The dawn of mathematical biology

In this paper I describe the early development of the so-called mathematical biophysics, as conceived by Nicolas Rashevsky back in the 1920's, as well as his latter idealization of a "relational biology". I also underline that the creation of the journal "The Bulletin of Mathematical Biophysics" was instrumental in legitimating the efforts of Rashevsky and his students, and I finally argue that his pioneering efforts, while still largely unacknowledged, were vital for the development of important scientific contributions, most notably the McCulloch-Pitts model of neural networks.Comment: 9 pages, without figure

Big Data and Deep Learning Models

Although deep learning has historically deep roots, with regard to the vast area of​ artificial intelligence and, more specifically, to the study of machine learning and artificial neural networks, it is only recently that this line of investigation has developed fruits with great commercial value, starting to have thus a significant impact on society. It is precisely because of the wide applicability of this technology nowadays that we must be alert, in order to be able to foresee the negative implications of its indiscriminate uses. Of fundamental importance, in this context, are the risks associated with collecting large amounts of data for training neural networks (and for other purposes too), the dilemma of the strong opacity of these systems, and issues related to the misuse of already trained neural networks, as exemplified by the recent proliferation of deepfakes. This text introduces and discusses these issues with a pedagogical bias, thus aiming to make the topic accessible to new researchers interested in this area of​ application of scientific models

The dawn of mathematical biology

In this paper I describe the early development of the so-called mathematical biophysics, as conceived by Nicolas Rashevsky back in the 1920´s, as well as his latter idealization of a “relational biology”. I also underline that the creation of the journal The Bulletin of Mathematical Biophysics was instrumental in legitimating the efforts of Rashevsky and his students, and I finally argue that his pioneering efforts, while still largely unacknowledged, were vital for the development of important scientific contributions, most notably the McCulloch-Pitts model of neural networks

Complexidade e organização biológica

A área de pesquisa conhecida como biologia relacional foi inaugurada por Nicolas Rashevsky, porém foi largamente desenvolvida por Robert Rosen. Neste artigo eu apresento e discuto alguns dos pressupostos subjacentes a essa linha de investigação, adotando a estratégia de focar apenas em alguns dos principais avanços propostos por Rosen, em particular aqueles vinculados às noções de complexidade e organização biológica. Enfatizo também o conceito de “fechamento causal” roseniano, devido à sua relação próxima com a noção de autopoiese de Maturana e Varela. Procuro desenvolver, da melhor forma possível, uma investigação imparcial, apontando tanto as virtudes quanto os pontos críticos dos tópicos por mim selecionados a partir da vasta obra intelectual de Rosen

Complexidade e organização biológica

A área de pesquisa conhecida como biologia relacional foi inaugurada por Nicolas Rashevsky, porém foi largamente desenvolvida por Robert Rosen. Neste artigo eu apresento e discuto alguns dos pressupostos subjacentes a essa linha de investigação, adotando a estratégia de focar apenas em alguns dos principais avanços propostos por Rosen, em particular aqueles vinculados às noções de complexidade e organização biológica. Enfatizo também o conceito de “fechamento causal” roseniano, devido à sua relação próxima com a noção de autopoiese de Maturana e Varela. Procuro desenvolver, da melhor forma possível, uma investigação imparcial, apontando tanto as virtudes quanto os pontos críticos dos tópicos por mim selecionados a partir da vasta obra intelectual de Rosen

Prophylaxis in hemophilia

Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis – the regular administration of therapeutic products to maintain hemostasis and prevent bleeding – is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs

Epidemiological characteristics of hemophilia in the pre-primary prophylaxis era: a historical cohort

Introduction: Epidemiological studies on hemophilia in the Brazilian population are historically scarce. Despite the continuous effort made by the National Program of Inherited Bleeding Disorders to map this condition, little information is available, especially on the period prior to program conception. Therefore, the present study aims to assess the epidemiological, serological, and clinical characteristics of patients with hemophilia in the state of Rio Grande do Sul, Brazil. Methods: A total of 455 patients had their medical records reviewed from January 1, 2003 to December 31, 2007. Results: We observed a remarkable prevalence of hepatitis C virus (HCV) infection in patients with both hemophilia A and B, and this prevalence significantly increased along with age (p < 0.001). No positive anti-HCV results were observed among children younger than 5 years old. There was a significant correlation between the severity of hemophilia and the number of arthropathies in all age categories. Considering the presence of inhibitors, a significant difference was observed between age groups, as older patients had higher inhibitor titers. There was a significant correlation between mean coagulation factor consumption and the number of arthropathies in patients over 5 years old. Conclusions: This profile analysis of patients with hemophilia reflects a gradual improvement in treatment safety and efficiency, as well as the need for continued investment in this population

Hemophilia: a biography on therapeutical approaches

The history of hemophilia is ancient, with descriptions dated to the 2nd century AD. The first modern narratives appeared in 1800s, when total blood transfusion was the only available treatment and life expectancy was remarkably low. Advances occurred with the use of plasma and cryoprecipitate, but only the discovered of factor concentrates revolutionized the treatment. The implantation of prophylaxis allowed hemophilic patients to prevent bleeding and the development of chronic arthropathy, although with a significant burdensome with the regular infusions. In the past 20 years, this field has witnessed major improvements, including the development of gene therapy and other pharmacological approaches

Prophylaxis in Hemophilia

Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis – the regular administration of therapeutic products to maintain hemostasis and prevent bleeding – is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs

Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting

TALENs are important new tools for genome engineering. Fusions of transcription activator-like (TAL) effectors of plant pathogenic Xanthomonas spp. to the FokI nuclease, TALENs bind and cleave DNA in pairs. Binding specificity is determined by customizable arrays of polymorphic amino acid repeats in the TAL effectors. We present a method and reagents for efficiently assembling TALEN constructs with custom repeat arrays. We also describe design guidelines based on naturally occurring TAL effectors and their binding sites. Using software that applies these guidelines, in nine genes from plants, animals and protists, we found candidate cleavage sites on average every 35 bp. Each of 15 sites selected from this set was cleaved in a yeast-based assay with TALEN pairs constructed with our reagents. We used two of the TALEN pairs to mutate HPRT1 in human cells and ADH1 in Arabidopsis thaliana protoplasts. Our reagents include a plasmid construct for making custom TAL effectors and one for TAL effector fusions to additional proteins of interest. Using the former, we constructed de novo a functional analog of AvrHah1 of Xanthomonas gardneri. The complete plasmid set is available through the non-profit repository AddGene and a web-based version of our software is freely accessible online