to 60.1 N). Mean±SD normative eccentric flexors strength, based on the uninjured group, was 344.7 ± 61.1 N for the left and 361.2 ± 65.1 N for the right side. The previously injured limbs were 15% weaker than the contralateral uninjured limbs (mean difference = 50.3 N; 95% CI = 25.7 to 74.9N; P < .01), 15% weaker than the normative left limb data (mean difference = 50.0 N; 95% CI = 1.4 to 98.5 N; P = .04) and 18% weaker than the normative right limb data (mean difference = 66.5 N; 95% CI = 18.0 to 115.1 N; P < .01). CONCLUSIONS: The experimental device offers a reliable method to determine eccentric knee flexors strength and strength asymmetry and revealed residual weakness in previously injured elite athletes.

FP01-5 Pregnancy loss and psychiatric disorders in young men and women : results from Australian longitudinal cohort study

Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Little is known about later adverse psychiatric outcomes in young men whose partners have fallen pregnant and either go on to have a child, have an abortion or miscarry. 1223 women and 1159 men, from an Austrailan cohort born between 1981 and 1984, were assessed at 21 years for psychiatric and substance misuse and lifetime pregnancy histories. Young women reporting a pregnancy loss (either miscarriage or abortion) had nearly three times the odds of experiencing a illicit drug disorder (excluding cannabis), and nearly twice the odds of an alcohol misuse compared to never pregnant women. Young men whose partner had an abortion, but not a miscarriage, had nearly twice the odds of cannabis disorder, illicit drug disorder, and mood disorder compared to men that had never fathered a pregnancy. Young women who have lost a pregnancy have an increased risk of developing alcohol or substance abuse in later life. Young men whose partner aborted a pregnancy only had an increased of substance abuse and mood disorder in later life. These findings add to the growing body of evidence suggesting that pregnancy loss per se increases the risk of a range of substance use disorders in young women. The findings for young men are novel and raise the possibility that the associations measured may be due to common unmeasured factors associated with early pregnancy in young people rather than pregnancy loss.

High altitude stereo visual odometry

Stereo visual odometry has received little investigation in high altitude applications due to the generally poor performance of rigid stereo rigs at extremely small baseline-to-depth ratios. Without additional sensing, metric scale is considered lost and odometry is seen as effective only for monocular perspectives. This paper presents a novel modification to stereo based visual odometry that allows accurate, metric pose estimation from high altitudes, even in the presence of poor calibration and without additional sensor inputs. By relaxing the (typically fixed) stereo transform during bundle adjustment and reducing the dependence on the fixed geometry for triangulation, metrically scaled visual odometry can be obtained in situations where high altitude and structural deformation from vibration would cause traditional algorithms to fail. This is achieved through the use of a novel constrained bundle adjustment routine and accurately scaled pose initializer. We present visual odometry results demonstrating the technique on a short-baseline stereo pair inside a fixed-wing UAV flying at significant height (~30-100m).

What is a good project manager? Reconceptualizing the “do” : an Aristotelian perspective

