Patterns of nucleotide substitution in angiosperm cpDNA trnL (UAA)-trnF (GAA) regions

Patterns of substitution in chloroplast encoded trnL_F regions were compared between species of Actaea (Ranunculales), Digitalis (Scrophulariales), Drosera (Caryophyllales), Panicoideae (Poales), the small chromosome species clade of Pelargonium (Geraniales), each representing a different order of flowering plants, and Huperzia (Lycopodiales). In total, the study included 265 taxa, each with > 900-bp sequences, totaling 0.24 Mb. Both pairwise and phylogeny-based comparisons were used to assess nucleotide substitution patterns. In all six groups, we found that transition/transversion ratios, as estimated by maximum likelihood on most-parsimonious trees, ranged between 0.8 and 1.0 for ingroups. These values occurred both at low sequence divergences, where substitutional saturation, i.e., multiple substitutions having occurred at the same (homologous) nucleotide position, was not expected, and at higher levels of divergence. This suggests that the angiosperm trnL-F regions evolve in a pattern different from that generally observed for nuclear and animal mtDNA (transitional/transversion ratio > or = 2). Transition/transversion ratios in the intron and the spacer region differed in all alignments compared, yet base compositions between the regions were highly similar in all six groups. A>-C transversions were significantly less frequent than the other four substitution types. This correlates with results from studies on fidelity mechanisms in DNA replication that predict A<->T and G<->C transversions to be least likely to occur. It therefore strengthens confidence in the link between mutation bias at the polymerase level and the actual fixation of substitutions as recorded on evolutionary trees, and concomitantly, in the neutrality of nucleotide substitutions as phylogenetic markers.

The impact of maternal cortisol concentrations on child arterial elasticity

Epidemiological studies suggest that glucocorticoid excess in the fetus may contribute to the pathophysiology of cardiovascular diseases in adulthood. However, the impact of maternal glucocorticoid on the cardiovascular system of the offspring has not been much explored in studies involving humans, especially in childhood. The objective of this study was to assess the influence of maternal cortisol concentrations on child arterial elasticity. One hundred and thirty pregnant women followed from 1997 to 2000, and respective children 5-7 years of age followed from 2004 to 2006 were included in the study. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of nine samples of saliva. Arterial elasticity was assessed by the large artery elasticity index (LAEI; the capacitive elasticity of large arteries) by recording radial artery pulse wave, utilizing the equipment HDI/PulseWave CR-2000 Cardiovascular Profiling System (R). The nutritional status of the children was determined by the body mass index (BMI). Insulin concentration was assessed by chemiluminescence, and insulin resistance by the homeostasis model assessment. Blood glucose, total cholesterol and fractions (LDL-c and HDL-c) and triglyceride concentrations were determined by automated enzymatic methods. The association between maternal cortisol and child arterial elasticity was assessed by multivariate linear regression analysis. There was a statistically significant association between maternal cortisol and LAEI (P=0.02), controlling for birth weight, age, BMI and HDL-c of the children. This study suggests that exposure to higher glucocorticoid concentrations in the prenatal period is associated to lower arterial elasticity in childhood, an earlier cardiovascular risk marker.

Probing the dependence of the properties of cellulose acetates and their films on the degree of biopolymer substitution: use of solvatochromic indicators and thermal analysis

Although cellulose acetates, CAs, are extensively employed there is scant information about the systematic dependence of their properties on their degree of substitution, DS; this is the subject of the present work. Nine CAs samples, DS from 0.83 to 3.0 were synthesized; their films were prepared. The following solvatochromic probes have been employed in order to determine the empirical polarity, E (T)(33); ""acidity, alpha""; ""basicity, beta"", and ""dipolarity/polarizability, pi*"" of the casted films: 2,6-dichloro-4-(2,4,6-triphenyl-pyridinium-1-yl) phenolate, WB; 4-nitroaniline; 4-nitroanisole; 4-nitro-N,N-dimethylaniline; 2,6-diphenyl-4-(2,4,6-triphenyl-pyridinium-1-yl)phenolate, RB. Additionally, two systems, ethanol plus ethyl acetate (EtOH-EtAc), and cellulose plus cellulose triacetate, CTA, were employed as models for CAs of different DS. Regarding the model systems, the following was observed: (i) For EtOH-EtAc, the dependence of all solvatochromic parameters on the ""equivalent-DS"" of the binary mixture was non-linear because of preferential solvation; (ii) The dependence of E (T)(33) on equivalent DS of the cellulose-CTA films is linear, but the slope is smaller than that of the corresponding plot for CAs. This is attributed to the more efficient hydrogen bonding in the model system, a conclusion corroborated by IR measurements. The dependence of solvatochromic parameters of CAs on their DS is described by the simple equations; a consequence of the substitution of the OH by the ester group. The thermal properties of bulk CAs samples were investigated by DSC and TGA; their dependence on DS is described by simple equations. The relevance of these data to the processing and applications of CAs is briefly discussed.

