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61.
We consider the directed evolution of a population after an intervention that has significantly altered the underlying fitness landscape. We model the space of genotypes as a distributive lattice; the fitness landscape is a real-valued function on that lattice. The risk of escape from intervention, i.e., the probability that the population develops an escape mutant before extinction, is encoded in the risk polynomial. Tools from algebraic combinatorics are applied to compute the risk polynomial in terms of the fitness landscape. In an application to the development of drug resistance in HIV, we study the risk of viral escape from treatment with the protease inhibitors ritonavir and indinavir.  相似文献   
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Increasing body of experimental evidence suggests that anticancer and antimicrobial therapies may themselves promote the acquisition of drug resistance by increasing mutability. The successful control of evolving populations requires that such biological costs of control are identified, quantified and included to the evolutionarily informed treatment protocol. Here we identify, characterise and exploit a trade-off between decreasing the target population size and generating a surplus of treatment-induced rescue mutations. We show that the probability of cure is maximized at an intermediate dosage, below the drug concentration yielding maximal population decay, suggesting that treatment outcomes may in some cases be substantially improved by less aggressive treatment strategies. We also provide a general analytical relationship that implicitly links growth rate, pharmacodynamics and dose-dependent mutation rate to an optimal control law. Our results highlight the important, but often neglected, role of fundamental eco-evolutionary costs of control. These costs can often lead to situations, where decreasing the cumulative drug dosage may be preferable even when the objective of the treatment is elimination, and not containment. Taken together, our results thus add to the ongoing criticism of the standard practice of administering aggressive, high-dose therapies and motivate further experimental and clinical investigation of the mutagenicity and other hidden collateral costs of therapies.  相似文献   
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Human toxocariasis (HT) is a zoonotic disease caused by infection with the larval stage of Toxocara canis, the intestinal roundworm of dogs. Infection can be associated with a wide clinical spectrum varying from asymptomatic to severe organ injury. While the incidence of symptomatic human toxocariasis appears to be low, infection of the human population is widespread. In Cuba, a clear overview on the status of the disease is lacking. Here, we review the available information on toxocariasis in Cuba as a first step to estimate the importance of the disease in the country. Findings are discussed and put in a broader perspective. Data gaps are identified and suggestions on how to address these are presented. The available country data suggest that Toxocara infection of the definitive dog host and environmental contamination with Toxocara spp. eggs is substantial, but information on HT is less conclusive. The availability of adequate diagnostic tools in the country should be guaranteed. Dedicated studies are needed for a reliable assessment of the impact of toxocariasis in Cuba and the design of prevention or control strategies.  相似文献   
66.
Identification of persons through the eyes is in the field of biometrical science. Many security systems are based on biometric methods of personal identification, to determine whether a person is presenting itself truly. The human eye contains an extremely large number of individual characteristics that make it particularly suitable for the process of identifying a person. Today, the eye is considered to be one of the most reliable body parts for human identification. Systems using iris recognition are among the most secure biometric systems.  相似文献   
67.
