Allosteric modulation of DNA by small molecules

Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways. Pyrrole-imidazole polyamides are DNA minor-groove binding molecules that are programmable for a large repertoire of DNA motifs. A high resolution X-ray crystal structure of an 8-ring cyclic Py/Im polyamide bound to the central 6 bp of the sequence d(5′-CCAGGCCTGG-3′)2 reveals a 4 Å widening of the minor groove and compression of the major groove along with a >18 ° bend in the helix axis toward the major groove. This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor-DNA interfaces by small molecules, a minimum step in chemical control of gene networks

Proposed Category System for 1960-2000 Census Occupations

This paper proposes a detailed, consistent category system for occupations in the Census of Population data from 1960 to 2000. Most of the categories are based on the 1990 Census occupation definitions. We analyze employment levels, average earnings levels, and earnings variance in our occupation categories over time, compare these to similar trends for occupations defined in the occ1950 IPUMS classification, and test both classifications for consistency over time.occupations; jobs; classification; categories; metadata; Census; IPUMS

Activating the 4th Neutrino of the 3+1 Scheme

Non-Standard Interactions (NSI) of neutrinos with matter has received renewed interest in recent years. In particular, it has been shown that NSI can reconcile the $3+1$ solution with IceCube atmospheric data with $E_\nu >500$ GeV, provided that the effective coupling of NSI is large, e.g. $\sim 6 G_F$. The main goal of the present paper is to show that contrary to intuition, it is possible to build viable models with large NSI by invoking a new $U(1)$ gauge symmetry with gauge boson of mass $\sim 10$ eV. We refer to these new constructions as $3+1+ U(1)$ models. In the framework of a $3+1$ solution to LSND and MiniBooNE anomalies, we show that this novel NSI can help to solve the tension with cosmological bounds and constraints from IceCube atmospheric data with $E_\nu>500$ GeV. We then discuss the implications of the MINOS and MINOS+ results for the 3+1+$U(1)$ scenario.Comment: 24 pages, 5 figure

Testing the Role of Technical Information in Public Risk Perception

It is widely believed that more detail about health effects and likely exposure routes is apt to reduce citizens\u27 concerns about low-probability Risks. The authors\u27 study suggests that providing such detail may not be as useful as, e.g., addressing public concerns and keeping citizens current on officials\u27 actions

Inflation meets neutrinos

Constraints on inflationary models typically assume only the standard models of cosmology and particle physics. By extending the neutrino sector to include a new interaction with a light scalar mediator ($m_{\phi}\sim$MeV), it is possible to relax these constraints, in particular via opening up regions of the parameter space of the spectral index $n_s$. These new interactions can be probed at IceCube via interactions of astrophysical neutrinos with the Cosmic Neutrino Background for nearly all of the relevant parameter space.Comment: 9 pages, 4 figures, comments welcom