Review of Animal Rights Without Liberation: Applied Ethics and Human Obligations

This submission is a book review for Alasdair Cochrane\u27s Animal Rights Without Liberation: Applied Ethics and Human Obligation

Cosmological constraints from the convergence 1-point probability distribution

We examine the cosmological information available from the 1-point probability distribution (PDF) of the weak-lensing convergence field, utilizing fast L-PICOLA simulations and a Fisher analysis. We find competitive constraints in the $\Omega_m$-$\sigma_8$ plane from the convergence PDF with $188\ arcmin^2$ pixels compared to the cosmic shear power spectrum with an equivalent number of modes ($\ell < 886$). The convergence PDF also partially breaks the degeneracy cosmic shear exhibits in that parameter space. A joint analysis of the convergence PDF and shear 2-point function also reduces the impact of shape measurement systematics, to which the PDF is less susceptible, and improves the total figure of merit by a factor of $2-3$, depending on the level of systematics. Finally, we present a correction factor necessary for calculating the unbiased Fisher information from finite differences using a limited number of cosmological simulations.Comment: 10 pages, 5 figure

SYNTHESIS AND ANTICANCER ACTION OF NITRIC OXIDE-RELEASING LIPOSOMES

The implementation of nitric oxide (NO)-based therapeutics has been met with formidable challenges relating to NO’s gaseous, reactive nature and difficulties associated with controlled delivery. Although macromolecular vehicles have been developed for applications in NO release, a common limitation associated with these systems is exposure of the NO donor to the surrounding medium, resulting in unintended NO release. To overcome this issue, liposomes were investigated as new vehicles for NO delivery whereby the NO donor is encapsulated within the aqueous core, protected from the external solution by a lipid membrane. Liposomes with encapsulated N-diazeniumdiolate NO donors were first synthesized using a reverse-phase evaporation protocol. Encapsulation efficiencies for several molecular NO donors were in the range of 33–41%. Relative to the unencapsulated (free) NO donor, NO-release half-lives at pH 7.4 were up to 7-times greater upon encapsulation, yet the NO-releasing liposomes still exhibited their unique pH-sensitive release properties. The liposomes retained ~80% of the encapsulated NO concentrations after 3 months of storage at 4°C, indicating excellent stability. In order to determine if the liposomes held merit as therapeutic agents, cytotoxicity against human pancreatic cancer cells were performed that demonstrated the liposomal NO donors required less NO to kill versus the free NO donor (183 μM and 2.4 mM, respectively). The ability to tune NO-release kinetics of these liposomes was further studied. It was possible to vary the NO-release kinetics by altering the encapsulated NO donor molecule or the phospholipid composing the bilayer (independently or in combination). Phospholipid headgroup surface area was determined to be a main factor in controlling NO-release half-lives. As the surface area of the lipid headgroup was decreased from 0.660 nm2 to 0.420 nm2, a concomitant increase in NO-release half-life was also observed. The composition of the lipid bilayer is known to affect in vivo properties, so NO-release kinetics were also measured in serum and whole blood. Half-lives in serum were equivalent to those measured in buffer, while those measured in blood were ~60% faster. An investigation into the cytotoxicity of slow (t1/2 > 72 h) versus fast (t1/2 ~ 2.5 h) NO-releasing liposomes demonstrated how the biological consequences were dependent on the NO-release rate. Fast NO-releasing liposomes yielded consistently higher LD50 values (>230 μM NO), relative their slow-releasing counterparts (<230 μM NO), across 9 different cancer cell lines encompassing 3 different types of cancer (breast, colorectal, and pancreatic). The fast-release system was able to eradicate 50% of the cells much quicker (~36 h vs. 72 h for slow-release system). Flow cytometry studies suggest that this faster killing is due to a more rapid intracellular build-up of NO, which was observed for both the free and encapsulated NO donors. Western blotting revealed that both the slow and fast NO-release systems could induce apoptosis, albeit to different degrees.Doctor of Philosoph

Electrochemical Modulation of Nitric Oxide Release Using Diazeniumdiolated Species

Honors (Bachelor's)ChemistryUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/96648/1/dsuchyta.pd