Hawthorn Crater Project Report 1

This project report and presentation outline the research outcomes from the first field study at Hawthorn Ridge Crater at Beaumont Hamel in France. It is co edited by Associate Professor Fiona Graham and Professor John Cassella. Authors include both academic partner Keele University and industry partners including Stoke on Trent City Council, UAV Dynamics, and FARO and analyse the findings relating to the inter disciplinary project including: film, forensic science, history, and archaeology. The crater is one of the largest in France, blown to mark the beginning of the Battle of the Somme on July 1st 1916. Exclusive access has been given to the site for research. The site is of particular significance to film history marking one of the first examples of battlefield film by Geoffrey Malins

Outreach Strategies to Recruit Low-Income African American Men to Participate in Health Promotion Programs and Research: Lessons From the Men of Color Health Awareness (MOCHA) Project

African American men continue to bear a disproportionate share of the burden of disease. Engaging these men in health research and health promotion programs—especially lower-income, African American men who are vulnerable to chronic disease conditions such as obesity and heart disease—has historically proven quite difficult for researchers and public health practitioners. The few effective outreach strategies identified in the literature to date are largely limited to recruiting through hospital clinics, churches, and barbershops. The Men of Color Health Awareness (MOCHA) project is a grassroots, community-driven initiative that has developed a number of innovative outreach strategies. After describing these strategies, we present data on the demographic and health characteristics of the population reached using these methods, which indicate that MOCHA has been highly effective in reaching this population of men

Stock Market Speculation: Spontaneous Symmetry Breaking of Economic Valuation

Firm foundation theory estimates a security's firm fundamental value based on four determinants: expected growth rate, expected dividend payout, the market interest rate and the degree of risk. In contrast, other views of decision-making in the stock market, using alternatives such as human psychology and behavior, bounded rationality, agent-based modeling and evolutionary game theory, expound that speculative and crowd behavior of investors may play a major role in shaping market prices. Here, we propose that the two views refer to two classes of companies connected through a ``phase transition''. Our theory is based on 1) the identification of the fundamental parity symmetry of prices ($p \to -p$), which results from the relative direction of payment flux compared to commodity flux and 2) the observation that a company's risk-adjusted growth rate discounted by the market interest rate behaves as a control parameter for the observable price. We find a critical value of this control parameter at which a spontaneous symmetry-breaking of prices occurs, leading to a spontaneous valuation in absence of earnings, similarly to the emergence of a spontaneous magnetization in Ising models in absence of a magnetic field. The low growth rate phase is described by the firm foundation theory while the large growth rate phase is the regime of speculation and crowd behavior. In practice, while large ``finite-time horizon'' effects round off the predicted singularities, our symmetry-breaking speculation theory accounts for the apparent over-pricing and the high volatility of fast growing companies on the stock markets.Comment: 23 pages, 10 figure

Temporal profiling of the cortical synaptic mitochondrial proteome identifies ageing associated regulators of stability

Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo

What drives security issuance decisions: Market timing, pecking order, or both?

We study market timing and pecking order in a sample of debt and equity issues and share repurchases of Canadian firms from 1998 to 2007. We find that only when firms are not financially constrained is there evidence that firms issue (repurchase) equity when their shares are overvalued (undervalued) and evidence that overvalued issuers earn lower postannouncement long-run returns. Similarly, we find that only when firms are not overvalued do they prefer debt to equity financing. These findings highlight an interaction between market timing and pecking order effects

Prophylactic Β-blocker therapy: Clinical implications of an aggregate analysis

Background. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. Methods. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. Results. After two years, the mean (± SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 ± 3 percent in the beta-adrenergic-antagonist treatment group and 65 ± 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 ± 2 percent in the treatment group and 82 ± 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 ± 3 percent in the treatment group and 68 ± 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 ± 3 percent in the treatment group and 53 ± 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P < 0.001) and death (P < 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P < 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. Conclusions. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38371/1/1840150229_ftp.pd

A bioluminescent microbial biosensor for in vitro pretreatment assessment of cytarabine efficacy in leukemia

