Using rare mutations to estimate population divergence times: A maximum likelihood approach

In this paper we propose a method to estimate by maximum likelihood the divergence time between two populations, specifically designed for the analysis of nonrecurrent rare mutations. Given the rapidly growing amount of data, rare disease mutations affecting humans seem the most suitable candidates for this method. The estimator RD, and its conditional version RDc, were derived, assuming that the population dynamics of rare alleles can be described by using a birth–death process approximation and that each mutation arose before the split of a common ancestral population into the two diverging populations. The RD estimator seems more suitable for large sample sizes and few alleles, whose age can be approximated, whereas the RDc estimator appears preferable when this is not the case. When applied to three cystic fibrosis mutations, the estimator RD could not exclude a very recent time of divergence among three Mediterranean populations. On the other hand, the divergence time between these populations and the Danish population was estimated to be, on the average, 4,500 or 15,000 years, assuming or not a selective advantage for cystic fibrosis carriers, respectively. Confidence intervals are large, however, and can probably be reduced only by analyzing more alleles or loci.

Global air-sea flux of CO2: An estimate based on measurements of sea–air pCO2 difference

Approximately 250,000 measurements made for the pCO2 difference between surface water and the marine atmosphere, ΔpCO2, have been assembled for the global oceans. Observations made in the equatorial Pacific during El Nino events have been excluded from the data set. These observations are mapped on the global 4° × 5° grid for a single virtual calendar year (chosen arbitrarily to be 1990) representing a non-El Nino year. Monthly global distributions of ΔpCO2 have been constructed using an interpolation method based on a lateral advection–diffusion transport equation. The net flux of CO2 across the sea surface has been computed using ΔpCO2 distributions and CO2 gas transfer coefficients across sea surface. The annual net uptake flux of CO2 by the global oceans thus estimated ranges from 0.60 to 1.34 Gt-C⋅yr−1 depending on different formulations used for wind speed dependence on the gas transfer coefficient. These estimates are subject to an error of up to 75% resulting from the numerical interpolation method used to estimate the distribution of ΔpCO2 over the global oceans. Temperate and polar oceans of the both hemispheres are the major sinks for atmospheric CO2, whereas the equatorial oceans are the major sources for CO2. The Atlantic Ocean is the most important CO2 sink, providing about 60% of the global ocean uptake, while the Pacific Ocean is neutral because of its equatorial source flux being balanced by the sink flux of the temperate oceans. The Indian and Southern Oceans take up about 20% each.

A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis. The virus does not replicate efficiently in cell cultures, and it is therefore difficult to assess infection-neutralizing antibodies and to evaluate protective immunity in vitro. To study the binding of the HCV envelope to cell-surface receptors, we developed an assay to assess specific binding of recombinant envelope proteins to human cells and neutralization thereof. HCV recombinant envelope proteins expressed in various systems were incubated with human cells, and binding was assessed by flow cytometry using anti-envelope antibodies. Envelope glycoprotein 2 (E2) expressed in mammalian cells, but not in yeast or insect cells, binds human cells with high affinity (Kd approximately 10(-8) M). We then assessed antibodies able to neutralize E2 binding in the sera of both vaccinated and carrier chimpanzees, as well as in the sera of humans infected with various HCV genotypes. Vaccination with recombinant envelope proteins expressed in mammalian cells elicited high titers of neutralizing antibodies that correlated with protection from HCV challenge. HCV infection does not elicit neutralizing antibodies in most chimpanzees and humans, although low titers of neutralizing antibodies were detectable in a minority of infections. The ability to neutralize binding of E2 derived from the HCV-1 genotype was equally distributed among sera from patients infected with HCV genotypes 1, 2, and 3, demonstrating that binding of E2 is partly independent of E2 hypervariable regions. However, a mouse monoclonal antibody raised against the E2 hypervariable region 1 can partially neutralize binding of E2, indicating that at least two neutralizing epitopes, one of which is hypervariable, should exist on the E2 protein. The neutralization-of-binding assay described will be useful to study protective immunity to HCV infection and for vaccine development.

A gradient estimate to a degenerate parabolic equation with a singular absorption term: The global quenching phenomena

We prove global existence of nonnegative solutions to the one dimensional degenerate parabolic problems containing a singular term. We also show the global quenching phenomena for L1 initial datums. Moreover, the free boundary problem is considered in this paper.

Análise da aderência de práticas ágeis na cultura de startups de software: o mapeamento de práticas através do SEMAT Kernel.

Este trabalho analisa os principais métodos ágeis utilizados em empresas startup, como scrum, extreme programming, kanban e lean, isolando suas práticas e mapeando-as no Kernel do SEMAT para escolher os elementos essenciais da engenharia de software que estão relacionados a cada prática de forma independente. Foram identificadas 34 práticas que foram reduzidas a um conjunto de 26 pelas similaridades. Um questionário foi desenvolvido e aplicado no ambiente de startups de software para a avaliação do grau de utilização de cada determinada prática. Através das respostas obtidas foi possível a identificação de um subconjunto de práticas com utilização acima de 60% onde todos os elementos essenciais da engenharia de software são atendidos, formando um conjunto mínimo de práticas capazes de sustentar este tipo específico de ambiente.

