Getting Personal — The Intuition of Neutrality Re-interpreted

According to the Intuition of Neutrality, there is a range of wellbeing levels such that adding people with lives at these levels doesn’t make the world either better or worse. As lives in the neutral range can be good for those who live them, this intuition is in conflict with one of the main tenets of welfarism; it creates a disparity between what is good for a person and what is impersonally good. Adding a person with a good life needn’t make the world better. In “Broome and the Intuition of Neutrality” (2009) I suggested, but did not elaborate, a re-interpretation of the neutral range that would remove the problematic disparity. On this re-interpretation, a life at a level within the neutral range is not merely impersonally neutral; it is also neutral in its personal value: neither better nor worse for its owner than non-existence. Nevertheless, among such personally neutral lives, some might still be personally better or worse than others, provided that they are incommensurable in their personal value with non-existence. In this paper, I explore some of the implications of this ‘personalization’ of the Intuition of neutrality. In particular, I discuss its worrisome implications for neutral-range utilitarianism (NRU). While NRU was originally proposed as a way to avoid the Repugnant Conclusion, it turns out this conclusion is re-instated on the new interpretation and, contrary to what was suggested in my 2009-paper, it remains repugnant. A related point is that it no longer holds that all personally good lives must be better for a person than personally neutral lives. Nor that all personally bad lives must be worse than personally neutral lives. While this might seem strange, it should be accepted. As for the worrisome implications of NRU, these implications do not undermine the personalized Neutrality Intuition itself. The latter might well be retained even if NRU is given up.

Role of Complement in Regulating Inflammation Processes in Renal and Prostate Cancers

For decades, the complement system, the central pillar of innate immune response, was recognized as a protective mechanism against cancer cells and the manipulation of complement effector functions in cancer setting offered a great opportunity to improve monoclonal antibody-based cancer immunotherapies. Similarly, cellular senescence, the process of cell cycle arrest that allow DNA and tissue repair has been traditionally thought to be able to suppress tumor progression. However, in recent years, extensive research has identified the complement system and cellular senescence as two main inducers of tumour growth in the context of chronic, persistent inflammation named inflammaging. Here, we discuss the data describing the ambivalent role of senescence in cancer with a particular focus on tumors that are strongly dependent on complement activation and can be understood by a new, senescence-related point of view: prostate cancer and renal cell carcinoma.

Discrepancy of stratified samples from partitions of the unit cube

We extend the notion of jittered sampling to arbitrary partitions and study the discrepancy of the related point sets. Let $${\varvec{\Omega }}=(\Omega _1,\ldots ,\Omega _N)$$ Ω = ( Ω 1 , … , Ω N ) be a partition of $$[0,1]^d$$ [ 0 , 1 ] d and let the ith point in $${{\mathcal {P}}}$$ P be chosen uniformly in the ith set of the partition (and stochastically independent of the other points), $$i=1,\ldots ,N$$ i = 1 , … , N . For the study of such sets we introduce the concept of a uniformly distributed triangular array and compare this notion to related notions in the literature. We prove that the expected $${{{\mathcal {L}}}_p}$$ L p -discrepancy, $${{\mathbb {E}}}{{{\mathcal {L}}}_p}({{\mathcal {P}}}_{\varvec{\Omega }})^p$$ E L p ( P Ω ) p , of a point set $${{\mathcal {P}}}_{\varvec{\Omega }}$$ P Ω generated from any equivolume partition $${\varvec{\Omega }}$$ Ω is always strictly smaller than the expected $${{{\mathcal {L}}}_p}$$ L p -discrepancy of a set of N uniform random samples for $$p>1$$ p > 1 . For fixed N we consider classes of stratified samples based on equivolume partitions of the unit cube into convex sets or into sets with a uniform positive lower bound on their reach. It is shown that these classes contain at least one minimizer of the expected $${{{\mathcal {L}}}_p}$$ L p -discrepancy. We illustrate our results with explicit constructions for small N. In addition, we present a family of partitions that seems to improve the expected discrepancy of Monte Carlo sampling by a factor of 2 for every N.

Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis

Nonribosomal peptide synthetases containing starter condensation domains direct the biosynthesis of nonribosomal lipopeptides, which generally exhibit wide bioactivities. The acyl chain has strong impacts on bioactivity and toxicity, but the lack of an in-depth understanding of starter condensation domain-mediated lipoinitiation limits the bioengineering of NRPSs to obtain novel derivatives with desired acyl chains. Here, we show that the acyl chains of the lipopeptides rhizomide, holrhizin, and glidobactin were modified by engineering the starter condensation domain, suggesting a workable approach to change the acyl chain. Based on the structure of the mutated starter condensation domain of rhizomide biosynthetic enzyme RzmA in complex with octanoyl-CoA and related point mutation experiments, we identify a set of residues responsible for the selectivity of substrate acyl chains and extend the acyl chains from acetyl to palmitoyl. Furthermore, we illustrate three possible conformational states of starter condensation domains during the reaction cycle of the lipoinitiation process. Our studies provide further insights into the mechanism of lipoinitiation and the engineering of nonribosomal peptide synthetases.

Non-local curvature and Gauss–Bonnet cosmologies by Noether symmetries

Non-local gravity cosmologies are considered under the standard of Noether symmetry approach. In particular, we focus on non-local theories whose gravitational actions depend on curvature and Gauss–Bonnet scalar invariants. Specific functional forms of the related point-like Lagrangians are selected by Noether symmetries, and we solve the corresponding field equations finding out exact cosmological solutions.