The demandingness of Nozick’s ‘Lockean’ proviso

Interpreters of Robert Nozick’s political philosophy fall into two broad groups concerning his application of the ‘Lockean proviso’. Some read his argument in an undemanding way: individual instances of ownership which make people worse off than they would have been in a world without any ownership are unjust. Others read the argument in a demanding way: individual instances of ownership which make people worse off than they would have been in a world without that particular ownership are unjust. While I argue that the former reading is correct as an interpretive matter, I suggest that this reading is nonetheless highly demanding. In particular, I argue that it is demanding when it is expanded to include the protection of nonhuman animals; if such beings are right bearers, as more and more academics are beginning to suggest, then there is no nonarbitrary reason to exclude them from the protection of the proviso

Robert Nozick on nonhuman animals : rights, value and the meaning of life

In his chapter, Josh Milburn argues that Robert Nozick considers nonhuman animals in his philosophical writings, but that these discussions are downplayed in animal ethics and Nozick scholarship. This is regrettable, Milburn proposes, as Nozick is far more sympathetic to animal rights than many other libertarians. Milburn thus offers an analysis of Nozick’s animal ethics. Nozick’s arguments concerning vegetarianism and speciesism are considered, and Milburn argues that tensions in Nozick’s political philosophy potentially open the door to animal rights. Whatever their place in his political philosophy, Milburn contends, nonhuman animals find a comfortable home in Nozick’s axiology and ethics, with their value and the significance of our duties towards them affirmed. Milburn concludes that animal ethicists could learn from Nozick’s distinctive arguments and approaches and find an unexpected ally

Interstitial-mediated diffusion in germanium under proton irradiation

We report experiments on the impact of 2.5 MeV proton irradiation on self-diffusion and dopant diffusion in germanium (Ge). Self-diffusion under irradiation reveals an unusual depth independent broadening of the Ge isotope multilayer structure. This behavior and the observed enhanced diffusion of B and retarded diffusion of P demonstrates that an interstitial-mediated diffusion process dominates in Ge under irradiation. This fundamental finding opens up unique ways to suppress vacancy-mediated diffusion in Ge and to solve the donor deactivation problem that hinders the fabrication of Ge-based nanoelectronic devices

Epigenetic silencing of microRNA-203 dysregulates ABL1 expression and drives Helicobacter-associated gastric lymphomagenesis

Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) develops in the chronically inflamed mucosa of patients infected with the bacterial pathogen Helicobacter pylori. Here we use patient material, primary gastric lymphoma cell cultures and a preclinical model of the disease to examine the role of microRNA-mediated post-transcriptional regulation -focusing in particular on miR-203 and its target ABL1- in gastric MALT lymphomagenesis. Microarray-based microRNA expression profiling revealed a strong down-regulation of the putative tumor suppressor microRNA miR-203 in human MALT lymphoma samples, which resulted from extensive promoter hypermethylation of the miR-203 locus and coincided with the dysregulation of the miR-203 target ABL1 in lymphoma biopsies compared to matched adjacent normal material from the same patients. Treatment of lymphoma B-cells with demethylating agents led to increased miR-203 expression and the concomitant down-regulation of ABL1, confirming the epigenetic regulation of this microRNA. Ectopic re-expression of miR-203 by transfection of a human lymphoma cell line or lentiviral transduction of explanted primary MALT lymphoma cells was sufficient to prevent tumor cell proliferation in vitro. Similarly, the treatment of primary MALT lymphoma cells with the ABL inhibitors imatinib and dasatinib prevented tumor cell growth. Finally, we show that the treatment of tumor-bearing mice with imatinib induces MALT lymphoma regression in a preclinical model of the disease, implicating ABL1 in MALT lymphoma progression. In summary, our results show that the transformation from gastritis to MALT lymphoma is epigenetically regulated by miR-203 promoter methylation and identify ABL1 as a novel target for the treatment of this malignancy

Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins

Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arises against a background of chronic inflammation caused by persistent Helicobacter pylori infection. The clinical and histopathological features of the human tumor can be reproduced by Helicobacter infection of BALB/c mice. In this study, we have analyzed the antibody sequences and antigen specificity of a panel of murine and human MALT lymphoma-derived antibodies. We find that a majority of tumors in patients as well as experimentally infected mice are monoclonal. The tumor immunoglobulin heavy chain genes have undergone somatic hypermutation, and approximately half of all tumors show evidence of intraclonal variation and positive and/or negative selective pressure. Recombinantly expressed MALT lymphoma antibodies bind with intermediate affinity to various unrelated self and foreign antigens, including Helicobacter sonicate, IgG, DNA and stomach extract; antigen binding is blocked in a dose-dependent manner in competitive ELISAs. A strong bias towards the use of V(H) gene segments previously linked to auto- and/or polyreactive antibodies in B-cell malignancies or autoimmune pathologies supports the experimental finding of polyreactivity. Our results suggest that MALT lymphoma development may be facilitated by an array of local self and foreign antigens providing direct antigenic stimulation of the tumor cells via their B-cell receptor