Phenotypic mixing and hiding may contribute to memory in viral quasispecies

Background. In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, was found to avoid extinction and remain in the population for long periods of time. This observation was called quasispecies memory. The origin of quasispecies memory is not fully understood. Results. We propose and analyze a simple model of complementation between the wild type virus and a mutant that has an impaired ability of cell entry. The mutant will go extinct unless it is recreated from the wild type through mutations. However, under phenotypic mixing-and-hiding as a mechanism of complementation, the time to extinction in the absence of mutations increases with increasing multiplicity of infection (m.o.i.). The mutant's frequency at equilibrium under selection-mutation balance also increases with increasing m.o.i. At high m.o.i., a large fraction of mutant genomes are encapsidated with wild-type protein, which enables them to infect cells as efficiently as the wild type virions, and thus increases their fitness to the wild-type level. Moreover, even at low m.o.i. the equilibrium frequency of the mutant is higher than predicted by the standard quasispecies model, because a fraction of mutant virions generated from wild-type parents will also be encapsidated by wild-type protein. Conclusions. Our model predicts that phenotypic hiding will strongly influence the population dynamics of viruses, particularly at high m.o.i., and will also have important effects on the mutation--selection balance at low m.o.i. The delay in mutant extinction and increase in mutant frequencies at equilibrium may, at least in part, explain memory in quasispecies populations.Comment: 10 pages pdf, as published by BM

Tradeoff between short-term and long-term adaptation in a changing environment

We investigate the competition dynamics of two microbial or viral strains that live in an environment that switches periodically between two states. One of the strains is adapted to the long-term environment, but pays a short-term cost, while the other is adapted to the short-term environment and pays a cost in the long term. We explore the tradeoff between these alternative strategies in extensive numerical simulations, and present a simple analytic model that can predict the outcome of these competitions as a function of the mutation rate and the time scale of the environmental changes. Our model is relevant for arboviruses, which alternate between different host species on a regular basis.Comment: 9 pages, 3 figures, PRE in pres

A copula model for dependent competing risks

Many popular estimators for duration models require independent competing risks or independent censoring. In contrast, copula based estimators are also consistent in presence of dependent competing risks. In this paper we suggest a computationally convenient extension of the Copula Graphic Estimator (Zheng and Klein, 1995) to a model with more than two dependent competing risks. We analyse the applicability of this estimator by means of simulations and real world unemployment duration data from Germany. We obtain evidence that our estimator yields nice results if the dependence structure is known and that it is a powerful tool for the assessment of the relevance of (in-)dependence assumptions in applied duration research.Archimedean copula, dependent censoring, unemployment duration

A copula model for dependent competing risks

"Many popular estimators for duration models require independent competing risks or independent censoring. In contrast, copula based estimators are also consistent in presence of dependent competing risks. In this paper we suggest a computationally convenient extension of the Copula Graphic Estimator (Zheng and Klein, 1995) to a model with more than two dependent competing risks. We analyse the applicability of this estimator by means of simulations and real world unemployment duration data from Germany. We obtain evidence that our estimator yields nice results if the dependence structure is known and that it is a powerful tool for the assessment of the relevance of (in-)dependence assumptions in applied duration research." (Author's abstract, IAB-Doku) ((en)) Additional Information Appendix for the FDZ-Methodenreport No. 02/2009Risikoabschätzung - Modell, Wirkungsforschung - Methode, Methodologie, Arbeitsmarktpolitik - Erfolgskontrolle, ältere Arbeitnehmer, Leistungsanspruch - Dauer, Arbeitslosigkeitsdauer, IAB-Beschäftigtenstichprobe

High-efficiency, high-power difference-frequency generation of 0.9–1.5 μm light in BBO

An efficient method for generation of high energy pulsed ir light between 0.9 and 1.5 μm is described. The technique uses difference frequency mixing of pulsed, visible dye and Nd:YAG laser light in a 10 mm long BBO crystal. Quantum efficiencies of up to 23% and ir pulse energies up to 4.5 mJ are demonstrated. The low shot-to-shot fluctuations of difference frequency generation in BBO make this technique an attractive alternative to the conventional optical parametric oscillator or Raman shifting methods that are currently used to access this spectral region

Prohibiting Medical Method Patents: A Criticism of the Status Quo

Methods of medical treatment are not patentable in Canada. This means that inventions involving the performance of surgery, administration of medicine, or extraction of fluids or tissue for diagnostic tests cannot directly be protected under the current patent regime. However, this prohibition is not an absolute ban. Many medical innovations are patentable, including surgical tools and devices, drugs and other chemical compounds, medical “uses”, diagnostic assays and methods of treat- ing “natural” conditions. The practical reality is that the distinction between what is and what is not patentable is poorly defined. This uncertainty presents a steep challenge for inventors and patent agents in preparing patent claims that appropriately encapsulate a particular medical invention without claiming prohibited subject matter. This confusion also hinders the public and would-be inventors wishing to navigate the patent landscape. Part I of this paper entitled “Legal Basis for the Prohibition” summarizes the statutory and jurisprudential basis for prohibiting medical method patents. Part II entitled “Patentability of Medical Methods in Practice” discusses how this prohibition has been applied by courts and the Commissioner of Patents. Inconsistencies in its application are highlighted and practical guidance is provided on how to protect aspects of medical inventions without triggering the prohibition. Part III entitled “Criticism of the Status Quo” argues that the rationale for prohibiting medical method patents is tenuous, based more on public policy than the Patent Act. Based on the irregular application of the prohibition revealed in Part II and the criticisms raised in Part III, legislative reform is recommended

Bounds analysis of competing risks : a nonparametric evaluation of the effect of unemployment benefits on migration in Germany

"In this paper we derive nonparametric bounds for the cumulative incidence curve within a competing risks model with partly identified interval data. As an advantage over earlier attempts our approach also gives valid results in case of dependent competing risks. We apply our framework to empirically evaluate the effect of unemployment benefits on observed migration of unemployed workers in Germany. Our findings weakly indicate that reducing the entitlement length for unemployment benefits increases migration among high-skilled individuals." (Author's abstract, IAB-Doku) ((en))Arbeitslosenunterstützung, Leistungsanspruch - Dauer, Binnenwanderung, regionale Mobilität, Wanderungsmotivation, Mobilitätsbereitschaft, Arbeitslose, Hochqualifizierte, IAB-Beschäftigtenstichprobe