In Social Science (Organization Studies, Economics, Management Science, Strategy, International Relations, Political Science…) the quest for addressing the question “what is a good practitioner?” has been around for centuries, with the underlying assumptions that good practitioners should lead organizations to higher levels of performance. Hence to ask “what is a good “captain”?” is not a new question, we should add! (e.g. Tsoukas & Cummings, 1997, p. 670; Söderlund, 2004, p. 190). This interrogation leads to consider problems such as the relations between dichotomies Theory and Practice, rigor and relevance of research, ways of knowing and knowledge forms. On the one hand we face the “Enlightenment” assumptions underlying modern positivist Social science, grounded in “unity-of-science dream of transforming and reducing all kinds of knowledge to one basic form and level” and cause-effects relationships (Eikeland, 2012, p. 20), and on the other, the postmodern interpretivist proposal, and its “tendency to make all kinds of knowing equivalent” (Eikeland, 2012, p. 20). In the project management space, this aims at addressing one of the fundamental problems in the field: projects still do not deliver their expected benefits and promises and therefore the socio-economical good (Hodgson & Cicmil, 2007; Bredillet, 2010, Lalonde et al., 2012). The Cartesian tradition supporting projects research and practice for the last 60 years (Bredillet, 2010, p. 4) has led to the lack of relevance to practice of the current conceptual base of project management, despite the sum of research, development of standards, best & good practices and the related development of project management bodies of knowledge (Packendorff, 1995, p. 319-323; Cicmil & Hodgson, 2006, p. 2–6, Hodgson & Cicmil, 2007, p. 436–7; Winter et al., 2006, p. 638). Referring to both Hodgson (2002) and Giddens (1993), we could say that “those who expect a “social-scientific Newton” to revolutionize this young field “are not only waiting for a train that will not arrive, but are in the wrong station altogether” (Hodgson, 2002, p. 809; Giddens, 1993, p. 18). While, in the postmodern stream mainly rooted in the “practice turn” (e.g. Hällgren & Lindahl, 2012), the shift from methodological individualism to social viscosity and the advocated pluralism lead to reinforce the “functional stupidity” (Alvesson & Spicer, 2012, p. 1194) this postmodern stream aims at overcoming. We suggest here that addressing the question “what is a good PM?” requires a philosophy of practice perspective to complement the “usual” philosophy of science perspective. The questioning of the modern Cartesian tradition mirrors a similar one made within Social science (Say, 1964; Koontz, 1961, 1980; Menger, 1985; Warry, 1992; Rothbard, 1997a; Tsoukas & Cummings, 1997; Flyvbjerg, 2001; Boisot & McKelvey, 2010), calling for new thinking. In order to get outside the rationalist ‘box’, Toulmin (1990, p. 11), along with Tsoukas & Cummings (1997, p. 655), suggests a possible path, summarizing the thoughts of many authors: “It can cling to the discredited research program of the purely theoretical (i.e. “modern”) philosophy, which will end up by driving it out of business: it can look for new and less exclusively theoretical ways of working, and develop the methods needed for a more practical (“post-modern”) agenda; or it can return to its pre-17th century traditions, and try to recover the lost (“pre-modern”) topics that were side-tracked by Descartes, but can be usefully taken up for the future” (Toulmin, 1990, p. 11). Thus, paradoxically and interestingly, in their quest for the so-called post-modernism, many authors build on “pre-modern” philosophies such as the Aristotelian one (e.g. MacIntyre, 1985, 2007; Tsoukas & Cummings, 1997; Flyvbjerg, 2001; Blomquist et al., 2010; Lalonde et al., 2012). It is perhaps because the post-modern stream emphasizes a dialogic process restricted to reliance on voice and textual representation, it limits the meaning of communicative praxis, and weaking the practice because it turns away attention from more fundamental issues associated with problem-definition and knowledge-for-use in action (Tedlock, 1983, p. 332–4; Schrag, 1986, p. 30, 46–7; Warry, 1992, p. 157). Eikeland suggests that the Aristotelian “gnoseology allows for reconsidering and reintegrating ways of knowing: traditional, practical, tacit, emotional, experiential, intuitive, etc., marginalised and considered insufficient by modernist [and post-modernist] thinking” (Eikeland, 2012, p. 20—21). By contrast with the modernist one-dimensional thinking and relativist and pluralistic post-modernism, we suggest, in a turn to an Aristotelian pre-modern lens, to re-conceptualise (“re” involving here a “re”-turn to pre-modern thinking) the “do” and to shift the perspective from what a good PM is (philosophy of science lens) to what a good PM does (philosophy of practice lens) (Aristotle, 1926a). As Tsoukas & Cummings put it: “In the Aristotelian tradition to call something good is to make a factual statement. To ask, for example, ’what is a good captain’?’ is not to come up with a list of attributes that good captains share (as modem contingency theorists would have it), but to point out the things that those who are recognized as good captains do.” (Tsoukas & Cummings, 1997, p. 670) Thus, this conversation offers a dialogue and deliberation about a central question: What does a good project manager do? The conversation is organized around a critic of the underlying assumptions supporting the modern, post-modern and pre-modern relations to ways of knowing, forms of knowledge and “practice”.

