Modeling the survival of T-cell lymphocytes using compound branching processes

Radiotherapy has been a method of choice in cancer treatment for a number of years. Mathematical modeling is an important tool in studying the survival behavior of any cell as well as its radiosensitivity. One particular cell under investigation is the normal T-cell, the radiosensitivity of which may be indicative to the patient's tolerance to radiation doses.^ The model derived is a compound branching process with a random initial population of T-cells that is assumed to have compound distribution. T-cells in any generation are assumed to double or die at random lengths of time. This population is assumed to undergo a random number of generations within a period of time. The model is then used to obtain an estimate for the survival probability of T-cells for the data under investigation. This estimate is derived iteratively by applying the likelihood principle. Further assessment of the validity of the model is performed by simulating a number of subjects under this model.^ This study shows that there is a great deal of variation in T-cells survival from one individual to another. These variations can be observed under normal conditions as well as under radiotherapy. The findings are in agreement with a recent study and show that genetic diversity plays a role in determining the survival of T-cells. ^

Composition of minerals and rocks from the Markov Deep, Central Atlantic

The paper presents materials on composition and texture of weakly serpentinized ultrabasic rocks from the western and eastern walls of the Markov Deep (5°30.6'-5°32.4'N) in the rift valley of the Mid-Atlantic Ridge. Predominant harzburgites with protogranular and porphyroclastic textures contain two major generations of minerals: the first generation composes the bulk of rocks and consists of Ol_89.8-90.4 + En_90.2-90.8 + Di_91.8 + Chr (Cr#32.3-36.6, Mg#67.2-70.0), while the second generation composes very thin branching veinlets and consists of PlAn_32-47 + Ol_74.3-77.1 + Opx_55.7-71.9 + Cpx_67.5 + Amph_53.7-74.2 + Ilm. Syndeformational olivine neoblasts in recrystallization zones are highly magnesian. Concentrations and covariations of major elements in harzburgites indicate that these rocks are depleted in mantle residues (high Mg# of minerals and whole-rock samples and low in CaO, Al2O3, and TiO2) that are significantly enriched in trace HFSE and REE (Zr, Hf, Y, LREE, and all REE). Mineralogy and geochemistry of harzburgites were formed by interaction of mantle residues with hydrous, strongly fractionated melts that impregnated them. Mineral composition of veinlets in harzburgites and mineralogical-geochemical characteristics of related plagiogranites and gabbronorites suggest that these plagiogranites were produced by melt residuals after crystallization of gabbronorites. Modern characteristics of harzburgites were shaped by the following processes: (i) partial melting of mantle material simultaneously with its subsolidus deformations, (ii) brittle-plastic deformations associated with cataclastic flow and recrystallization, and (iii) melt percolation along zones of maximal stress relief and interaction of this melt with magnesian mantle residue.

The observatory of intelligence and territorial development, tool for innovation in processes of territorial planning in municipalities of the province of Jujuy

El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área

The observatory of intelligence and territorial development, tool for innovation in processes of territorial planning in municipalities of the province of Jujuy

El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área

The observatory of intelligence and territorial development, tool for innovation in processes of territorial planning in municipalities of the province of Jujuy

El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área

Sulfur and carbon in mIcrobial processes in waters and sediments of the Kara Sea in September 2007

Results of microbiological, biogeochemical and isotope geochemical studies in the Kara Sea are described. Samples for these studies were obtained during Cruise 54 of R/V Akademik Mstislav Keldysh in September 2007. The studied area covered the northern, central, and southwestern parts of the Kara Sea and the Obskaya Guba (Ob River estuary). Quantitative characteristics of total bacterial population and activity of microbial processes in the water column and bottom sediments were obtained. Total abundance of bacterioplankton (BP) varied from 250000 cells/ml in the northern Kara Sea to 3000000 cells/ml in the Obskaya Guba. BP abundance depended on concentration of suspensded matter. Net BP production was minimal in the central Kara Sea (up to 0.15-0.2 µg C/l/day) and maximal (0.5-0.75 µg C/l/day) in the Obskaya Guba. Organic material at the majority of stations at the Ob transect predominantly contained light carbon isotopes (-28.0 to -30.18 per mil) of terrigenous origin. Methane concentration in the surface water layer varied from 0.18 to 2.0 µl CH4/l, and methane oxidation rate varied from 0.1 to 100 nl CH4/l/day. Methane concentration in the upper sediment layer varied from 30 to 300 µl CH4/dm**3; rate of methane formation was varied from 44 to 500 nl CH4/dm**3/day and rate of methane oxidation - from 30 to 2000 nl CH4/dm**3/day. Rate of sulfate reduction varied from 4 to 184 µg S/dm**3/day.