Studies on Electrophilic Substitution Reactions of 3-Phenyl-cycl[3.2.2]azine

Acetylation and formylation of 3-phenyl-cycl[3.2.2]azine derivatives, in the presence of Lewis acids, have been Investigated. It has been found that the orientation of substitution in 2-carbomethoxy- 3-phenyl-cycl[3.2.2]azine for these two reactions, under Identical conditions, is different.

Determinants of Advertising Effectiveness: The Development of an International Advertising Elasticity Database and a Meta-Analysis

Increasing demand for marketing accountability requires an efficient allocation of marketing expenditures. Managers who know the elasticity of their marketing instruments can allocate their budgets optimally. Meta-analyses offer a basis for deriving benchmark elasticities for advertising. Although they provide a variety of valuable insights, a major shortcoming of prior meta-analyses is that they report only generalized results as the disaggregated raw data are not made available. This problem is highly relevant because coding of empirical studies, at least to a certain extent, involves subjective judgment. For this reason, meta-studies would be more valuable if researchers and practitioners had access to disaggregated data allowing them to conduct further analyses of individual, e.g., product-level-specific, interests. We are the first to address this gap by providing (1) an advertising elasticity database (AED) and (2) empirical generalizations about advertising elasticities and their determinants. Our findings indicate that the average current-period advertising elasticity is 0.09, which is substantially smaller than the value 0f 0.12 that was recently reported by Sethuraman, Tellis, and Briesch (2011). Furthermore, our meta-analysis reveals a wide range of significant determinants of advertising elasticity. For example, we find that advertising elasticities are higher (i) for hedonic and experience goods than for other goods; (ii) for new than for established goods; (iii) when advertising is measured in gross rating points (GRP) instead of absolute terms; and (iv) when the lagged dependent or lagged advertising variable is omitted.

Resin composites: Modulus of elasticity and marginal quality

OBJECTIVE To investigate how the modulus of elasticity of resin composites influences marginal quality in restorations submitted to thermocyclic and mechanical loading. METHODS Charisma, Filtek Supreme XTE and Grandio were selected as they were found to possess different moduli of elasticity but quite similar polymerization contraction. MOD cavities (n=30) were prepared in extracted premolars, restored and then subjected to thermocyclic and mechanical loading. Marginal quality of the restorations before and after loading was analyzed on epoxy replicas under a scanning electron microscope. The percentage of gap-free margins and occurrence of paramarginal fractures were registered. Modulus of elasticity and polymerization contraction were analyzed with parametric and margins with nonparametric ANOVA and post hoc Tukey HSD or Wilcoxon rank-sum tests, respectively. The number of paramarginal fractures was analyzed with exact Fisher tests (α=0.05). RESULTS Grandio demonstrated significantly more gap-free enamel margins than Charisma and Filtek Supreme XTE, before and after loading (p<0.01), whereas there was no difference between Charisma and Filtek Supreme XTE (p>0.05). No significant effect of resin composite (p=0.81) on the quality of dentine margins was observed, before or after loading. Deterioration of all margins was evident after loading (p<0.0001). More paramarginal enamel fractures were observed after loading in teeth restored with Grandio when compared to Charisma (p=0.008). CONCLUSIONS The resin composite with the highest modulus of elasticity resulted in the highest number of gap-free enamel margins but with an increased incidence of paramarginal enamel fractures. CLINICAL SIGNIFICANCE The results from this study suggest that the marginal quality of restorations can be improved by the selection of a resin composite with modulus of elasticity close to that of dentine, although an increase in paramarginal enamel fractures can result as a consequence.

