Preparative and analytical methods developed by separation scientists have played an important role in the history of molecular biology. One such early method is gel electrophoresis, a technique that uses various types of gel as its supporting medium to separate charged molecules based on size and other properties. Historians of science, however, have only recently begun to pay closer attention to this material epistemological dimension of biomolecular science. This paper substantiates the historiographical thread that explores the relationship between modern (...) laboratory practice and the production of scientific knowledge. It traces the historical development of gel electrophoresis from the mid-1940s to the mid-1960s, with careful attention to the interplay between technical developments and disciplinary shifts, especially the rise of molecular biology in this time-frame. Claiming that the early 1950s marked a decisive shift in the evolution of electrophoretic methods from moving boundary to zone electrophoresis, I reconstruct various trajectories in which scientists such as Oliver Smithies sought out the most desirable solid supporting medium for electrophoretic instrumentation. Biomolecular knowledge, I argue, emerged in part from this process of seeking the most appropriate supporting medium that allowed for discrete molecular separation and visualization. The early 1950s, therefore, marked not only an important turning point in the history of separation science, but also a transformative moment in the history of the life sciences as the growth of molecular biology depended in part on the epistemological access to the molecular realm available through these evolving technologies. (shrink)

Preparative and analytical methods developed by separation scientists have played an important role in the history of molecular biology. One such early method is gel electrophoresis, a technique that uses various types of gel as its supporting medium to separate charged molecules based on size and other properties. Historians of science, however, have only recently begun to pay closer attention to this material epistemological dimension of biomolecular science. This paper substantiates the historiographical thread that explores the relationship between modern (...) laboratory practice and the production of scientific knowledge. It traces the historical development of gel electrophoresis from the mid-1940s to the mid-1960s, with careful attention to the interplay between technical developments and disciplinary shifts, especially the rise of molecular biology in this time-frame. Claiming that the early 1950s marked a decisive shift in the evolution of electrophoretic methods from moving boundary to zone electrophoresis, I reconstruct various trajectories in which scientists such as Oliver Smithies sought out the most desirable solid supporting medium for electrophoretic instrumentation. Biomolecular knowledge, I argue, emerged in part from this process of seeking the most appropriate supporting medium that allowed for discrete molecular separation and visualization. The early 1950s, therefore, marked not only an important turning point in the history of separation science, but also a transformative moment in the history of the life sciences as the growth of molecular biology depended in part on the epistemological access to the molecular realm available through these evolving technologies. (shrink)

Intensive research and development of electrophoresis methodology and instrumentation during past decades has resulted in unique methods widely implemented in bioanalysis. While two‐dimensional electrophoresis and denaturing polyacrylamide gel electrophoresis in sodium dodecylsulfate are still the most frequently used electrophoretic methods applied to analyses of proteins, new miniaturized capillary and microfluidic versions of electromigrational methods have been developed. High‐throughput electrophoretic instruments with hundreds of capillaries for parallel separations and laser‐induced fluorescence detection of labeled DNA strands have been of (...) key importance for the scientific and commercial success of the Human Genome Project. Another powerful method, capillary isoelectric focusing with pressurized and pH‐driven mobilization, provides efficient separations and on‐line sensitive detection of proteins, bacteria and viruses. Electrophoretic microfluidic devices can integrate single‐cell injection, cell lysis, separation of its components and fluorescence or mass spectrometry detection. These miniaturized devices also proved the capability of single‐molecule detection. (shrink)

For many years, there has been a gap in our capacity to study the structure and organization of chromosomal DNA molecules. The very small genomes of some viruses and bacteriophages (≤ 50,000 bp or 50 kb) are amenable to analysis by conventional gel electrophoresis, while the extremely large DNA molecules (> 100,000 kb) comprising the chromosomes of higher eukaryotes have been analysed under the light microscope, using a range of banding and in situ hybridization techniques. However, intact DNA molecules (...) with sizes between these two extremes have been largely inaccessible experimentally. This gap has recently been bridged with the development of two‐dimensional electrophoretic procedures that allow the separation and purification of chromosome‐sized DNA molecules ranging from ∼ 50 kb to several thousand kb.1–3 There are currently two variations of the technique in use: pulsed field gradient (PFG) gel electrophoresis1,2 and orthogonal‐field‐alteration gel electrophoresis (OFAGE).3 Both are based on a common principle, differing primarily in the geometry of the electrodes. Already, they have been employed to determine the approximate chromosome sizes and numbers for a variety of lower eukaryotes, including yeast and several protozoa.2–10 These ‘molecular karyotypes’ provide fundamental information about the genomic organization of each organism, and allow very rapid construction of linkage maps. Surprisingly, they have also revealed a remarkable plasticity in the genomes of several lower eukaryotes. (shrink)