Evidence for the adsorption of molecules at special sites located at copper/zinc oxide interfaces. Part 2. -- A fourier-transform infrared spectroscopy study of methanol adsorption on reduced and oxidised Cu/ZnO/SiO2 catalysts

FTIR spectra are reported of methanol adsorbed at 295 K on ZnO/SiO 2, on reduced Cu/ZnO/SiO2 and on Cu/ZnO/SiO2 which had been preoxidised by exposure to nitrous oxide. Methanol on ZnO/SiO2 gave methoxy species on ZnO and SiO, in addition to both strongly and weakly physisorbed methanol on SiO2. The corresponding adsorption of methanol on reduced Cu/ZnO/SiO2 also gave methoxy species on Cu and a small amount of bridging formate. Reaction of methanol with a reoxidised Cu/ZnO/SiO2 catalyst resulted in an enhanced quantity of methoxy species on Cu. Heating adsorbed species on Cu/ZnO/SiO2 at 393 K led to the loss of methoxy groups on Cu and the concomitant formation of formate species on both ZnO and Cu. The comparable reaction on a reoxidised Cu/ZnO/SiO2 catalyst gave an increased amount of formate species on ZnO and this correlated with an increased quantity of methoxy groups lost from Cu. An explanation is given in terms of adsorption of formate and formaldehyde species at special sites located at the copper/zinc oxide interface.

Passenger familiarity and intuitive navigation within airport environments

Passengers navigating through airports can experience confusion or become lost, resulting in dissatisfaction, missed flights and flight delays. Passengers moving through airports are required to make many navigation decisions, for example to find the correct check-in desk or find the correct boarding gate. Prior experience of using the airports is likely to enable intuitive navigation, however limited research on this topic currently exists. In this paper we investigate passenger navigation by observing 30 participants at one international airport as they moved from check-in to a departure gate. The results indicate that passengers do spend time navigating intuitively through the airport, and that there is a positive correlation between intuitive navigation and airport familiarity. It was also found that participants with lower airport familiarity spend a greater percentage of overall navigation time searching and assessing/acquiring information than high familiarity participants. These findings provide evidence that passengers with higher airport familiarity have a greater understanding of the process, have a better understanding of what information to look for and use this familiarity to navigate intuitively. Findings from this research will have design implications for both current, and future airport terminals and other large spaces that people navigate through.

PEGylation of lysine residues reduces the pro-migratory activity of IGF-I

Background: The insulin-like growth factor (IGF) system is composed of ligands and receptors which regulate cell proliferation, survival, differentiation and migration. Some functions are regulated via intracellular signaling cascades, others by involvement of the extracellular milieu, including binding proteins and other extracellular matrix proteins. However, understanding of their functions and the exact nature of these interactions remains incomplete. Methods: IGF-I was PEGylated at its lysine sites - K27, K65 and K68. Binding of PEG-IGF-I to the IGFBPs was analyzed using BIAcore and its ability to activate the IGF-IR was assessed using IGF-IR phosphorylation assay. Furthermore, functional consequences of PEGylating the lysine residues of IGF-I was investigated using cell viability and cell migration assays. In addition, particular downstream signaling pathways regularly implicated in these mechanisms were also dissected using phospho-AKT and phospho-ERK1/2 assays. Results: In this study, IGF-I specifically PEGylated at lysine 27 (PEG-K27), 65 (PEG-K65) or 68 (PEG-K68) were employed. Receptor phosphorylation was only reduced by 2-fold with PEG-K65 and PEG-K68 over all the time points tested, and as observed in two cell types, 3T3 fibroblasts and MCF-7 breast cancer cells. PEGylation at K27 resulted in a much larger effect, with more than 10-fold lower activation for 3T3 fibroblasts and a ~3 fold reduced IGF-IR activation for MCF-7 breast cancer cells over 15 minutes. In addition, all PEG-IGF-I variants demonstrated a ten-fold reduction in the association rate to IGF binding proteins (IGFBPs). Functionally, all PEG variants completely lost their ability to induce cell migration in the presence of IGFBP-3/vitronectin (VN) complexes as compared to IGF-I; in contrast, cell viability was fully preserved. Further investigations into the downstream signaling pathways revealed that the PI3-K/AKT pathway was preferentially affected upon treatment with the PEG-IGF-I variants compared to the MAPK/ERK pathway. Conclusion: PEGylation of IGF-I has an impact on cell migration but not cell viability. General significance: PEG-IGF-I may differentially modulate IGF-I mediated functions that are dependent on its interaction with its receptor as well as key extracellular proteins such as VN and IGFBPs.

