Sensitivity analysis for joint inversion of ground-penetratingradar and thermal-hydrological data from a large-scale underground heatertest

We describe a joint inversion approach that combinesgeophysical and thermal-hydrological data for the estimation of (1)thermal-hydrological parameters (such as permeability, porosity, thermalconductivity, and parameters of the capillary pressure and relativepermeability functions) that are necessary for predicting the flow offluids and heat in fractured porous media, and (2) parameters of thepetrophysical function that relates water saturation, porosity andtemperature to the dielectric constant. The approach incorporates thecoupled simulation of nonisothermal multiphase fluid flow andground-penetrating radar (GPR) travel times within an optimizationframework. We discuss application of the approach to a large-scale insitu heater test which was conducted at Yucca Mountain, Nevada, to betterunderstand the coupled thermal, hydrological, mechanical, and chemicalprocesses that may occur in the fractured rock mass around a geologicrepository for high-level radioactive waste. We provide a description ofthe time-lapse geophysical data (i.e., cross-borehole ground-penetratingradar) and thermal-hydrological data (i.e., temperature and water contentdata) collected before and during the four-year heating phase of thetest, and analyze the sensitivity of the most relevantthermal-hydrological and petrophysical parameters to the available data.To demonstrate feasibility of the approach, and as a first step towardcomprehensive inversion of the heater test data, we apply the approach toestimate one parameter, the permeability of the rock matrix

The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication

The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection

Homogeneous M2 duals

Motivated by the search for new gravity duals to M2 branes with $N>4$ supersymmetry --- equivalently, M-theory backgrounds with Killing superalgebra $\mathfrak{osp}(N|4)$ for $N>4$ --- we classify homogeneous M-theory backgrounds with symmetry Lie algebra $\mathfrak{so}(n) \oplus \mathfrak{so}(3,2)$ for $n=5,6,7$. We find that there are no new backgrounds with $n=6,7$ but we do find a number of new (to us) backgrounds with $n=5$. All backgrounds are metrically products of the form $\operatorname{AdS}_4 \times P^7$, with $P$ riemannian and homogeneous under the action of $\operatorname{SO}(5)$, or $S^4 \times Q^7$ with $Q$ lorentzian and homogeneous under the action of $\operatorname{SO}(3,2)$. At least one of the new backgrounds is supersymmetric (albeit with only $N=2$) and we show that it can be constructed from a supersymmetric Freund--Rubin background via a Wick rotation. Two of the new backgrounds have only been approximated numerically. (The second version of this paper includes an appendix by Alexander~S.~Haupt, closing a gap in our original analysis.)Comment: 56 page