Der Band stellt in Einzelportraits aktuelle Positionen zu einer kritischen Theorie der Demokratie sowie verschiedene Ansatze der Staatskritik von Autorinnen und Autoren der Politischen Philosophie aus Frankreich vor. Einige der hier vorgestellten Ansatze sind dem so genannten Poststrukturalismus zuzuordnen. Daruber hinaus kommt eine Reihe anderer demokratie- und staatstheoretischer Ansatze zur Sprache, insbesondere solcher Autorinnen und Autoren, die im deutschen Sprachraum (noch) nicht stark berucksichtigt werden. In den Beitragen zu den franzosischen Theoretikerinnen und Theoretikern werden deren zentrale demokratie- und staatskritische Thesen (...) dargestellt und eingehend diskutiert. Neben einem Uberblick uber die vielfaltigen gegenwartigen Debatten im franzosischsprachigen Diskurs uber Demokratietheorie und Staatskritik bietet der Band wichtige Impulse fur eine vertiefende Auseinandersetzung mit kritischer Demokratietheorie und deren Perspektiven - jenseits von Sprach- und Landesgrenzen auch auf der transnationalen und globalen Ebene. (shrink)

Responsibility in religious belief.--Religion and illusion; and religion and reality.--Progress in religion.--Preliminaries to religious belief.--The apocalyptic element in the teaching of Jesus.--The specific genius of Christianity.--What do we mean by heaven? and what do we mean by hell?--The essentials of Catholicism.--The convictions common to Catholicism and Protestantism.--Institutional Christianity.--Christianity and the supernatural.

Das Buch entwirft mithilfe von Befragungen des Politischen eine radikale und kritische politische Theorie. Hierfür ist zum einen wichtig, die derzeit vorherrschende politische Theorie und Philosophie, die auf umfassende normative Begründungsprogramme setzt, einer eingehenden Kritik zu unterziehen. Das geschieht in dieser Studie, indem die Konturen einer gesellschaftstheoretischen, kritischen und skeptischen politischen Theorie in Auseinandersetzung mit u.a. Hegel, Marx, Nietzsche, Foucault, Derrida, Lefort, Butler und Rancière ausgeleuchtet werden. Zum anderen wird das Potential dieser anderen kritischen politischen Theorie an drei grundlegenden Gegenstandsbereichen (...) erprobt: Subjektkonstitution, Gesellschaftsordnung und radikale Demokratie. (shrink)

During replication, the topology of DNA changes continuously in response to well‐known activities of DNA helicases, polymerases, and topoisomerases. However, replisomes do not always progress at a constant speed and can slow‐down and even stall at precise sites. The way these changes in the rate of replisome progression affect DNA topology is not yet well understood. The interplay of DNA topology and replication in several cases where progression of replication forks reacts differently to changes in DNA topology ahead is discussed (...) here. It is proposed, there are at least two types of replication fork barriers: those that behave also as topological barriers and those that do not. Two‐Dimensional (2D) agarose gel electrophoresis is the method of choice to distinguish between these two different types of replication fork barriers. (shrink)

Kollektive und individuelle Selbstbestimmung lassen sich in pluralistischen Gesellschaften kaum verwirklichen, ohne die Besonderheiten sozialer Gruppen zu berücksichtigen. Die Autoren fragen, wie die politische Philosophie diese Herausforderungen normativ reflektieren kann. Es wird deutlich, dass die größte Aufgabe heute darin besteht, Besonderheits- und Gleichheitsforderungen miteinander zu vermitteln.

Resumen: Analizo y critico las principales objeciones que Carlos Blanco plantea, en Las fronteras del pensamiento, contra las 5 vías de Tomás de Aquino. Mi objetivo es mostrar que dichas objeciones fallan, lo cual nos va a permitir traer, a la literatura en español, ciertas discusiones del mundo filosófico anglosajón. Palabras clave: 5 vías, Tomás de Aquino, Tomismo, Existencia de Dios, Filosofía de la religión Abstract: I analyze and critique Carlos Blanco’s main objections against Aquinas’s 5 ways, to be found (...) in his latest book, Las fronteras del pensamiento. My aim is to show how these objections miss the mark. This will allow us to bring into the Spanish literature some discussions that have taken place in the English-speaking world. Kewyords: 5 ways, Thomas Aquinas, Thomism, God’s existence, Philosophy of religion. (shrink)