BACKGROUND: The nucleoside analog cytarabine (Ara-C [cytosine arabinoside]) is the key agent for treating acute myeloid leukemia (AML); however, up to 30% of patients fail to respond to treatment. Screening of patient blood samples to determine drug response before commencement of treatment is needed. This project aimed to construct and evaluate a self-bioluminescent reporter strain of Escherichia coli for use as an Ara-C biosensor and to design an in vitro assay to predict Ara-C response in clinical samples. METHODS: Weused transposition mutagenesis to create a cytidine deaminase (cdd)-deficient mutant of E. coli MG1655 that responded to Ara-C. The strain was transformed with the luxCDABE operon and used as a whole-cell biosensor for development an 8-h assay to determine Ara-C uptake and phosphorylation by leukemic cells. RESULTS: Intracellular concentrations of 0.025 μmol/L phosphorylated Ara-C were detected by significantly increased light output (P < 0.05) from the bacterial biosensor. Results using AML cell lines with known response to Ara-C showed close correlation between the 8-h assay and a 3-day cytotoxicity test for Ara-C cell killing. In retrospective tests with 24 clinical samples of bone marrow or peripheral blood, the biosensor-based assay predicted leukemic cell response to Ara-C within 8 h. CONCLUSIONS: The biosensor-based assay may offer a predictor for evaluating the sensitivity of leukemic cells to Ara-C before patients undergo chemotherapy and allow customized treatment of drug-sensitive patients with reduced Ara-C dose levels. The 8-h assay monitors intracellular Ara-CTP (cytosine arabinoside triphosphate) levels and, if fully validated, may be suitable for use in clinical settings. © 2010 American Association for Clinical Chemistry

The mitochondrial protein Sideroflexin 3 (SFXN3) influences neurodegeneration pathways in vivo

Synapses are a primary pathological target in neurodegenerative diseases. Identifying therapeutic targets at the synapse could delay progression of numerous conditions. The mitochondrial protein SFXN3 is a neuronally-enriched protein expressed in synaptic terminals and regulated by key synaptic proteins, including α-synuclein. We first show that SFXN3 uses the carrier import pathway to insert into the inner mitochondrial membrane. Using high-resolution proteomics on Sfxn3-KO mice synapses, we then demonstrate that SFXN3 influences proteins and pathways associated with neurodegeneration and cell death (including CSPα and Caspase-3), as well as neurological conditions (including Parkinson’s disease and Alzheimer’s disease). Over-expression of SFXN3 orthologues in Drosophila models of Parkinson’s Disease significantly reduced dopaminergic neuron loss. In contrast, the loss of SFXN3 was insufficient to trigger neurodegeneration in mice, indicating an anti- rather than pro-neurodegeneration role for SFXN3. Taken together, these results suggest a potential role for SFXN3 in the regulation of neurodegeneration pathways

Critical Market Crashes

This review is a partial synthesis of the book ``Why stock market crash'' (Princeton University Press, January 2003), which presents a general theory of financial crashes and of stock market instabilities that his co-workers and the author have developed over the past seven years. The study of the frequency distribution of drawdowns, or runs of successive losses shows that large financial crashes are ``outliers'': they form a class of their own as can be seen from their statistical signatures. If large financial crashes are ``outliers'', they are special and thus require a special explanation, a specific model, a theory of their own. In addition, their special properties may perhaps be used for their prediction. The main mechanisms leading to positive feedbacks, i.e., self-reinforcement, such as imitative behavior and herding between investors are reviewed with many references provided to the relevant literature outside the confine of Physics. Positive feedbacks provide the fuel for the development of speculative bubbles, preparing the instability for a major crash. We demonstrate several detailed mathematical models of speculative bubbles and crashes. The most important message is the discovery of robust and universal signatures of the approach to crashes. These precursory patterns have been documented for essentially all crashes on developed as well as emergent stock markets, on currency markets, on company stocks, and so on. The concept of an ``anti-bubble'' is also summarized, with two forward predictions on the Japanese stock market starting in 1999 and on the USA stock market still running. We conclude by presenting our view of the organization of financial markets.Comment: Latex 89 pages and 38 figures, in press in Physics Report