Some carnation species (Dianthus spp., Caryophyllaceae) exhibit a strong resistance to drought stress that is connected with the increased surface wax formation. Wax composition is unknown for the majority of Dianthus spp. Herein, mass spectral and gas chromatographic data, in combination with synthesis and chemical transformations (transesterification and synthesis of dimethyl disulfide adducts), enabled the identification of 151 constituents of diethyl‐ether washings of fresh flowers of Dianthus cruentus Griseb . from Serbia. The flower wax contained, along with the dominant ubiquitous long‐chain n‐alkanes, homologous series of n‐ and branched (iso‐ and anteiso‐) long‐chain hexyl alkanoates/alkenoates and alkyl/alkenyl benzoates. The branching position in the mentioned hexyl esters was probed by synthesis of esters of three isomeric hexanols that were spectrally characterized (1H‐ and 13C‐NMR, IR, MS). The washings also contained long‐chain (Z)‐ and (E)‐alkenes (C23?C35) with several different double bond regiochemistries. Fifty‐five of these constituents (eight hexyl esters, two benzoates, and forty‐five alkenes) were detected for the first time in Plantae, while ten of these represent completely new compounds. The rare occurrence of these wax constituents makes them possible chemotaxonomic markers of this particular Dianthus sp.  相似文献   
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Research on evolutionary forces determining optimal body sizes has primarily relied on experimental evaluation of respective selective pressures. Accounting for among‐species variation through application of phylogenetic comparative methods is a complementary although little used approach. It enables the direct association of body size values with particular environments. Using phylogenetically explicit comparative analyses, we show that small body size is associated with diurnal (rather than nocturnal) activity of adults among temperate species of the moth family Geometridae. The association of an exclusively adult trait with species‐specific body size suggests that optimal body sizes are at least partly determined by the costs being a large adult, as opposed to the more frequently considered costs of attaining large size. It appears likely that size‐selective predation by insectivorous birds is the primary factor responsible for selection against large body size in day‐flying moths.  相似文献   
69.
The long-term stability and success of orthopedic implants depend on the osseointegration process, which is strongly influenced by the biomaterial surface. A promising approach to enhance implant integration involves the modification of the surface of the implant by means of polymers that mimic the natural components of the extracellular matrix, for example, polysaccharides. In this study, methacrylate thermosets (bisphenol A glycidylmethacrylate/triethyleneglycol dimethacrylate), a widely used composition for orthopedic and dental applications, have been coated by electrostatic deposition of a bioactive chitosan-derivative. This polysaccharide was shown to induce osteoblasts aggregation in vitro, to stimulate cell proliferation and to enhance alkaline phosphatase activity. The coating deposition was studied by analyzing the effect of pH and ionic strength on the grafting of the polysaccharide. Contact angle studies show that the functionalized material displays a higher hydrophilic character owing to the increase of surface polar groups. The mechanical properties of the coating were evaluated by nanoindentation studies which point to higher values of indentation hardness and modulus (E) of the polysaccharide surface layer, while the influence of cyclic stress on the construct was assessed by fatigue tests. Finally, in vivo tests in minipigs showed that the polysaccharide-based implant showed a good biocompatibility and an ability for osseointegration at least similar to that of the titanium Ti6Al4V alloy with roughened surface.  相似文献   
70.
The effect of variations in H2 concentrations on methanogenesis from the non-competitive substrates methanol and methylamine (used by methanogens but not by sulfate reducers) was investigated in methanogenic marine sediments. Imposed variations in sulfate concentration and temperature were used to drive systematic variations in pore water H2 concentrations. Specifically, increasing sulfate concentrations and decreasing temperatures both resulted in decreasing H2 concentrations. The ratio of CO2 and CH4 produced from 14C-labelled methylamine and methanol showed a direct correlation with the H2 concentration, independent of the treatment, with lower H2 concentrations resulting in a shift towards CO2. We conclude that this correlation is driven by production of H2 by methylotrophic methanogens, followed by loss to the environment with a magnitude dependent on the extracellular H2 concentrations maintained by hydrogenotrophic methanogens (in the case of the temperature experiment) or sulfate reducers (in the case of the sulfate experiment). Under sulfate-free conditions, the loss of reducing power as H2 flux out of the cell represents a loss of energy for the methylotrophic methanogens while, in the presence of sulfate, it results in a favourable free energy yield. Thus, hydrogen leakage might conceivably be beneficial for methanogens in marine sediments dominated by sulfate reduction. In low-sulfate systems such as methanogenic marine or freshwater sediments it is clearly detrimental--an adverse consequence of possessing a hydrogenase that is subject to externally imposed control by pore water H2 concentrations. H2 leakage in methanogens may explain the apparent exclusion of acetoclastic methanogenesis in sediments dominated by sulfate reduction.  相似文献   
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