BoP and MNCs: where is the market and where the source of innovation?

ln 2004 Prahalad made managers aware of the great economic opportunity that the population at the BoP (Base of the Pyramid) could represent for business in the tom of new potential consumers. However, MNCs (Multi-National Corporations) have continued to fail in penetrating low income markets, arguably because applied strategies are often the same adopted at the top of the pyramid. Even in those few cases where products get re-envisioned, theie introduction in contexts of extreme poverty only induces new needs and develops new dependencies. At best the rearrangement of business models by MNCs has meant the realization of CSR (Corporate Social Responsibly) schemes that have validity from a marketing perspective, but still lack the crucial element of social embeddedness (London & Hart, 2004). Today the challenge is lo reach the lowest population tier with reinvented business models based on principles of value co-creation. Starting from a view of the potential consumer at the BoP as a ring of continuity in the value chain process – a resource that can itself produce value - this paper concludes proposing an alternative innovative approach to operate in developing markets that overturns the roles of MNCs and the BoP. The proposed perspective of ‘reversed' source of innovation and primary target market builds on two fundamental tenets: traditional knowledge is rich and greatly unexploded, and markets at the lop of the pyramid are saturated with unnecessary products / practices that have lost contact with the natural environment.

BoP and MNCs: where is the market and where the source of innovation?

ln 2004 Prahalad made managers aware of the great economic opportunity that the population at the BoP (Base of the Pyramid) could represent for business in the tom of new potential consumers. However, MNCs (Multi-National Corporations) have continued to fail in penetrating low income markets, arguably because applied strategies are often the same adopted at the top of the pyramid. Even in those few cases where products get re-envisioned, theie introduction in contexts of extreme poverty only induces new needs and develops new dependencies. At best the rearrangement of business models by MNCs has meant the realization of CSR (Corporate Social Responsibly) schemes that have validity from a marketing perspective, but still lack the crucial element of social embeddedness (London & Hart, 2004). Today the challenge is lo reach the lowest population tier with reinvented business models based on principles of value co-creation. Starting from a view of the potential consumer at the BoP as a ring of continuity in the value chain process – a resource that can itself produce value - this paper concludes proposing an alternative innovative approach to operate in developing markets that overturns the roles of MNCs and the BoP. The proposed perspective of ‘reversed' source of innovation and primary target market builds on two fundamental tenets: traditional knowledge is rich and greatly unexploded, and markets at the lop of the pyramid are saturated with unnecessary products / practices that have lost contact with the natural environment.

Getting published — and cited in entrepreneurship : reflections on ten papers

I grew up in academic heaven. At least for me it was. Not only was Sweden in the late 1980s paradise for any kind of empirical research, with rich and high-quality business statistics being made available to researchers without them having to sign away their lives; 70+ percent response rates achieved in mail surveys to almost any group (if you knew how to do them), and boards of directors opening their doors to more qualitatively orientated researchers to sit in during their meetings. In addition, I perceived an environment with a very high degree of academic freedom, letting me do whatever I found interesting and important. I’m sure for others it was sheer hell, with very unclear career paths and rules of the game. Career progression (something which rarely entered my mind) meant that you tried as best you could and then you put all your work – reports, books, book chapters, conference papers, maybe even published articles – in a box and had some external committee of professors look at it. If you were lucky they liked what they saw for whatever reasons their professorial wisdom dictated, and you got hired or promoted. If you were not so lucky you wouldn’t get the job or the promotion, without quite knowing why. So people could easily imagine an old boys club – whose members were themselves largely unproven in international, peer review publishing – picking whoever they wanted by whatever criteria they choose to apply. Neither the fact that assessors were external nor the presence of an appeals system might have completely appeased your suspicious and skeptical mind, considering the balance of power.