STUDIES ON THE PATTERNS OF NUCLEOTIDE AND AMINO ACID SUBSTITUTION (ELECTROPHORESIS, MUTATION RATE, SELECTION, BASE, COMPOSITION)

Theoretical and empirical studies were conducted on the pattern of nucleotide and amino acid substitution in evolution, taking into account the effects of mutation at the nucleotide level and purifying selection at the amino acid level. A theoretical model for predicting the evolutionary change in electrophoretic mobility of a protein was also developed by using information on the pattern of amino acid substitution. The specific problems studied and the main results obtained are as follows: (1) Estimation of the pattern of nucleotide substitution in DNA nuclear genomes. The pattern of point mutations and nucleotide substitutions among the four different nucleotides are inferred from the evolutionary changes of pseudogenes and functional genes, respectively. Both patterns are non-random, the rate of change varying considerably with nucleotide pair, and that in both cases transitions occur somewhat more frequently than transversions. In protein evolution, substitution occurs more often between amino acids with similar physico-chemical properties than between dissimilar amino acids. (2) Estimation of the pattern of nucleotide substitution in RNA genomes. The majority of mutations in retroviruses accumulate at the reverse transcription stage. Selection at the amino acid level is very weak, and almost non-existent between synonymous codons. The pattern of mutation is very different from that in DNA genomes. Nevertheless, the pattern of purifying selection at the amino acid level is similar to that in DNA genomes, although selection intensity is much weaker. (3) Evaluation of the determinants of molecular evolutionary rates in protein-coding genes. Based on rates of nucleotide substitution for mammalian genes, the rate of amino acid substitution of a protein is determined by its amino acid composition. The content of glycine is shown to correlate strongly and negatively with the rate of substitution. Empirical formulae, called indices of mutability, are developed in order to predict the rate of molecular evolution of a protein from data on its amino acid sequence. (4) Studies on the evolutionary patterns of electrophoretic mobility of proteins. A theoretical model was constructed that predicts the electric charge of a protein at any given pH and its isoelectric point from data on its primary and quaternary structures. Using this model, the evolutionary change in electrophoretic mobilities of different proteins and the expected amount of electrophoretically hidden genetic variation were studied. In the absence of selection for the pI value, proteins will on the average evolve toward a mildly basic pI. (Abstract shortened with permission of author.) ^

Quality grading of cork stoppers based on porosity, density and elasticity.

An objective control method for grading cork stoppers is presented using a cork stopper quality index based on porosity, density and elasticity, these being the properties which have the greatest influence on the closure capacity of the stopper. The elasticity of the cork stopper is measured through the relaxation ratio, which is defined by the relationship between the relaxation force exerted by the cork in the bottleneck and the compressive force exerted by a caliper to fit the stopper in the bottle. The relaxation ratio, defined in this way, represents the part of the compression force which is applied to the stopper on insertion and which is recovered in the form of the relaxation force to achieve closure. The calculation of the relaxation ratio involves the measurement of the relaxation force of the fitted stopper. This force has been measured rigorously and precisely using a device developed in the Cork Laboratory at the INIA-CIFOR and which is presented for the first time in this paper.

The effects of changes in recycling patterns on United Kingdom resource consumption

Recycling, substitution and product life extension are identified as significant factors contributing to an extension of the time to exhaustion of industrially Dnportant materials. A quantitative assessment of the significance of virtually all materials to the U.K. is made. Copper is identified as one of the most important materials deserving of further investigation into potential resource savings through increased recycling. The other factors listed above are accounted for in the modelling technique employed. United Kingdom copper flows are qualitatively and statistically described for the years 1949 - 1976. Less accurate statistics are developed for 1922 - 1948. Adaptive expectations type causal models of total, unalloyed, and alloyed copper demand are successfully constructed and are used to generate future scenarios. Evidence is demonstrated for a break in the historical link between U.K. copper demand and industrial production. Simple causal models of potential copper scrap supply are constructed and a comparison made with actual old scrap withdrawals. Accurate adaptive expectations type models of total scrap demand are developed, but no conclusion is reached about the price elasticity of scrap demand. Various scenarios of copper goods demand are forecast and their effect on copper scrap demand. The potential to recover up to an extra 100.000 tonnes/year of generally lower grade old scrap is identified. Policy options are examined and the following recommendations made: 1) A total investment of up to £67 million in secondary refining capacity by the year 2000 is needed. 2) The copper scrap content of copper bearing goods should be specified to aid recovery. 3) A U.K. copper scrap buffer stock scheme would be advantageous for the secondary copper industry. Finally the methodology used is summarised for potential application to other materials.

