Soft branes in supersymmetry-breaking backgrounds

We revisit the analysis of effective field theories resulting from non-supersymmetric perturbations to supersymmetric flux compactifications of the type-IIB superstring with an eye towards those resulting from the backreaction of a small number of anti-D3-branes. Independently of the background, we show that the low-energy Lagrangian describing the fluctuations of a stack of probe D3-branes exhibits soft supersymmetry breaking, despite perturbations to marginal operators that were not fully considered in some previous treatments. We take this as an indication that the breaking of supersymmetry by anti-D3-branes or other sources may be spontaneous rather than explicit. In support of this, we consider the action of an anti-D3-brane probing an otherwise supersymmetric configuration and identify a candidate for the corresponding goldstino.Comment: 36+5 pages. References added, minor typos correcte

Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner.

BackgroundRewriting of the epigenome has risen as a promising alternative to gene editing for precision medicine. In nature, epigenetic silencing can result in complete attenuation of target gene expression over multiple mitotic divisions. However, persistent repression has been difficult to achieve in a predictable manner using targeted systems.ResultsHere, we report that persistent epigenetic memory required both a DNA methyltransferase (DNMT3A-dCas9) and a histone methyltransferase (Ezh2-dCas9 or KRAB-dCas9). We demonstrate that the histone methyltransferase requirement can be locus specific. Co-targeting Ezh2-dCas9, but not KRAB-dCas9, with DNMT3A-dCas9 and DNMT3L induced long-term HER2 repression over at least 50 days (approximately 57 cell divisions) and triggered an epigenetic switch to a heterochromatic environment. An increase in H3K27 trimethylation and DNA methylation was stably maintained and accompanied by a sustained loss of H3K27 acetylation. Interestingly, substitution of Ezh2-dCas9 with KRAB-dCas9 enabled long-term repression at some target genes (e.g., SNURF) but not at HER2, at which H3K9me3 and DNA methylation were transiently acquired and subsequently lost. Off-target DNA hypermethylation occurred at many individual CpG sites but rarely at multiple CpGs in a single promoter, consistent with no detectable effect on transcription at the off-target loci tested. Conversely, robust hypermethylation was observed at HER2. We further demonstrated that Ezh2-dCas9 required full-length DNMT3L for maximal activity and that co-targeting DNMT3L was sufficient for persistent repression by Ezh2-dCas9 or KRAB-dCas9.ConclusionsThese data demonstrate that targeting different combinations of histone and DNA methyltransferases is required to achieve maximal repression at different loci. Fine-tuning of targeting tools is a necessity to engineer epigenetic memory at any given locus in any given cell type

New Directions for New Dimensions: From Strings to Neutrinos to Axions to...

In this talk, I discuss recent developments concerning the possibility of large extra spacetime dimensions. After briefly reviewing how such dimensions can lower the fundamental GUT, Planck, and string scales, I then outline how these scenarios lead to a new higher-dimensional seesaw mechanism for generating neutrino oscillations --- perhaps even without neutrino masses. I also discuss how extra dimensions lead to new mechanisms contributing to the ``invisibility'' of the QCD axion. This talk reports on work done in collaboration with Emilian Dudas and Tony Gherghetta.Comment: 12 pages, LaTeX, 4 figures. Invited plenary talk given at PASCOS '99 (held at Lake Tahoe, California, 10-16 December 1999). To appear in the Proceeding

Apollo Soyuz pamphlet No. 7: Biology in zero-G

The effects of weightlessness on small living organisms, and methods for improving biological techniques were investigated in the seven experiments reported in this pamphlet which is intended as a curriculum supplement for secondary schools. Topics include: (1) killfish hatching and orientation; (2) microbial growth and changes in biorhythm; (3) cell separation by electrophoresis; (4) microbial exchange in the space raft; and (5) changes in astronaut immunity during spaceflight. The pamphlet is intended as a curriculum supplement for secondary schools

Enlarging the Parameter Space of Heterotic M-Theory Flux Compactifications to Phenomenological Viability

Heterotic M-Theory is a promising candidate for that corner of M-theory which makes contact with the real world. However, while the theory requires one of its expansion parameters, $\epsilon$, to be perturbatively small, a successful phenomenology requires $\epsilon = {\cal O}(1)$. We show that the constraint to have small $\epsilon$ is actually unnecessary: instead of the original flux compactification background valid to linear order in $\epsilon$ one has to use its appropriate non-linear extension, the exact background solution. The exact background is determined by supersymmetry and consequently one expects the tree-level cosmological constant to vanish which we demonstrate in detail, thereby verifying once more the consistency of this background. Furthermore we show that the exact background represents precisely the 11d origin of the 5d domain wall solution which is an exact solution of the effective 5d heterotic M-theory. We also comment on singularities and the issue of chirality changing transitions in the exact background. The exact background is then applied to determine Newton's Constant for vacua with an M5 brane on the basis of a recent stabilization mechanism for the orbifold length. For vacua without M5 brane we obtain a correction to the lower bound on Newton's Constant which brings it in perfect agreement with the measured value.Comment: 30 pages, 2 figures, v2: references added, v3: more references added, v4: 11d exact solution shown to be origin of 5d domain wall solutio