Influence of nitrogen fertiliser application and timing on greenhouse gas emissions from a lychee (Litchi chinensis) orchard in humid subtropical Australia

Nitrous oxide emissions from intensive, fertilised agricultural systems have been identified as significant contributors to both Australia's and the global greenhouse gas (GHG) budget. This is expected to increase as rates of agriculture intensification and land use change accelerate to support population growth and food production. Limited data exists on N2O trace gas fluxes from subtropical or tropical tree cropping soils critical for the development of effective mitigation strategies.This study aimed to quantify GHG emissions over two consecutive years (March 2007 to March 2009) from a 30 year (lychee) orchard in the humid subtropical region of Australia. GHG fluxes were measured using a combination of high temporal resolution automated sampling and manually sampled chambers. No fertiliser was added to the plots during the 2007 measurement season. A split application of nitrogen fertiliser (urea) was added at the rate of 265kgNha-1 during the autumn and spring of 2008. Emissions of N2O were influenced by rainfall events and seasonal temperatures during 2007 and the fertilisation events in 2008. Annual N2O emissions from the lychee canopy increased from 1.7kgN2O-Nha-1yr-1 for 2007, to 7.6kgN2O-Nha-1yr-1 following fertiliser application in 2008. This represented an emission factor of 1.56%, corrected for background emissions. The timing of the split application was found to be critical to N2O emissions, with over twice as much lost following an application in spring (2.44%) compared to autumn (EF: 1.10%). This research suggests that avoiding fertiliser application during the hot and moist spring/summer period can reduce N2O losses without compromising yields.

Fabrication and in vitro characterisation of bioactive glass composite scaffolds for bone regeneration

Here we fabricate and characterise bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilising additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young’s modulus compared to PCL scaffolds at similar porosity (~75%). After 1 day in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ±3.8%, 12.1 ±1% and 1.6 ±1% of its original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralisation when compared to PCL scaffolds. However, as indicated by ALP activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffold shows potential as a next generation bone scaffold.

A poly(lactic-co-glycolic acid) knitted scaffold for tendon tissue engineering: an in vitro and in vivo study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

