A critique of the depressed industry theory.

Thesis (M.A.)--Boston Universit

Integrating ecology and economics in the mathematical modelling of marine ecosystems

This thesis focusses on the integration of economics and ecology in the mathematical modelling of marine ecosystems. The project addressed two aspects of the problem, 1) the relationship between fish price and landings, and 2) the formulation and solving a mean field game model for fisheries. Regarding price flexibility, we performed statistical analysis on ex-vessel fish prices, landings, and other market variables for the whole UK market, and estimated negative own-price flexibilities for numerous individual fish species, and for some broadly defined guilds of species. These provided relationships between the quantity landed and the price received, which generates a feedback between the marine ecosystem and human activity. Regarding mean field games, we developed a model which considers an economic game with a large number of players exploiting a common resource, whose payoffs depend on the collective the actions of all other players. The application of mean field game approaches to a common resource situation was novel and absent in the literature. Solving the mean field game model numerically, we were able to dynamically simulate the feedback between the marine ecosystem and fishing activity. This allowed us to investigate how the dynamics of the coupled economic-ecological system depended on ecological and economic factors, including the price flexibility identified earlier. We found interesting results relating to the impact of price flexibility and its interaction with stock growth rate, showing that higher price flexibilities resulted in increased fishing pressure for stocks with lower growth rates, but decreased fishing pressure for stocks with very high growth rates. Finally, we modelled the implementation of regulations in the mean field game, and demonstrated how these regulations affect the distribution of fishing activity in a mean field game model for a North Sea cod fishery.This thesis focusses on the integration of economics and ecology in the mathematical modelling of marine ecosystems. The project addressed two aspects of the problem, 1) the relationship between fish price and landings, and 2) the formulation and solving a mean field game model for fisheries. Regarding price flexibility, we performed statistical analysis on ex-vessel fish prices, landings, and other market variables for the whole UK market, and estimated negative own-price flexibilities for numerous individual fish species, and for some broadly defined guilds of species. These provided relationships between the quantity landed and the price received, which generates a feedback between the marine ecosystem and human activity. Regarding mean field games, we developed a model which considers an economic game with a large number of players exploiting a common resource, whose payoffs depend on the collective the actions of all other players. The application of mean field game approaches to a common resource situation was novel and absent in the literature. Solving the mean field game model numerically, we were able to dynamically simulate the feedback between the marine ecosystem and fishing activity. This allowed us to investigate how the dynamics of the coupled economic-ecological system depended on ecological and economic factors, including the price flexibility identified earlier. We found interesting results relating to the impact of price flexibility and its interaction with stock growth rate, showing that higher price flexibilities resulted in increased fishing pressure for stocks with lower growth rates, but decreased fishing pressure for stocks with very high growth rates. Finally, we modelled the implementation of regulations in the mean field game, and demonstrated how these regulations affect the distribution of fishing activity in a mean field game model for a North Sea cod fishery

Footprinting and Circular Dichroism Studies on Paromomycin Binding to the Packaging Region of Human Immunodeficiency Virus Type-1

We have studied the interaction of the aminoglycoside drug, paromomycin, with a 171-mer from the packaging region of HIV-1 (ψ-RNA), using quantitative footprinting and circular dichroism spectroscopy. The footprinting autoradiographic data were obtained by cutting end-labeled RNA with RNase I or RNase T1 in the presence of varying paromomycin concentrations. Scanning the autoradiograms produced footprinting plots showing cleavage intensities for specific sites on the ψ-RNA as functions of drug concentration. Footprinting plots showing binding were analyzed using a two-state model to give apparent binding constants for specific sites of the ψ-RNA. These plots show that the highest-affinity paromomycin binding site involves nucleotides near bulges in the main stem and SL-1, and other nucleotides in SL-4 of the ψ-RNA. RNase I gives an apparent value of K for this drug site of ∼1.7×105 M−1 while RNase T1 reports a value of K of ∼8×104 M−1 (10 mM Tris HCl, pH 7). Footprinting shows that loading the highest affinity site with paromomycin causes structural changes in the single-stranded linker regions, between the stem-loops and main stem and the loops of SL-1 and SL-3. Drug-induced structural changes also affect the intensity of the 208 nm band in the circular dichroism spectrum of the ψ-RNA. Fitting the changes in CD band intensity to a two-state model yielded a binding constant for the highest-affinity drug site of 6×106 M−1. Thus, the binding constants from footprinting are lower than those obtained for the highest-affinity site from the circular dichroism spectrum, and lower than those earlier obtained using absorption spectroscopy (Sullivan, J. M.; Goodisman, J.; Dabrowiak, J. C., Bioorg. Med. Chem. Lett. 2002, 12, 615). The discrepancy may be due to competitive binding between drug and cleavage agent in the footprinting experiments, but other explanations are discussed. In addition to revealing sites of binding and regions of drug-induced structural change, footprinting showed that the loop regions of SL-1, SL-3 and SL-4 are exposed in the RNA, whereas the linker region between SL-1 and SL-2 is ‘buried’ and not accessible to cutting by RNase I or RNase T1

On a mean field game formulation of fish stock exploitation

[Abstract unavailable

Monomer-Dimer Equilibrium Constants of RNA in the Dimer Initiation Site of Human Immunodeficiency Virus Type 1