Modelling and estimating models of physician labour supply and productivity

Ma thèse s’intéresse aux politiques de santé conçues pour encourager l’offre de services de santé. L’accessibilité aux services de santé est un problème majeur qui mine le système de santé de la plupart des pays industrialisés. Au Québec, le temps médian d’attente entre une recommandation du médecin généraliste et un rendez-vous avec un médecin spécialiste était de 7,3 semaines en 2012, contre 2,9 semaines en 1993, et ceci malgré l’augmentation du nombre de médecins sur cette même période. Pour les décideurs politiques observant l’augmentation du temps d’attente pour des soins de santé, il est important de comprendre la structure de l’offre de travail des médecins et comment celle-ci affecte l’offre des services de santé. Dans ce contexte, je considère deux principales politiques. En premier lieu, j’estime comment les médecins réagissent aux incitatifs monétaires et j’utilise les paramètres estimés pour examiner comment les politiques de compensation peuvent être utilisées pour déterminer l’offre de services de santé de court terme. En second lieu, j’examine comment la productivité des médecins est affectée par leur expérience, à travers le mécanisme du "learning-by-doing", et j’utilise les paramètres estimés pour trouver le nombre de médecins inexpérimentés que l’on doit recruter pour remplacer un médecin expérimenté qui va à la retraite afin de garder l’offre des services de santé constant. Ma thèse développe et applique des méthodes économique et statistique afin de mesurer la réaction des médecins face aux incitatifs monétaires et estimer leur profil de productivité (en mesurant la variation de la productivité des médecins tout le long de leur carrière) en utilisant à la fois des données de panel sur les médecins québécois, provenant d’enquêtes et de l’administration. Les données contiennent des informations sur l’offre de travail de chaque médecin, les différents types de services offerts ainsi que leurs prix. Ces données couvrent une période pendant laquelle le gouvernement du Québec a changé les prix relatifs des services de santé. J’ai utilisé une approche basée sur la modélisation pour développer et estimer un modèle structurel d’offre de travail en permettant au médecin d’être multitâche. Dans mon modèle les médecins choisissent le nombre d’heures travaillées ainsi que l’allocation de ces heures à travers les différents services offerts, de plus les prix des services leurs sont imposés par le gouvernement. Le modèle génère une équation de revenu qui dépend des heures travaillées et d’un indice de prix représentant le rendement marginal des heures travaillées lorsque celles-ci sont allouées de façon optimale à travers les différents services. L’indice de prix dépend des prix des services offerts et des paramètres de la technologie de production des services qui déterminent comment les médecins réagissent aux changements des prix relatifs. J’ai appliqué le modèle aux données de panel sur la rémunération des médecins au Québec fusionnées à celles sur l’utilisation du temps de ces mêmes médecins. J’utilise le modèle pour examiner deux dimensions de l’offre des services de santé. En premierlieu, j’analyse l’utilisation des incitatifs monétaires pour amener les médecins à modifier leur production des différents services. Bien que les études antérieures ont souvent cherché à comparer le comportement des médecins à travers les différents systèmes de compensation,il y a relativement peu d’informations sur comment les médecins réagissent aux changementsdes prix des services de santé. Des débats actuels dans les milieux de politiques de santé au Canada se sont intéressés à l’importance des effets de revenu dans la détermination de la réponse des médecins face à l’augmentation des prix des services de santé. Mon travail contribue à alimenter ce débat en identifiant et en estimant les effets de substitution et de revenu résultant des changements des prix relatifs des services de santé. En second lieu, j’analyse comment l’expérience affecte la productivité des médecins. Cela a une importante implication sur le recrutement des médecins afin de satisfaire la demande croissante due à une population vieillissante, en particulier lorsque les médecins les plus expérimentés (les plus productifs) vont à la retraite. Dans le premier essai, j’ai estimé la fonction de revenu conditionnellement aux heures travaillées, en utilisant la méthode des variables instrumentales afin de contrôler pour une éventuelle endogeneité des heures travaillées. Comme instruments j’ai utilisé les variables indicatrices des âges des médecins, le taux marginal de taxation, le rendement sur le marché boursier, le carré et le cube de ce rendement. Je montre que cela donne la borne inférieure de l’élasticité-prix direct, permettant ainsi de tester si les médecins réagissent aux incitatifs monétaires. Les résultats montrent que les bornes inférieures des élasticités-prix de l’offre de services sont significativement positives, suggérant que les médecins répondent aux incitatifs. Un changement des prix relatifs conduit les médecins à allouer plus d’heures de travail au service dont le prix a augmenté. Dans le deuxième essai, j’estime le modèle en entier, de façon inconditionnelle aux heures travaillées, en analysant les variations des heures travaillées par les médecins, le volume des services offerts et le revenu des médecins. Pour ce faire, j’ai utilisé l’estimateur de la méthode des moments simulés. Les résultats montrent que les élasticités-prix direct de substitution sont élevées et significativement positives, représentant une tendance des médecins à accroitre le volume du service dont le prix a connu la plus forte augmentation. Les élasticitésprix croisées de substitution sont également élevées mais négatives. Par ailleurs, il existe un effet de revenu associé à l’augmentation des tarifs. J’ai utilisé les paramètres estimés du modèle structurel pour simuler une hausse générale de prix des services de 32%. Les résultats montrent que les médecins devraient réduire le nombre total d’heures travaillées (élasticité moyenne de -0,02) ainsi que les heures cliniques travaillées (élasticité moyenne de -0.07). Ils devraient aussi réduire le volume de services offerts (élasticité moyenne de -0.05). Troisièmement, j’ai exploité le lien naturel existant entre le revenu d’un médecin payé à l’acte et sa productivité afin d’établir le profil de productivité des médecins. Pour ce faire, j’ai modifié la spécification du modèle pour prendre en compte la relation entre la productivité d’un médecin et son expérience. J’estime l’équation de revenu en utilisant des données de panel asymétrique et en corrigeant le caractère non-aléatoire des observations manquantes à l’aide d’un modèle de sélection. Les résultats suggèrent que le profil de productivité est une fonction croissante et concave de l’expérience. Par ailleurs, ce profil est robuste à l’utilisation de l’expérience effective (la quantité de service produit) comme variable de contrôle et aussi à la suppression d’hypothèse paramétrique. De plus, si l’expérience du médecin augmente d’une année, il augmente la production de services de 1003 dollar CAN. J’ai utilisé les paramètres estimés du modèle pour calculer le ratio de remplacement : le nombre de médecins inexpérimentés qu’il faut pour remplacer un médecin expérimenté. Ce ratio de remplacement est de 1,2.

