Stability of Flat Space to Singular Instantons

Hawking and the author have proposed a class of singular, finite action instantons for defining the initial conditions for inflation. Vilenkin has argued they are unacceptable. He exhibited an analogous class of asymptotically flat instantons which on the face of it lead to an instability of Minkowski space. However, all these instantons must be defined by introducing a constraint into the path integral, which is then integrated over. I show that with a careful definition these instantons do not possess a negative mode. Infinite flat space is therefore stable against decay via singular instantons.Comment: 9 pages, RevTex file, including two postscript figure files. Minor typos corrected, figure improve

Looking back at Social Knowledge in the Making

Sociolog

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment

Background: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. Results: We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. Conclusions: This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers

Inactivation of mammalian Ero 1α is catalysed by specific protein disulfide isomerases

Disulfide formation within the endoplasmic reticulum is a complex process requiring a disulfide exchange protein such as protein disulfide isomerase and a mechanism to form disulfides de novo. In mammalian cells, the major pathway for de novo disulfide formation involves the enzyme Ero1α which couples oxidation of thiols to the reduction of molecular oxygen to form hydrogen peroxide. Ero1α activity is tightly regulated by a mechanism that requires the formation of regulatory disulfides. These regulatory disulfides are reduced to activate and reform to inactive the enzyme. To investigate the mechanism of inactivation we analysed regulatory disulfide formation in the presence of various oxidants under controlled oxygen concentration. Neither molecular oxygen, nor hydrogen peroxide was able to oxidise Ero1α efficiently to form the correct regulatory disulfides. However, specific members of the PDI family such as PDI or ERp46 were able to catalyse this process. Further studies showed that both active sites of PDI contribute to the formation of regulatory disulfides in Ero1α and that the PDI substrate binding domain is crucial to allow electron transfer between the two enzymes. These results demonstrate a simple feedback mechanism of regulation of mammalian Ero1α involving its primary substrate

Exact holomorphic differentials on a quotient of the Ree curve

We produce several families of exact holomorphic differentials on a quotient X of the Ree curve in characteristic 3, defined by X:yq-y=xq0(xq-x)/Fq (where q0 = 3s, s ≥ 1 and q=3q02). We conjecture that they span the whole space of exact holomorphic differentials, and prove this in the cases s = 1 and s = 2, by calculating the kernel of the Cartier operator

Kahler spinning particles

We construct the U(N) spinning particle theories, which describe particles moving on Kahler spaces. These particles have the same relation to the N=2 string as usual spinning particles have to the NSR string. We find the restrictions on the target space of the theories coming from supersymmetry and from global anomalies. Finally, we show that the partition functions of the theories agree with what is expected from their spectra, unlike that of the N=2 string in which there is an anomalous dependence on the proper time.Comment: References added. 16 Pages (LaTeX

Optimal combinations of imperfect objects

We address the question of how to make best use of imperfect objects, such as defective analog and digital components. We show that perfect, or near-perfect, devices can be constructed by taking combinations of such defects. Any remaining objects can be recycled efficiently. In addition to its practical applications, our `defect combination problem' provides a novel generalization of classical optimization problems.Comment: 4 pages, 3 figures, minor change

The Rolling Tachyon as a Matrix Model

We express all correlation functions in timelike boundary Liouville theory as unitary matrix integrals and develop efficient techniques to evaluate these integrals. We compute large classes of correlation functions explicitly, including an infinite number of terms in the boundary state of the rolling tachyon. The matrix integrals arising here also determine the correlation functions of gauge invariant operators in two dimensional Yang-Mills theory, suggesting an equivalence between the rolling tachyon and QCD_2.Comment: 22pages. 3 figures. v2: added reference, fixed minor typo

Rethinking entrenched narratives about protected areas and human wellbeing in the Global South

Attempts to link human development and biodiversity conservation goals remain a constant feature of policy and practice related to protected areas (PAs). Underlying these approaches are narratives that simplify assumptions, shaping how interventions are designed and implemented. We examine evidence for five key narratives: 1) conservation is pro-poor; 2) poverty reduction benefits conservation; 3) compensation neutralises costs of conservation; 4) local participation is good for conservation; 5) secure tenure rights for local communities support effective conservation. Through a mixed-method synthesis combining a review of 100 peer-reviewed papers and 25 expert interviews, we examined if and how each narrative is supported or countered by the evidence. The first three narratives are particularly problematic. PAs can reduce material poverty, but exclusion brings substantial local costs to wellbeing, often felt by the poorest. Poverty reduction will not inevitably deliver on conservation goals and trade-offs are common. Compensation (for damage due to human wildlife conflict, or for opportunity costs), is rarely sufficient or commensurate with costs to wellbeing and experienced injustices. There is more support for narratives 4 and 5 on participation and secure tenure rights, highlighting the importance of redistributing power towards Indigenous Peoples and Local Communities in successful conservation. In light of the proposed expansion of PAs under the post-2020 Global Biodiversity Framework, we outline implications of our review for the enhancement and implementation of global targets in order to proactively integrate social equity into conservation and the accountability of conservation actors