Statistical mechanics and thermodynamics of viral evolution

This paper analyzes a simplified model of viral infection and evolution using the 'grand canonical ensemble' and formalisms from statistical mechanics and thermodynamics to enumerate all possible viruses and to derive thermodynamic variables for the system. We model the infection process as a series of energy barriers determined by the genetic states of the virus and host as a function of immune response and system temperature. We find a phase transition between a positive temperature regime of normal replication and a negative temperature 'disordered' phase of the virus. These phases define different regimes in which different genetic strategies are favored. Perhaps most importantly, it demonstrates that the system has a real thermodynamic temperature. For normal replication, this temperature is linearly related to effective temperature. The strength of immune response rescales temperature but does not change the observed linear relationship. For all temperatures and immunities studied, we find a universal curve relating the order parameter to viral evolvability. Real viruses have finite length RNA segments that encode for proteins which determine their fitness; hence the methods put forth here could be refined to apply to real biological systems, perhaps providing insight into immune escape, the emergence of novel pathogens and other results of viral evolution.Comment: 39 pages (55 pages including supplement), 9 figures, 11 supplemental figure

An extensible spatial and temporal epidemiological modelling system

BACKGROUND: This paper describes the Spatiotemporal Epidemiological Modeller (STEM) which is an extensible software system and framework for modelling the spatial and temporal progression of multiple diseases affecting multiple populations in geographically distributed locations. STEM is an experiment in developing a software system that can model complex epidemiological scenarios while also being extensible by the research community. The ultimate goal of STEM is to provide a common modelling platform powerful enough to be sufficient for all modelling scenarios and extensible in a way that allows different researchers to combine their efforts in developing exceptionally good models. RESULTS: STEM is a powerful modelling system that allows researchers to model scenarios with unmixed populations that are not uniformly distributed and in which multiple populations exist that are being infected with multiple diseases. It's underlying representational framework, a graph, and its software architecture allow the system to be extended by incorporating software components developed by different researchers. CONCLUSION: This approach taken in the design of STEM creates a powerful platform for epidemiological research collaboration. Future versions of the system will make such collaborative efforts easy and common

Measuring Creativity for Innovation Management

Identifying the extent and nature of the creativity of new products is a key for innovation management. The revised Creative Solution Diagnosis Scale (CSDS) is a 27-item scale based on a theoretical model of functional creativity, consisting of five main criteria: Relevance & Effectiveness, Problematization, Propulsion, Elegance and Genesis. The CSDS offers potential for differentiated assessments of product creativity as part of the larger process of innovation. Non-expert judges rated a series of mousetrap designs using a 30-item version of the CSDS. Confirmatory factor analysis revealed a simple structure that corresponded closely to the a priori theoretical model of functional creativity. The untrained judges were able to use the scale with a high degree of reliability and internal consistency. The scale offers a tool for managing innovation, especially for stimulating creativity and diagnosing the creativity of products

Structure of the southern Keweenawan rift from COCORP surveys across the Midcontinent Geophysical Anomaly in northeastern Kansas

This is the published version. Copyright 1984 American Geophysical Union. All Rights Reserved.COCORP profiling across the midcontinent geophysical anomaly in northeastern Kansas reveals structural basins and other features of the Precambrian Keweenawan rift buried beneath the Phanerozoic cover. The 40-km-wide main basin is asymmetric, with a maximum depth of 3 km on the east and 8 km on the west. The basin fill is characterized by a lower layered sequence of strong continuous west dipping reflectors which may be correlated with Middle Keweenawan interbedded volcanic and clastic rocks exposed along the MGA in the Lake Superior region. Overlying this layered sequence is a zone of weak, discontinuous reflectors correlated here with the predominantly clastic rocks characteristic of the Upper Keweenawan sequence near Lake Superior. A second tilted but shallower basin lies to the east of the main basin and appears to be filled predominantly with clastic sedimentary rocks. The character of the seismic data, the seismic velocity distribution, and gravity modeling suggest that mafic intrusions lie beneath the main rift basin. Normal faults associated with the rift dip at moderate angles to the east. Palinspastic reconstruction indicates that the rift basin formed by the rotation of fault bounded blocks during crustal extension. Although reactivation of preexisting structures appears to have occurred in many other rifts profiled by COCORP, the evidence is inconclusive on this point in the case of the Kansas data. The structures mapped by COCORP surveys in Kansas and elsewhere suggest that asymmetric sequences of layered reflectors are characteristic, and perhaps diagnostic, of rift basin deposits in general

