Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.

On the applicability of mathematics : philosophical and historical perspectives

The present thesis is a contribution to the debate on the applicability of mathematics; it examines the interplay between mathematics and the world, using historical case studies. The first part of the thesis consists of four small case studies. In chapter 1, I criticize "ante rem structuralism", proposed by Stewart Shapiro, by showing that his so-called "finite cardinal structures" are in conflict with mathematical practice. In chapter 2, I discuss Leonhard Euler's solution to the Königsberg bridges problem. I propose interpreting Euler's solution both as an explanation within mathematics and as a scientific explanation. I put the insights from the historical case to work against recent philosophical accounts of the Königsberg case. In chapter 3, I analyze the predator-prey model, proposed by Lotka and Volterra. I extract some interesting philosophical lessons from Volterra's original account of the model, such as: Volterra's remarks on mathematical methodology; the relation between mathematics and idealization in the construction of the model; some relevant details in the derivation of the Third Law, and; notions of intervention that are motivated by one of Volterra's main mathematical tools, phase spaces. In chapter 4, I discuss scientific and mathematical attempts to explain the structure of the bee's honeycomb. In the first part, I discuss a candidate explanation, based on the mathematical Honeycomb Conjecture, presented in Lyon and Colyvan (2008). I argue that this explanation is not scientifically adequate. In the second part, I discuss other mathematical, physical and biological studies that could contribute to an explanation of the bee's honeycomb. The upshot is that most of the relevant mathematics is not yet sufficiently understood, and there is also an ongoing debate as to the biological details of the construction of the bee's honeycomb. The second part of the thesis is a bigger case study from physics: the genesis of GR. Chapter 5 is a short introduction to the history, physics and mathematics that is relevant to the genesis of general relativity (GR). Chapter 6 discusses the historical question as to what Marcel Grossmann contributed to the genesis of GR. I will examine the so-called "Entwurf" paper, an important joint publication by Einstein and Grossmann, containing the first tensorial formulation of GR. By comparing Grossmann's part with the mathematical theories he used, we can gain a better understanding of what is involved in the first steps of assimilating a mathematical theory to a physical question. In chapter 7, I introduce, and discuss, a recent account of the applicability of mathematics to the world, the Inferential Conception (IC), proposed by Bueno and Colyvan (2011). I give a short exposition of the IC, offer some critical remarks on the account, discuss potential philosophical objections, and I propose some extensions of the IC. In chapter 8, I put the Inferential Conception (IC) to work in the historical case study: the genesis of GR. I analyze three historical episodes, using the conceptual apparatus provided by the IC. In episode one, I investigate how the starting point of the application process, the "assumed structure", is chosen. Then I analyze two small application cycles that led to revisions of the initial assumed structure. In episode two, I examine how the application of "new" mathematics - the application of the Absolute Differential Calculus (ADC) to gravitational theory - meshes with the IC. In episode three, I take a closer look at two of Einstein's failed attempts to find a suitable differential operator for the field equations, and apply the conceptual tools provided by the IC so as to better understand why he erroneously rejected both the Ricci tensor and the November tensor in the Zurich Notebook.

Are there two species of Pygmy Shrews (Sorex)? Revisiting the question using DNA sequence data

Pygmy Shrews in North America have variously been considered to be one species (Sorex hoyi) or two species (S. hoyi and S. thompsoni). Currently, only S. hoyi is recognized. In this study, we examine mitochondrial DNA sequence data for the cytochrome b gene to evaluate the level of differentiation and phylogeographic relationships among eleven samples of Pygmy Shrews from across Canada. Pygmy Shrews from eastern Canada (i.e., Ontario, Quebec, New Brunswick, Nova Scotia, and Prince Edward Island) are distinct from Pygmy Shrews from western Canada (Alberta, Yukon) and Alaska. The average level of sequence divergence between these clades (3.3%) falls within the range of values for other recognized pairs of sister species of shrews. A molecular clock based on third position transversion substitutions suggests that these two lineages diverged between 0.44 and 1.67 million years ago. These molecular phylogenetic data. combined with a reinterpretation of previously published morphological data, are suggestive of separate species status for S. hoyi and S. thompsoni as has been previously argued by others. Further analysis of specimens from geographically intermediate areas (e.g., Manitoba. northern Ontario) is required to determine if there is secondary contact and/or introgression between these two putative species.