The genome of the human immunodeficiency virus (HIV) exists as a dimer of two identical RNA molecules hydrogen bonded to each other near their 5\u27 ends. The dimer, known to be important for viral infectivity, is formed by two monomers interacting through a stem-loop structure called the dimer initiation site (DIS). An initially formed intermediate, the kissing dimer, is unstable and rearranges to the stable, duplex form. In this report we use nondenaturing polyacrylamide gel electrophoresis to measure the monomer-dimer equilibrium constant of three RNA sequences, 41-, 27-, and 19-mers, located in the DIS of the MAL isolate of HIV-1. Experiments in which the RNA was equilibrated at various temperatures before electrophoresis revealed that interconversion is rapid for all the sequences, so that they reach equilibrium in the loading well of the gel at 5 degrees C before they enter the gel proper. However, interconversion kinetics in the gel are slow, so autoradiographic spot intensities can be used to measure the amounts of monomer and dimer present when the sample entered the gel. After correction for the amount of RNA added with the radiolabel and dilution of samples in the loading well of the gel, dimerization equilibrium constants were calculated from spot intensities. The calculated values of the dimerization constant K at 5 degrees C were approximately 10(5), approximately 10(6), and approximately 10(8) M(-1) for the 41-, 27-, and 19-mers, respectively, in solutions of ionic strength, I, of about 100 mM. The decrease in K by three orders of magnitude between the 19-mer and 41-mer is due in part to the change in rotational entropy of rodlike molecules on dimerization and in part to the increased conformational entropy of the monomers. As expected, increased ionic strength increases the dimerization constant for all three RNAs. For the 41-mer, however, K has a maximum value at I approximately 140 mM. The origin of the decrease in K for higher I is unknown but it may be due to formation of species (perhaps higher order oligomers) that do not enter the gel. The 41-mer exists in two dimeric forms assigned to the kissing and duplex dimers. The ratio of kissing to duplex form at 5 degrees C is 0.48 +/- 0.22 at I = 113 mM and 0.91 +/- 0.35 at I = 183 mM. The observed decrease in K with RNA length suggests that the dimerization constant of the packaging region of HIV-1 is small, \u3c approximately 10(5) M(-1), implying that the nucleocapsid protein is important in promoting dimerization in the capsid of the virus

Acyclic Identification of Aptamers for Human alpha-Thrombin Using Over-Represented Libraries and Deep Sequencing

BACKGROUND: Aptamers are oligonucleotides that bind proteins and other targets with high affinity and selectivity. Twenty years ago elements of natural selection were adapted to in vitro selection in order to distinguish aptamers among randomized sequence libraries. The primary bottleneck in traditional aptamer discovery is multiple cycles of in vitro evolution. METHODOLOGY/PRINCIPAL FINDINGS: We show that over-representation of sequences in aptamer libraries and deep sequencing enables acyclic identification of aptamers. We demonstrated this by isolating a known family of aptamers for human α-thrombin. Aptamers were found within a library containing an average of 56,000 copies of each possible randomized 15mer segment. The high affinity sequences were counted many times above the background in 2-6 million reads. Clustering analysis of sequences with more than 10 counts distinguished two sequence motifs with candidates at high abundance. Motif I contained the previously observed consensus 15mer, Thb1 (46,000 counts), and related variants with mostly G/T substitutions; secondary analysis showed that affinity for thrombin correlated with abundance (K(d) = 12 nM for Thb1). The signal-to-noise ratio for this experiment was roughly 10,000∶1 for Thb1. Motif II was unrelated to Thb1 with the leading candidate (29,000 counts) being a novel aptamer against hexose sugars in the storage and elution buffers for Concanavilin A (K(d) = 0.5 µM for α-methyl-mannoside); ConA was used to immobilize α-thrombin. CONCLUSIONS/SIGNIFICANCE: Over-representation together with deep sequencing can dramatically shorten the discovery process, distinguish aptamers having a wide range of affinity for the target, allow an exhaustive search of the sequence space within a simplified library, reduce the quantity of the target required, eliminate cycling artifacts, and should allow multiplexing of sequencing experiments and targets

Binding of aminoglycoside antibiotics to helix 69 of 23S rRNA

Aminoglycosides antibiotics negate dissociation and recycling of the bacterial ribosome’s subunits by binding to Helix 69 (H69) of 23S rRNA. The differential binding of various aminoglycosides to the chemically synthesized terminal domains of the Escherichia coli and human H69 has been characterized using spectroscopy, calorimetry and NMR. The unmodified E. coli H69 hairpin exhibited a significantly higher affinity for neomycin B and tobramycin than for paromomycin (Kds = 0.3 ± 0.1, 0.2 ± 0.2 and 5.4 ± 1.1 µM, respectively). The binding of streptomycin was too weak to assess. In contrast to the E. coli H69, the human 28S rRNA H69 had a considerable decrease in affinity for the antibiotics, an important validation of the bacterial target. The three conserved pseudouridine modifications (Ψ1911, Ψ1915, Ψ1917) occurring in the loop of the E. coli H69 affected the dissociation constant, but not the stoichiometry for the binding of paromomycin (Kd = 2.6 ± 0.1 µM). G1906 and G1921, observed by NMR spectrometry, figured predominantly in the aminoglycoside binding to H69. The higher affinity of the E. coli H69 for neomycin B and tobramycin, as compared to paromomycin and streptomycin, indicates differences in the efficacy of the aminoglycosides