Educating International Security Practitioners: Preparing to Face the Demands of the 21st Century International Security Environment

The authors examine the challenges of the 21st century international security environment to which future strategic leaders and policy practitioners will need to respond. More specifically, they offer the reader insights into security studies and leadership development at their respective levels (military undergraduate, civilian undergraduate, traditional and nontraditional graduate, and senior military officer) and institutions (including research centers and professional outreach programs). The goal is to inform a broader audience about what is currently being done in the way of educating strategic practitioners at these various institutions, and what might need to be done differently or better.https://press.armywarcollege.edu/monographs/1835/thumbnail.jp

Increased Severity of HSV-1 Keratitis and Mortality in Mice Lacking The 2–5A-Dependent RNase L Gene

Purpose: The2′,5′-oligoadenylate-dependent RNase L gene functions in the interferon-inducible RNA decay pathway known as the 2–5A system. The purpose of this study was to determine whether the absence of this gene affects the pathogenesis of herpes simplex virus type 1 (HSV-1) ocular infection in the mouse. Methods: HSV-1 (strain McKrae) was applied bilaterally to unscarified corneas of RNase L–null mice and congenic controls. To evaluate the severity of herpetic keratitis, slit lamp examinations (SLE) were performed every other day for 14 days. To study corneal histology and apoptosis, HSV-1–inoculated RNase-L-null and congenic control mice, as well as mock-inoculated mice (apoptosis negative control), were killed at 6 and 18 hours postinoculation (PI). Uninoculated mice that underwent corneal scarification (apoptosis positive control) were killed 2 hours after scarification. Eyes were dissected and the corneas processed for light and transmission electron microscopy and the TUNEL assay. Results: In comparison with the congenic control mice, RNase L–null mice showed significantly more severe herpetic keratitis (PI day 8, SLE score, mean ± SEM: 3.27 ± 0.10 vs. 2.34 ± 0.06; P \u3c 0.001) and significantly higher mortality (PI day 14, 70% vs. 20%; P \u3c 0.001). Few apoptotic cells were seen in HSV-1–infected RNase L–null mice, although DNA fragmentation consistent with apoptosis was detected in the corneas of congenic control mice 6 and 18 hours after HSV-1 inoculation and in uninfected mice with scarified corneas. Signs of apoptosis were not present in the mock-infected corneas. Electron microscopic evidence of keratocytic apoptosis was detected only in the uninfected scarified corneas and the HSV-1–infected congenic control corneas. Conclusions: The increased severity of ocular disease and increased mortality in the RNase L–null mice provides evidence, for the first time, that the 2–5A system contributes to protection during ocular herpetic infection. The reduced frequency of apoptosis in these mice suggests that one possible mechanism for this protective effect could be the induction of apoptosis in corneal cells as a means of reducing the spread of infectious virus

The business of genomic testing: a survey of early adopters

Purpose: The practice of “genomic” (or “personalized”) medicine requires the availability of appropriate diagnostic testing. Our study objective was to identify the reasons for health systems to bring next-generation sequencing into their clinical laboratories and to understand the process by which such decisions were made. Such information may be of value to other health systems seeking to provide next-generation sequencing testing to their patient populations. Methods: A standardized open-ended interview was conducted with the laboratory medical directors and/or department of pathology chairs of 13 different academic institutions in 10 different states. Results: Genomic testing for cancer dominated the institutional decision making, with three primary reasons: more effective delivery of cancer care, the perceived need for institutional leadership in the field of genomics, and the premise that genomics will eventually be cost-effective. Barriers to implementation included implementation cost; the time and effort needed to maintain this newer testing; challenges in interpreting genetic variants; establishing the bioinformatics infrastructure; and curating data from medical, ethical, and legal standpoints. Ultimate success depended on alignment with institutional strengths and priorities and working closely with institutional clinical programs. Conclusion: These early adopters uniformly viewed genomic analysis as an imperative for developing their expertise in the implementation and practice of genomic medicine