Is the consumption-income ratio stationary? Evidence from linear and nonlinear panel unit root tests for OECD and non-OECD countries

This paper applies recently developed heterogeneous nonlinear and linear panel unit root tests that account for cross-sectional dependence to 24 OECD and 33 non-OECD countries’ consumption-income ratios over the period 1951–2003. We apply a recently developed methodology that facilitates the use of panel tests to identify which individual cross-sectional units are stationary and which are nonstationary. This extends evidence provided in the recent literature to consider both linear and nonlinear adjustment in panel unit root tests, to address the issue of cross-sectional dependence, and to substantially expand both time-series and cross sectional dimensions of the data analysed. We find that the majority (65%) of the series are nonstationary with slightly fewer OECD countries’ (61%) series exhibiting a unit root than non-OECD countries (68%).

Does Public Governance Always Matter? How Experience of Poor Institutional Quality Influences FDI to the South

This paper investigates whether the higher prevalence of South multinational enterprises (MNEs) in risky developing countries may be explained by the experience that they have acquired of poor institutional quality at home. We confirm the intuition provided by our analytical model by empirically showing that the positive impact of good public governance on foreign direct investment (FDI) in a given host country is moderated significantly, and even in some cases eliminated, when MNEs have been faced with poor institutional quality at home.

Policy Shocks and Contract Renegotiation: Who Gets Raked Over the Coals?

Changes in climate policy have large influence on businesses. Firms anticipate and respond to such changes, but what if they have already engaged in a longterm relationship with other firms or customers at the time of policy change? For example, coal supply to power stations is typically based on long-term contracts, while the nature of the buyer-supplier relationship may well be affected substantially by climate regulations. However, there has been little evidence on whether or how firms amend their contractual agreements in response to a change in policy.

Market Familiarity and the Location of South and North MNEs

We use a systematic empirical analysis of the determinants of South-South (SS) and North-South (NS) foreign direct investment (FDI) as a canvas to explore how multinational enterprises’ (MNEs) location decisions are shaped by better acquaintance with a foreign market resulting from bilateral ties, experience of international expansion, and knowledge of how to deal with poor governance. We find that these various aspects of market familiarity, which can interact together, are important to explain and differentiate the location behaviours of South MNEs (S-MNEs) and North MNEs (N-MNEs) in developing countries.

Institutional Quality and FDI to the South An Analytical Approach

We ask whether MNEs’ experience of institutional quality and political risk within their “home” business environments influences their decisions to enter a given country. We set out an explicit theoretical model that allows for the possibility that firms from South source countries may, by virtue of their experience with poor institutional quality, derive a competitive advantage over firms from North countries with respect to investing in destinations in the South. We show that the experience gained by such MNEs of poorer institutional environments may result in their being more prepared to invest in other countries with correspondingly weak institutions.

Rebellion against Reason? A Study of Expressive Choice and Strikes

In this paper we challenge the conventional view that strikes are caused by asymmetric information regarding rm profitability such that union members are uninformed. Instead, we build an expressive model of strikes where the perception of unfairness provides the expressive benefi t of voting for a strike. The model predicts that larger union size increases both wage offers and the incidence of strikes. Furthermore, while asymmetric information is still important in causing strikes, we find that it is the employer who is not fully informed about the level of emotionality within the union, thereby contributing to strike incidence. An empirical test using UK data provides support for the predictions. In particular, union size has a positive effect on the incidence of strikes and other industrial actions even when asymmetric information regarding profitability is controlled for.

Rebellion against Reason? A Study of Expressive Choice and Strikes

In this paper we challenge the conventional view that strikes are caused by asymmetric information regarding firm protability such that union members are uninformed. Instead, we build an expressive model of strikes where the perception of unfairness provides the expressive benefit of voting for a strike. The model predicts that larger union size increases both wage offers and the incidence of strikes. Furthermore, while asymmetric information is still important in causing strikes, we find that it is the employer who is not fully informed about the level of emotionality within the union, thereby contributing to strike incidence. An empirical test using UK data provides support for the predictions. In particular, union size has a positive effect on the incidence of strikes and other industrial actions even when asymmetric information regarding protability is controlled for.