Carbon Stocks in Compartments of Soil Organic Matter 31 Years after Substitution of Native Cerrado Vegetation by Agroecosystems.

ABSTRACT: Changes in carbon stocks in different compartments of soil organic matter of a clayey Latossolo Vermelho Distrófico (Typic Haplustox), caused by the substitution of native savanna vegetation (cerrado sensu stricto) by agroecosystems, were assessed after 31 years of cultivation. Under native vegetation, a stock of 164.5 Mg ha-1 C was estimated in the 0.00-1.00 m layer. After 31 years of cultivation, these changes in soil C stocks were detected to a depth of 0.60 m. In the case of substitution of cerrado sensu stricto by no-tillage soybean-corn rotation, a reduction of at least 11 % of the soil C pools was observed. However, the adoption of no-tillage as an alternative to tillage with a moldboard plow (conventional system) reduced CO2 emissions by up to 12 %.

Distribution of benefits of irrigation induced technological changes and commodity markets : new evidence

A plethora of literature exists on irrigation development. However, only a few studies analyse the distributional issues associated with irrigation induced technological changes (IITC) in the context of commodity markets. Furthermore, these studies deal with only the theoretical arguments and to date no proper investigation has been conducted to examine the long-term benefits of adopting modern irrigation technology. This study investigates the long-term benefit changes of irrigation induced technological changes using data from Sri Lanka with reference to rice farming. The results show that (1) adopting modern technology on irrigation increases the overall social welfare through consumption of a larger quantity at a lower cost (2) the magnitude, sensitivity and distributional gains depend on the price elasticity of demand and supply as well as the size of the marketable surplus (3) non-farm sector gains are larger than farm sector gains (4) the distribution of the benefits among different types of producers depend on the magnitude of the expansion of the irrigated areas as well as the competition faced by traditional farmers (5) selective technological adoption and subsidies have a detrimental effect on the welfare of other producers who do not enjoy the same benefits (6) the short-term distributional effects are more severe than the long-term effects among different groups of farmers.