Sm-Nd, Rb-Sr, and He isotopic composition and hydrocarbon gases in rocks and minerals from the Markov Deep, Mid-Atlantic Ridge rift valley

The paper presents characteristics of the Nd and Sr isotopic systems of ultrabasic rocks, gabbroids, plagiogranites, and their minerals as well as data on helium and hydrocarbons in fluid inclusions of the same samples. Materials presented in this publication were obtained by studying samples dredged from the MAR crest zone at 5°-6°N (U/Pb zircon dating, geochemical and petrological-mineralogical studies). It was demonstrated that variations in the isotopic composition of He entrapped in rocks and minerals were controlled by variable degrees of mixing of juvenile He, which is typical of basaltic glass for MAR (DM source), and atmospheric He. Increase in the atmospheric He fraction in plutonic rocks and, to a lesser degree, in their minerals reflects involvement of seawater or hydrated material of the oceanic crust in magmatic and postmagmatic processes. This conclusion finds further support in positive correlation between the fraction of mantle He (R ratio) and 87Sr/86Sr ratio. High-temperature hydration of ultrabasic rocks (amphibolization) was associated with increase in the fraction of mantle He, while their low-temperature hydration (serpentinization) was accompanied by drastic decrease in this fraction and significant increase in 87Sr/86Sr ratio. Insignificant variations in 143Nd/144Nd (close to 0.5130) and 87Sr/86Sr (0.7035) in most of gabbroids and plagiogranites as well as the fraction of mantle He in these rocks, amphibolites, and their ore minerals indicate that the melts were derived from the depleted mantle. Similar e-Nd values of gabbroids, plagiogranites, and fresh harzburgites (6.77-8.39) suggest that these rocks were genetically related to a single mantle source. e-Nd value of serpentinized lherzolites (2.62) likely reflects relations of these relatively weakly depleted mantle residues to another source. Aforementioned characteristics of the rocks generally reflect various degrees of mixing of depleted mantle components with crustal components (seawater) during metamorphic and hydrothermal processes that accompanied formation of the oceanic crust.

Seawater carbonate chemistry and biological processes of Limacina helicina during experiments, 2011

Due to their aragonitic shell, thecosome pteropods may be particularly vulnerable to ocean acidification driven by anthropogenic CO2 emissions. This applies specifically to species inhabiting Arctic surface waters that are projected to become temporarily and locally undersaturated with respect to aragonite as early as 2016. This study investigated the effects of rising partial pressure of CO2 (pCO2) and elevated temperature on pre-winter juveniles of the polar pteropod Limacina helicina. After a 29 day experiment in September/October 2009 at three different temperatures and under pCO2 scenarios projected for this century, mortality, shell degradation, shell diameter and shell increment were investigated. Temperature and pCO2 had a significant effect on mortality, but temperature was the overriding factor. Shell diameter, shell increment and shell degradation were significantly impacted by pCO2 but not by temperature. Mortality was 46% higher at 8 °C than at in situ temperature (3 °C), and 14% higher at 1100 ?atm than at 230 ?atm. Shell diameter and increment were reduced by 10 and 12% at 1100 ?atm and 230 ?atm, respectively, and shell degradation was 41% higher at elevated compared to ambient pCO2. We conclude that pre-winter juveniles will be negatively affected by both rising temperature and pCO2 which may result in a possible decline in abundance of the overwintering population, the basis for next year's reproduction.

Individual and population-level responses to ocean acidification

Ocean acidification is predicted to have detrimental effects on many marine organisms and ecological processes. Despite growing evidence for direct impacts on specific species, few studies have simultaneously considered the effects of ocean acidification on individuals (e.g. consequences for energy budgets and resource partitioning) and population level demographic processes. Here we show that ocean acidification increases energetic demands on gastropods resulting in altered energy allocation, i.e. reduced shell size but increased body mass. When scaled up to the population level, long-term exposure to ocean acidification altered population demography, with evidence of a reduction in the proportion of females in the population and genetic signatures of increased variance in reproductive success among individuals. Such increased variance enhances levels of short-term genetic drift which is predicted to inhibit adaptation. Our study indicates that even against a background of high gene flow, ocean acidification is driving individual- and population-level changes that will impact eco-evolutionary trajectories.

An Architecture forRepresenting Biological Processes based on Networks of Bio-inspired Processors

n this paper we propose the use of Networks of Bio-inspired Processors (NBP) to model some biological phenomena within a computational framework. In particular, we propose the use of an extension of NBP named Network Evolutionary Processors Transducers to simulate chemical transformations of substances. Within a biological process, chemical transformations of substances are basic operations in the change of the state of the cell. Previously, it has been proved that NBP are computationally complete, that is, they are able to solve NP complete problems in linear time, using massively parallel computations. In addition, we propose a multilayer architecture that will allow us to design models of biological processes related to cellular communication as well as their implications in the metabolic pathways. Subsequently, these models can be applied not only to biological-cellular instances but, possibly, also to configure instances of interactive processes in many other fields like population interactions, ecological trophic networks, in dustrial ecosystems, etc.