No Good Deals - No Bad Models

Faced with the problem of pricing complex contingent claims, an investor seeks to make his valuations robust to model uncertainty. We construct a notion of a model- uncertainty-induced utility function and show that model uncertainty increases the investor's eff ective risk aversion. Using the model-uncertainty-induced utility function, we extend the \No Good Deals" methodology of Cochrane and Sa a-Requejo [2000] to compute lower and upper good deal bounds in the presence of model uncertainty. We illustrate the methodology using some numerical examples.

FDI, Trade Costs and Regional Asymmetries

We set up a trade model where three countries compete for an exogenous number of firms. Our innovation lies in the geography of the model. Of the three countries, one is the hub through which all trade takes place. First, we establish the natural geography of the region, which is given by the equilibrium distribution of industrial activity in the absence of taxes or subsidies. We then examine the implications for corporate taxes when the countries compete with each other to attract firms. We find that, even when all countries are the same size, the centrality of the hub gives it an advantage in tax setting, such that its equilibrium tax can be larger than that of the spokes and yet it still attracts a disproportionate share of industry. Thus geographic advantage in tax competition has a second dimension, centrality in addition to size.

Policy Labels and Investment Decision-making

Much attention in recent years has turned to the potential of behavioural insights to improve the performance of government policy. One behavioural concept of interest is the effect of a cash transfer label on how the transfer is spent. The Winter Fuel Payment (WFP) is a labelled cash transfer to offset the costs of keeping older households warm in the winter. Previous research has shown that households spend a higher proportion of the WFP on energy expenditures due to its label (Beatty et al., 2011). If households interpret the WFP as money for their energy bills, it may reduce their willingness to undertake investments which help achieving the same goal, such as the adoption of renewable energy technologies. In this paper we show that the WFP has distortionary effects on the renewable technology market. Using the sharp eligibility criteria of the WFP in a Regression Discontinuity Design, this analysis finds a reduction in the propensity to install renewable energy technologies of around 2.7 percentage points due to the WFP. This is a considerable number. It implies that 62% of households (whose oldest member turns 60) would have invested in renewable energy but refrain to do so after receiving the WFP. This analysis suggests that the labelling effect spreads to products related to the labelled good. In this case, households use too much energy from sources which generate pollution and too little from relatively cleaner technologies.

Preliminary laboratory and field trials of a heated pheromone trap for the sandfly lutzomyia logipalpis (Diptera: Psychodidae)

A heated pheromone trap for the sandfly Lutzomyia longipalpis was tested in the laboratory using filter paper or plastic vial dispensers. Male pheromone extracted from 8 male tergal glands and absorbed on to filter paper dispensers attracted 82/120 (68.3%) of virgin females released in cages. Similarly plastic vial dispensers baited with the extract of 24 males caught 73/120 (61%). In field trials carried out near januária, Minas Gerais, Brazil using the plastic dispensers baited with extracts of 50 male tergal glands only 70 female L. longipalpis were captured. Over 1000 male flies were, however, caught during 6 nights, with greater numbers in the unbaited control traps than in the pheromone baited test traps. It is concluded that at excessive concentrations male L. longipalpis pheromone may act as a repellent to conspecific males.

Estimating the Price of ROCs

The UK government introduced the Renewable Obligation (RO), a system of tradable quotas, to encourage the installation of renewable electricity capacity. Each unit of generation from renewables created a renewable obligation certificate (ROC). Electricity generators must either; earn ROCs through their own production, purchase ROCs in the market or pay the buy-out price to comply with the quota set by the RO. A unique aspect of this regulation is that all entities holding ROCs receive a share of the buy-out fund (the sum of all compliance purchases using the buy-out price). This set-up ensures that the difference between the market price for ROCs and the buy-out price should equal the expected share of the buy-out fund, as regulated entities arbitrage these two compliance options. The expected share of the buy-out fund depends on whether enough renewable generation is available to meet the quota. This analysis tests whether variables associated with renewable generation or electricity demand are correlated with, and thus can help predict, the price of ROCs.