Analysis of linear relationships in block ciphers

This thesis is devoted to the study of linear relationships in symmetric block ciphers. A block cipher is designed so that the ciphertext is produced as a nonlinear function of the plaintext and secret master key. However, linear relationships within the cipher can still exist if the texts and components of the cipher are manipulated in a number of ways, as shown in this thesis. There are four main contributions of this thesis. The first contribution is the extension of the applicability of integral attacks from word-based to bitbased block ciphers. Integral attacks exploit the linear relationship between texts at intermediate stages of encryption. This relationship can be used to recover subkey bits in a key recovery attack. In principle, integral attacks can be applied to bit-based block ciphers. However, specific tools to define the attack on these ciphers are not available. This problem is addressed in this thesis by introducing a refined set of notations to describe the attack. The bit patternbased integral attack is successfully demonstrated on reduced-round variants of the block ciphers Noekeon, Present and Serpent. The second contribution is the discovery of a very small system of equations that describe the LEX-AES stream cipher. LEX-AES is based heavily on the 128-bit-key (16-byte) Advanced Encryption Standard (AES) block cipher. In one instance, the system contains 21 equations and 17 unknown bytes. This is very close to the upper limit for an exhaustive key search, which is 16 bytes. One only needs to acquire 36 bytes of keystream to generate the equations. Therefore, the security of this cipher depends on the difficulty of solving this small system of equations. The third contribution is the proposal of an alternative method to measure diffusion in the linear transformation of Substitution-Permutation-Network (SPN) block ciphers. Currently, the branch number is widely used for this purpose. It is useful for estimating the possible success of differential and linear attacks on a particular SPN cipher. However, the measure does not give information on the number of input bits that are left unchanged by the transformation when producing the output bits. The new measure introduced in this thesis is intended to complement the current branch number technique. The measure is based on fixed points and simple linear relationships between the input and output words of the linear transformation. The measure represents the average fraction of input words to a linear diffusion transformation that are not effectively changed by the transformation. This measure is applied to the block ciphers AES, ARIA, Serpent and Present. It is shown that except for Serpent, the linear transformations used in the block ciphers examined do not behave as expected for a random linear transformation. The fourth contribution is the identification of linear paths in the nonlinear round function of the SMS4 block cipher. The SMS4 block cipher is used as a standard in the Chinese Wireless LAN Wired Authentication and Privacy Infrastructure (WAPI) and hence, the round function should exhibit a high level of nonlinearity. However, the findings in this thesis on the existence of linear relationships show that this is not the case. It is shown that in some exceptional cases, the first four rounds of SMS4 are effectively linear. In these cases, the effective number of rounds for SMS4 is reduced by four, from 32 to 28. The findings raise questions about the security provided by SMS4, and might provide clues on the existence of a flaw in the design of the cipher.

Evaluation cortical bone elasticity in response to pulse power excitation using ultrasonic technique

This paper presents the ultrasonic velocity measurement method which investigates the possible effects of high voltage high frequency pulsed power on cortical bone material elasticity. Before applying a pulsed power signal on a live bone, it is essential to determine the safe parameters of pulsed power applied on bone non-destructively. Therefore, the possible changes in cortical bone material elasticity due to a specified pulsed power excitation have been investigated. A controllable positive buck-boost converter with adjustable output voltage and frequency has been used to generate high voltage pulses (500V magnitude at 10 KHz frequency). To determine bone elasticity, an ultrasonic velocity measurement has been conducted on two groups of control (unexposed to pulse power but in the same environmental condition) and cortical bone samples exposed to pulsed power. Young’s modulus of cortical bone samples have been determined and compared before and after applying the pulsed power signal. After applying the high voltage pulses, no significant variation in elastic property of cortical bone specimens was found compared to the control. The result shows that pulsed power with nominated parameters can be applied on cortical bone tissue without any considerable negative effect on elasticity of bone material.

Accounting for calibration uncertainty in phylogenetic estimation of evolutionary divergence times

The estimation of phylogenetic divergence times from sequence data is an important component of many molecular evolutionary studies. There is now a general appreciation that the procedure of divergence dating is considerably more complex than that initially described in the 1960s by Zuckerkandl and Pauling (1962, 1965). In particular, there has been much critical attention toward the assumption of a global molecular clock, resulting in the development of increasingly sophisticated techniques for inferring divergence times from sequence data. In response to the documentation of widespread departures from clocklike behavior, a variety of local- and relaxed-clock methods have been proposed and implemented. Local-clock methods permit different molecular clocks in different parts of the phylogenetic tree, thereby retaining the advantages of the classical molecular clock while casting off the restrictive assumption of a single, global rate of substitution (Rambaut and Bromham 1998; Yoder and Yang 2000).