Del plan a la realidad: gobernanza y toma de decisiones en los procesos de regeneración urbana. El caso de Boston = From plan to reality: governance and decision-making in urban regeneration processes in Boston

En las últimas tres décadas, las dinámicas de restructuración económica a nivel global han redefinido radicalmente el papel de las ciudades. La transición del keynesianismo al neoliberalismo ha provocado un cambio en las políticas urbanas de los gobiernos municipales, que han abandonado progresivamente las tareas de regulación y redistribución para centrarse en la promoción del crecimiento económico y la competitividad. En este contexto, muchas voces críticas han señalado que la regeneración urbana se ha convertido en un vehículo de extracción de valor de la ciudad y está provocando la expulsión de los ciudadanos más vulnerables. Sin embargo, la regeneración de áreas consolidadas supone también una oportunidad de mejora de las condiciones de vida de la población residente, y es una política necesaria para controlar la expansión de la ciudad y reducir las necesidades de desplazamiento, promoviendo así ciudades más sostenibles. Partiendo de la hipótesis de que la gobernanza de los procesos de regeneración urbana es clave en el resultado final de las operaciones y determina el modelo de ciudad resultante, el objetivo de esta investigación es verificar si la regeneración urbana es necesariamente un mecanismo de extracción de valor o si puede mejorar la calidad de vida en las ciudades a través de la participación de los ciudadanos. Para ello, propone un marco de análisis del proceso de toma de decisiones en los planes de regeneración urbana y su impacto en los resultados de los planes, tomando como caso de estudio la ciudad de Boston, que desde los años 1990 trata de convertirse en una “ciudad de los barrios”, fomentando la participación ciudadana al tiempo que se posiciona en la escena económica global. El análisis se centra en dos operaciones de regeneración iniciadas a finales de los años 1990. Por un lado, el caso de Jackson Square nos permite comprender el papel de la sociedad civil y el tercer sector en la regeneración de los barrios más desfavorecidos, en un claro ejemplo de urbanismo “desde abajo” (bottom-up planning). Por otro, la reconversión del frente marítimo de South Boston para la construcción del Distrito de Innovación nos acerca a las grandes operaciones de regeneración urbana con fines de estímulo económico, tradicionalmente vinculadas a los centros financieros (downtown) y dirigidas por las élites gubernamentales y económicas (la growth machine) a través de procesos más tecnocráticos (top-down planning). La metodología utilizada consiste en el análisis cualitativo de los procesos de toma de decisiones y la relación entre los agentes implicados, así como de la evaluación de la implementación de dichas decisiones y su influencia en el modelo urbano resultante. El análisis de los casos permite afirmar que la gobernanza de los procesos de regeneración urbana influye decisivamente en el resultado final de las intervenciones; sin embargo, la participación de la comunidad local en la toma de decisiones no es suficiente para que el resultado de la regeneración urbana contrarreste los efectos de la neoliberalización, especialmente si se limita a la fase de planeamiento y no se extiende a la fase de ejecución, y si no está apoyada por una movilización política de mayor alcance que asegure una acción pública redistributiva. Asimismo, puede afirmarse que los procesos de regeneración urbana suponen una redefinición del modelo de ciudad, dado que la elección de los espacios de intervención tiene consecuencias sobre el equilibrio territorial de la ciudad. Los resultados de esta investigación tienen implicaciones para la disciplina del planeamiento urbano. Por una parte, se confirma la vigencia del paradigma del “urbanismo negociado”, si bien bajo discursos de liderazgo público y sin apelación al protagonismo del sector privado. Por otra parte, la planificación colaborativa en un contexto de “responsabilización” de las organizaciones comunitarias puede desactivar la potencia política de la participación ciudadana y servir como “amortiguador” hacia el gobierno local. Asimismo, la sustitución del planeamiento general como instrumento de definición de la ciudad futura por una planificación oportunista basada en la actuación en áreas estratégicas que tiren del resto de la ciudad, no permite definir un modelo coherente y consensuado de la ciudad que se desea colectivamente, ni permite utilizar el planeamiento como mecanismo de redistribución. ABSTRACT In the past three decades, the dynamics of global economic restructuring have radically redefined the role of cities. The transition from keynesianism to neoliberalism has caused a shift in local governments’ urban policies, which have progressively abandoned the tasks of regulation and redistribution to focus on promoting economic growth and competitiveness. In this context, many critics have pointed out that urban regeneration has become a vehicle for extracting value from the city and is causing the expulsion of the most vulnerable citizens. However, regeneration of consolidated areas is also an opportunity to improve the living conditions of the resident population, and is a necessary policy to control the expansion of the city and reduce the need for transportation, thus promoting more sustainable cities. Assuming that the governance of urban regeneration processes is key to the final outcome of the plans and determines the resulting city model, the goal of this research is to verify whether urban regeneration is necessarily a value extraction mechanism or if it can improve the quality of life in cities through citizens’ participation. It proposes a framework for analysis of decision-making in urban regeneration processes and their impact on the results of the plans, taking as a case study the city of Boston, which since the 1990s is trying to become a "city of neighborhoods", encouraging citizen participation, while seeking to position itself in the global economic scene. The analysis focuses on two redevelopment plans initiated in the late 1990s. The Jackson Square case allows us to understand the role of civil society and the third sector in the regeneration of disadvantaged neighborhoods, in a clear example of bottom-up planning. On the contrary, the conversion of the South Boston waterfront to build the Innovation District takes us to the big redevelopment efforts with economic stimulus’ goals, traditionally linked to downtowns and led by government and economic elites (the local “growth machine”) through more technocratic processes (top-down planning). The research is based on a qualitative analysis of the processes of decision making and the relationship between those involved, as well as the evaluation of the implementation of those decisions and their influence on the resulting urban model. The analysis suggests that the governance of urban regeneration processes decisively influences the outcome of interventions; however, community engagement in the decision-making process is not enough for the result of the urban regeneration to counteract the effects of neoliberalization, especially if it is limited to the planning phase and does not extend to the implementation of the projects, and if it is not supported by a broader political mobilization to ensure a redistributive public action. Moreover, urban regeneration processes redefine the urban model, since the choice of intervention areas has important consequences for the territorial balance of the city. The results of this study have implications for the discipline of urban planning. On the one hand, it confirms the validity of the "negotiated planning" paradigm, albeit under public leadership discourse and without a direct appeal to the leadership role of the private sector. On the other hand, collaborative planning in a context of "responsibilization" of community based organizations can deactivate the political power of citizen participation and serve as a "buffer" towards the local government. Furthermore, the replacement of comprehensive planning, as a tool for defining the city's future, by an opportunistic planning based on intervention in strategic areas that are supposed to induce change in the rest of the city, does not allow a coherent and consensual urban model that is collectively desired, nor it allows to use planning as a redistribution mechanism.

Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy

It has long been assumed that HIV-1 evolution is best described by deterministic evolutionary models because of the large population size. Recently, however, it was suggested that the effective population size (Ne) may be rather small, thereby allowing chance to influence evolution, a situation best described by a stochastic evolutionary model. To gain experimental evidence supporting one of the evolutionary models, we investigated whether the development of resistance to the protease inhibitor ritonavir affected the evolution of the env gene. Sequential serum samples from five patients treated with ritonavir were used for analysis of the protease gene and the V3 domain of the env gene. Multiple reverse transcription–PCR products were cloned, sequenced, and used to construct phylogenetic trees and to calculate the genetic variation and Ne. Genotypic resistance to ritonavir developed in all five patients, but each patient displayed a unique combination of mutations, indicating a stochastic element in the development of ritonavir resistance. Furthermore, development of resistance induced clear bottleneck effects in the env gene. The mean intrasample genetic variation, which ranged from 1.2% to 5.7% before treatment, decreased significantly (P < 0.025) during treatment. In agreement with these findings, Ne was estimated to be very small (500–15,000) compared with the total HIV-1 RNA copy number. This study combines three independent observations, strong population bottlenecking, small Ne, and selection of different combinations of protease-resistance mutations, all of which indicate that HIV-1 evolution is best described by a stochastic evolutionary model.

From patterns to processes: Phase and density dependencies in the Canadian lynx cycle

Across the boreal forest of North America, lynx populations undergo 10-year cycles. Analysis of 21 time series from 1821 to the present demonstrates that these fluctuations are generated by nonlinear processes with regulatory delays. Trophic interactions between lynx and hares cause delayed density-dependent regulation of lynx population growth. The nonlinearity, in contrast, appears to arise from phase dependencies in hunting success by lynx through the cycle. Using a combined approach of empirical, statistical, and mathematical modeling, we highlight how shifts in trophic interactions between the lynx and the hare generate the nonlinear process primarily by shifting functional response curves during the increase and the decrease phases.

Maximum likelihood estimation of a migration matrix and effective population sizes in n subpopulations by using a coalescent approach

A maximum likelihood estimator based on the coalescent for unequal migration rates and different subpopulation sizes is developed. The method uses a Markov chain Monte Carlo approach to investigate possible genealogies with branch lengths and with migration events. Properties of the new method are shown by using simulated data from a four-population n-island model and a source–sink population model. Our estimation method as coded in migrate is tested against genetree; both programs deliver a very similar likelihood surface. The algorithm converges to the estimates fairly quickly, even when the Markov chain is started from unfavorable parameters. The method was used to estimate gene flow in the Nile valley by using mtDNA data from three human populations.