Cyclin A/CDK2 regulates multiple G2 phase pathways

The cell cycle is a carefully choreographed series of phases that when executed successfully will allow the complete replication of the genome and the equal division of the genome and other cellular content into two independent daughter cells. The inability of the cell to execute cell division successfully can result in either checkpoint activation to allow repair and/or apoptosis and/or mutations/errors that may or may not lead to tumourgenesis. Cyclin A/CDK2 is the primary cyclin/CDK regulating G2 phase progression of the cell cycle. Cyclin A/CDK2 activity peaks in G2 phase and its inhibition causes a G2 phase delay that we have termed 'the cyclin A/CDK2 dependent G2 delay'. Understanding the key pathways that are involved in the cyclin A/CDK2 dependent G2 delay has been the primary focus of this study. Characterising the cyclin A/CDK2 dependent G2 delay revealed accumulated levels of the inactive form of the mitotic regulator, cyclin B/CDK1. Surprisingly, there was also increased microtubule nucleation at the centrosomes, and the centrosomes stained for markers of cyclin B/CDK1 activity. Both microtubule nucleation at the centrosomes and phosphoprotein markers were lost with short-term treatment of CDK1/2 inhibition. Cyclin A/CDK2 localised at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Thus G2 phase cyclin A/CDK2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/CDK1, but also has an unexpected role in coordinating the activation of cyclin B/CDK1 at the centrosome and in the nucleus. In addition to regulating the timing of cyclin B/CDK1 activation and entry into mitosis in the unperturbed cell cycle, cyclin A/CDK2 also was shown to have a role in G2 phase checkpoint recovery. Known G2 phase regulators were investigated to determine whether they had a role in imposing the cyclin A/ CDK2 dependent G2 delay. Examination of the critical G2 checkpoint arrest protein, Chk1, which also has a role during unperturbed G2/M phases revealed the presence of activated Chk1 in G2 phase, in a range of cell lines. Activated Chk1 levels were shown to accumulate in cyclin A/CDK2 depleted/inhibited cells. Further investigations revealed that Chk1, but not Chk2, depletion could reverse the cyclin A/CDK2 dependent G2 delay. It was confirmed that the accumulative activation of Chk1 was not a consequence of DNA damage induced by cyclin A depletion. The potential of cyclin A/CDK2 to regulate Chk1 revealed that the inhibitory phosphorylations, Ser286 and Ser301, were not directly catalysed by cyclin A/CDK2 in G2 phase to regulate mitotic entry. It appeared that the ability of cyclin A/CDK2 to regulate cyclin B/CDK1 activation impacted cyclin B/CDK1s phosphorylation of Chk1 on Ser286 and Ser301, thereby contributing to the delay in G2/M phase progression. Chk1 inhibition/depletion partially abrogated the cyclin A/CDK2 dependent G2 delay, and was less effective in abrogating G2 phase checkpoint suggesting that other cyclin A/CDK2 dependent mechanisms contributed to these roles of cyclin A/CDK2. In an attempt to identify these other contributing factors another G2/M phase regulator known to be regulated by cyclin A/CDK2, Cdh1 and its substrates Plk1 and Claspin were examined. Cdh1 levels were reduced in cyclin A/CDK2 depleted/inhibited cells although this had little effect on Plk1, a known Cdh1 substrate. However, the level of another substrate, Claspin, was increased. Cdh1 depletion mimicked the effect of cyclin A depletion but to a weaker extent and was sufficient at increasing Claspin levels similar to the increase caused by cyclin A depletion. Co-depletion of cyclin A and Claspin blocked the accumulation of activated Chk1 normally seen with cyclin A depletion alone. However Claspin depletion alone did not reduce the cyclin A/CDK2 dependent G2 delay but this is likely to be a result of inhibition of S phase roles of Claspin. Together, these data suggest that cyclin A/CDK2 regulates a number of different mechanisms that contribute to G2/M phase progression. Here it has been demonstrated that in normal G2/M progression and possibly to a lesser extent in G2 phase checkpoint recovery, cyclin A/CDK2 regulates the level of Cdh1 which in turn affects at least one of its substrates, Claspin, and consequently results in the increased level of activated Chk1 observed. However, the involvement of Cdh1 and Claspin alone does not explain the G2 phase delay observed with cyclin A/CDK2 depletion/inhibition. It is likely that other mechanisms, possibly including cyclin A/CDK2 regulation of Wee1 and FoxM1, as reported by others, combine with the mechanism described here to regulate normal G2/M phase progression and G2 phase checkpoint recovery. These findings support the critical role for cyclin A/CDK2 in regulating progression into mitosis and suggest that upstream regulators of cyclin A/CDK2 activation will also be critical controllers of this cell cycle transition. The pathways that work to co-ordinate cell cycle progression are very intricate and deciphering these pathways, required for normal cell cycle progression, is key to understanding tumour development. By understanding cell cycle regulatory pathways it will allow the identification of the pathway/s and their mechanism/s that become affected in tumourgenesis. This will lead to the development of better targeted therapies, inferring better efficacy with fewer side effects than commonly seen with the use of traditional therapies, such as chemotherapy. Furthermore, this has the potential to positively impact the development of personalised medicines and the customisation of healthcare.

A method of switch selection for an electric vehicle drive

The key to reducing cost of electric vehicles is integration. All too often systems such as the motor, motor controller, batteries and vehicle chassis/body are considered as separate problems. The truth is that a lot of trade-offs can be made between these systems, causing an overall improvement in many areas including total cost. Motor controller and battery cost have a relatively simple relationship; the less energy lost in the motor controller the less energy that has to be carried in the batteries, hence the lower the battery cost. A motor controller’s cost is primarily influenced by the cost of the switches. This paper will therefore present a method of assessing the optimal switch selection on the premise that the optimal switch is the one that produces the lowest system cost, where system cost is the cost of batteries + switches.