An integral security kernel

As the user base of the Internet has grown tremendously, the need for secure services has increased accordingly. Most secure protocols, in digital business and other fields, use a combination of symmetric and asymmetric cryptography, random generators and hash functions in order to achieve confidentiality, integrity, and authentication. Our proposal is an integral security kernel based on a powerful mathematical scheme from which all of these cryptographic facilities can be derived. The kernel requires very little resources and has the flexibility of being able to trade off speed, memory or security; therefore, it can be efficiently implemented in a wide spectrum of platforms and applications, either software, hardware or low cost devices. Additionally, the primitives are comparable in security and speed to well known standards.

Use of an Inverse Method for Time Series to Estimate the Dynamics of and Management Strategies for the Box Jellyfish Carybdea marsupialis

Frequently, population ecology of marine organisms uses a descriptive approach in which their sizes and densities are plotted over time. This approach has limited usefulness for design strategies in management or modelling different scenarios. Population projection matrix models are among the most widely used tools in ecology. Unfortunately, for the majority of pelagic marine organisms, it is difficult to mark individuals and follow them over time to determine their vital rates and built a population projection matrix model. Nevertheless, it is possible to get time-series data to calculate size structure and densities of each size, in order to determine the matrix parameters. This approach is known as a “demographic inverse problem” and it is based on quadratic programming methods, but it has rarely been used on aquatic organisms. We used unpublished field data of a population of cubomedusae Carybdea marsupialis to construct a population projection matrix model and compare two different management strategies to lower population to values before year 2008 when there was no significant interaction with bathers. Those strategies were by direct removal of medusae and by reducing prey. Our results showed that removal of jellyfish from all size classes was more effective than removing only juveniles or adults. When reducing prey, the highest efficiency to lower the C. marsupialis population occurred when prey depletion affected prey of all medusae sizes. Our model fit well with the field data and may serve to design an efficient management strategy or build hypothetical scenarios such as removal of individuals or reducing prey. TThis This sdfsdshis method is applicable to other marine or terrestrial species, for which density and population structure over time are available.

Aid decision algorithms to estimate the risk in congenital heart surgery

Background and objective: In this paper, we have tested the suitability of using different artificial intelligence-based algorithms for decision support when classifying the risk of congenital heart surgery. In this sense, classification of those surgical risks provides enormous benefits as the a priori estimation of surgical outcomes depending on either the type of disease or the type of repair, and other elements that influence the final result. This preventive estimation may help to avoid future complications, or even death. Methods: We have evaluated four machine learning algorithms to achieve our objective: multilayer perceptron, self-organizing map, radial basis function networks and decision trees. The architectures implemented have the aim of classifying among three types of surgical risk: low complexity, medium complexity and high complexity. Results: Accuracy outcomes achieved range between 80% and 99%, being the multilayer perceptron method the one that offered a higher hit ratio. Conclusions: According to the results, it is feasible to develop a clinical decision support system using the evaluated algorithms. Such system would help cardiology specialists, paediatricians and surgeons to forecast the level of risk related to a congenital heart disease surgery.

Estimate for shutters for Harvard Hall, [ca. 1806]

Itemized list of cost estimates for shutters for Harvard Hall, compiled circa 1806. Includes supplies needed to install shutters for 24 windows in Harvard Hall. Materials needed include boards, nails, and cross corner hinges.

Estimate to make medical rooms, 26 June 1809

Includes estimates to alter Holden Chapel to accommodate medical classes. Alterations in the $131.50 estimate include building circular seats and installing additional shelves.

From J. Hunnewell with estimate of repairing Massachusetts Hall, [ca. 1790]

In this letter, J. Hunnewell writes President Willard with estimates for a new roof for Massachusetts Hall. Hunnewell enclosed estimated costs from both a carpenter and a mason for slate and composition roofs. Estimates include supply and labor costs.

J.[ohn] Warland's estimate for Massachusetts Hall, 20 July 1802

Includes mason John Warland's estimate for adding another storey to Massachusetts Hall, plastering several of the rooms, and the securing the necessary materials for the construction.

Estimate of expense of repairs of Massachusetts by [John] Walton and [Josiah] Moore, 13 January 1806

Includes estimate from Walton & Moore for adding another storey to Massachusetts Hall, replacing the roof, replacing glass, and painting the interior.

Mr. [Levi] Colburn's estimate, 14 April 1813

In this letter from Levi Colburn to Loammi Baldwin, Colburn details the cost estimates in dollars for the roof, floors, windows, and labor of University Hall.