Impact of sequence variation in the ul128 locus on production of human cytomegalovirus in fibroblast and epithelial cells

The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Quantitative temporal viromics: an approach to investigate host-pathogen interaction

A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection could provide dynamic insights into virus-host interaction. We developed a proteomic technique called “quantitative temporal viromics” (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but a paradigm of viral immune evasion. QTV detailed how HCMV orchestrates the expression of >8,000 cellular proteins, including 1,200 cell-surface proteins to manipulate signaling pathways and counterintrinsic, innate, and adaptive immune defenses. QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets. Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined. QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model

NIF Integrated Computer Controls System Description

This System Description introduces the NIF Integrated Computer Control System (ICCS). The architecture is sufficiently abstract to allow the construction of many similar applications from a common framework. As discussed below, over twenty software applications derived from the framework comprise the NIF control system. This document lays the essential foundation for understanding the ICCS architecture. The NIF design effort is motivated by the magnitude of the task. Figure 1 shows a cut-away rendition of the coliseum-sized facility. The NIF requires integration of about 40,000 atypical control points, must be highly automated and robust, and will operate continuously around the clock. The control system coordinates several experimental cycles concurrently, each at different stages of completion. Furthermore, facilities such as the NIF represent major capital investments that will be operated, maintained, and upgraded for decades. The computers, control subsystems, and functionality must be relatively easy to extend or replace periodically with newer technology

National Ignition Facility sub-system design requirements automatic alignment system SSDR 1.5.5

This System Design Requirement document establishes the performance, design, development, and test requirements for the Automatic Alignment System, which is part of the NIF Integrated Computer Control System (ICCS)

National Ignition Facility subsystem design requirements supervisory control software SSDR 1.5.2

This System Design Requirement document establishes the performance, design, development, and test requirements for the Supervisory Control Software, WBS 1.5.2, which is part of the NIF Integrated Computer Control System (ICCS). This document responds directly to the requirements detailed in ICCS (WBS 1-5)

National Ignition Facility sub-system design requirements computer system SSDR 1.5.1

This System Design Requirement document establishes the performance, design, development and test requirements for the Computer System, WBS 1.5.1 which is part of the NIF Integrated Computer Control System (ICCS). This document responds directly to the requirements detailed in ICCS (WBS 1.5) which is the document directly above