The Challenge of Managing Modern Complex Projects

This paper presents a review of the most significant contributions on the topic of project complexity. It sets this review within the context of the development of project management as a topic receiving increased attention from both academe and practitioners. Following this review, a proposed framework of project complexity is presented alongside a more granular componentry of project complexity derived from work published by the UK's National Audit Office. The proposed framework is then tested via application to a live case study that is proffered as being a case of project complexity. The purpose of the paper is to present a coherent argument for what can be understood to make a project complex with the paper being the first phase in a research project that seeks to understand what expert project practitioners see as making projects complex and how these experts approach the management of such projects

Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay

Background: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents. Methods: In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro. Results: MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents. Conclusion: Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance

Commensurate 4a04a_0 period Charge Density Modulations throughout the Bi2Sr2CaCu2O8+xBi_2Sr_2CaCu_2O_{8+x} Pseudogap Regime

Theories based upon strong real space (r-space) electron electron interactions have long predicted that unidirectional charge density modulations (CDM) with four unit cell (4$a_0$) periodicity should occur in the hole doped cuprate Mott insulator (MI). Experimentally, however, increasing the hole density p is reported to cause the conventionally defined wavevector $Q_A$ of the CDM to evolve continuously as if driven primarily by momentum space (k-space) effects. Here we introduce phase resolved electronic structure visualization for determination of the cuprate CDM wavevector. Remarkably, this new technique reveals a virtually doping independent locking of the local CDM wavevector at $|Q_0|=2\pi/4a_0$ throughout the underdoped phase diagram of the canonical cuprate $Bi_2Sr_2CaCu_2O_8$. These observations have significant fundamental consequences because they are orthogonal to a k-space (Fermi surface) based picture of the cuprate CDM but are consistent with strong coupling r-space based theories. Our findings imply that it is the latter that provide the intrinsic organizational principle for the cuprate CDM state

Machine Learning in Electronic Quantum Matter Imaging Experiments

Essentials of the scientific discovery process have remained largely unchanged for centuries: systematic human observation of natural phenomena is used to form hypotheses that, when validated through experimentation, are generalized into established scientific theory. Today, however, we face major challenges because automated instrumentation and large-scale data acquisition are generating data sets of such volume and complexity as to defy human analysis. Radically different scientific approaches are needed, with machine learning (ML) showing great promise, not least for materials science research. Hence, given recent advances in ML analysis of synthetic data representing electronic quantum matter (EQM), the next challenge is for ML to engage equivalently with experimental data. For example, atomic-scale visualization of EQM yields arrays of complex electronic structure images, that frequently elude effective analyses. Here we report development and training of an array of artificial neural networks (ANN) designed to recognize different types of hypothesized order hidden in EQM image-arrays. These ANNs are used to analyze an experimentally-derived EQM image archive from carrier-doped cuprate Mott insulators. Throughout these noisy and complex data, the ANNs discover the existence of a lattice-commensurate, four-unit-cell periodic, translational-symmetry-breaking EQM state. Further, the ANNs find these phenomena to be unidirectional, revealing a coincident nematic EQM state. Strong-coupling theories of electronic liquid crystals are congruent with all these observations.Comment: 44 pages, 15 figure

Risk Disclosure and Re-establishing Legitimacy in the Event of a Crisis - Did Northern Rock Use Risk Disclosure to Repair Legitimacy after their 2007 Collapse?

Banks are exposed to a wide range of risk in their every day operation and in response to this they have developed various tools and strategies in order to help avoid, measure, or manage these risks. These tools and strategies are not always successful which has lead to several well publicised crises including amongst others the Barings bank collapse, Allfirst fraud, Santander fraud and more recently the collapse of Northern Rock and its subsequent nationalisation. In order for society to permit their operation firms require legitimacy, where by its actions must conform to cultural and social norms (Suchman 1995). Legitimacy and trust are vitally important and central to bank operations (Linsley and Kajuter 2008) therefore society is more likely to hold them to account (Ashforth and Gibbs 1990), meaning that in the occurrence of an legitimacy adverse risk event or crisis a banking organisation must enact strategies in order to repair and re-establish trust. Whilst legitimacy theory and the use of voluntary disclosures as part of a strategy for restoring organisational legitimacy and reputation has received academic attention (Linsley and Kajuter 2008) there has been limited research on banking disclosures (Linsley and Shrives 2006) and even less done on disclosures issued as a response to an adverse risk event or crisis. The only previous study in this area (see Linsley and Kajuter 2008) focused solely on disclosures located in the annual report but in the concluding remarks identified that the annual report is not the only risk disclosure vehicle and that future research should consider looking at disclosures issued through alternative communication methods. This study therefore will be on the use of disclosures in alternative communication methods (as suggested by Linsley and Kajuter (2008)) in the event of an organisational crisis. The research will aim to add to the still evolving academic understanding of the use of risk disclosure, as well as any part it may play in organisational legitimacy repairing strategies. This exploratory research may also help to identify possible new areas for further study. 3 This study will attempt to achieve these aims by comparing and contrasting Northern Rock Plc‘s before and after their spectacular collapse in 2007 to identify any changes in their risk disclosure in press releases, which have been highlighted as a potential candidate for research in past studies (see Lebar 1982) that, as with most others, have focused on disclosures solely in the annual report. The Northern Rock Plc collapse caused by the lack of wholesale market finance resulting from the 2007 subprime crisis was widely reported and caused substantial damage to the banks legitimacy. The study will first compare press release disclosures in the periods before and after the crisis, and if any changes are found then it will attempt to identify whether the changes were part of a strategy formulated to re-legitimise the bank or not. First the chapter comprises a review of the existing risk, risk disclosure and legitimacy theory literature as well as a definition of key concepts and background to Northern Rock and its legitimacy crisis. Secondly, the research methods are explained, hypotheses developed and choice of press releases for the basis of the study is justified. Finally, the results are analysed and finally conclusions are drawn and suggestions for further research are made

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

The political import of deconstruction—Derrida’s limits?: a forum on Jacques Derrida’s specters of Marx after 25 Years, part I

Jacques Derrida delivered the basis of The Specters of Marx: The State of the Debt, the Work of Mourning, & the New International as a plenary address at the conference ‘Whither Marxism?’ hosted by the University of California, Riverside, in 1993. The longer book version was published in French the same year and appeared in English and Portuguese the following year. In the decade after the publication of Specters, Derrida’s analyses provoked a large critical literature and invited both consternation and celebration by figures such as Antonio Negri, Wendy Brown and Frederic Jameson. This forum seeks to stimulate new reflections on Derrida, deconstruction and Specters of Marx by considering how the futures past announced by the book have fared after an eventful quarter century. Maja Zehfuss, Antonio Vázquez-Arroyo and Dan Bulley and Bal Sokhi-Bulley offer sharp, occasionally exasperated, meditations on the political import of deconstruction and the limits of Derrida’s diagnoses in Specters of Marx but also identify possible paths forward for a global politics taking inspiration in Derrida’s work of the 1990s