En este trabajo repaso la concepción del cuerpo de Nietzsche y de Butler, intentando mostrar cómo cada una nos ayuda a superar un error de la modernidad. Nietzsche nos permite recuperar el cuerpo y contrarrestar el dualismo cartesiano, que lo valora tan poco, convirtiéndolo en una mera máquina. La obra de Judith Butler, por otro lado, especialmente Precarious Life y Frames of War, nos sirve para hacer frente al individualismo, al poner sobre la mesa la socialidad del cuerpo, el modo (...) en que nuestro cuerpo habla de los otros y está expuesto a los otros. (shrink)

This article is devoted to understanding the typological status of Tolstoy’s ideas in the context of the evolution of European humanism from the Renaissance to existentialism, from the doctrine of...

This article aims to test the hypothesis that metaphysical grounding is an instance of essentially ordered (or per se ) causation, a species of causation identified by medieval philosophers and theologians like Aquinas and Scotus, but largely forgotten from then on. The article reviews some of the consensus of grounding theorists on the nature of metaphysical grounding (or ontological dependence) compared to some of the crucial characteristics of essentially ordered causal series as articulated by scholastic and neo-Aristotelian philosophers then and (...) now. The authors emphasize their similarities, which they hold is enough to render strongly plausible the thesis that grounding is essentially ordered causation (G = EOC). Moreover, they highlight the potential benefits of this identification both for theories of grounding and EOC, especially as it concerns matters of fundamentality. Finally, they consider the limits of their hypothesis. (shrink)

​Kaum ein Konzept in der jüngeren politischen Theoriegeschichte kann auf eine solch steile und, wie sich mittlerweile gezeigt hat, auch langanhaltende Karriere zurückblicken wie das der Deliberation. Die in diesem Sammelband vereinigten Überlegungen stehen unter der zweiteiligen übergreifenden Überschrift "Deliberative Kritik – Kritik der Deliberation", die in einem Zug den kritischen Sinn der Deliberation und die Notwendigkeit einer reflexiven Kritik am Konzept der Deliberation selbst deutlich macht. Neben Erkundungen der Ideengeschichte und der normativen Grundlagen der Deliberation geht es um eine (...) Auseinandersetzung mit alternativen Konzeptionen und institutionellen Kontexten. Angesichts des Umstands, dass sich politische Prozesse bekanntlich seit geraumer Zeit aus den nationalstaatlichen Rahmungen herauslösen, werden zudem transnationale und kosmopolitische Perspektiven umfassend ausgeleuchtet. All diese topoi berühren wesentliche Denklinien der Arbeiten Rainer Schmalz-Bruns’, dem dieser Sammelband zum sechzigsten Geburtstag gewidmet ist. (shrink)

Canonical texts -- Philosophy -- Literature and History.

From the Editors:Such was the topic considered by members of a new discussion club, "The Free Word" [Svobodnoe slovo] , along with specialists from the Institute of Philosophy, USSR Academy of Sciences.

From the Editors:Such was the topic considered by members of a new discussion club, "The Free Word" [Svobodnoe slovo], along with specialists from the Institute of Philosophy, USSR Academy of Sciences.

The replicon hypothesis, first proposed in 1963 by Jacob and Brenner(1), states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an (...) assessment of their activity. Two‐dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms. (shrink)

A crucial part of the knowledge of molecular biologists is procedural knowledge, that is, knowledge of how to do things in laboratories. Procedural knowledge of molecular biologists involves both perceptual-motor skills and cognitive skills. We discuss such skills required in performing the most commonly used molecular biology techniques, namely, Polymerase Chain Reaction and gel electrophoresis. We argue that procedural knowledge involved in performing these techniques is more than just knowing their protocols. Creative exploration and experience are essential for the (...) acquisition of procedural knowledge in molecular biology. With enough experience, molecular biologists make intuitive judgments without recourse to analytical reasoning. We propose that procedural knowledge is intuitive recognition of the patterns of one's environment that are the most relevant for making a decision or acting appropriately. Finally, we argue that knowledge of molecular biologists requires an integration of procedural knowledge and propositional knowledge. (shrink)

Until quite recently, recombinant DNA technology was not able to deal with DNA molecules larger than 20–40 kb. This is a serious limitation for the study of mammalian, and in particular human genomes whose total length is approx. 3 × 106 kb, since the best resolution of genetic and chromosomal analysis is usually the rough equivalent of 1000–5000 kb. Three recently developed methods promise to bridge this gap: pulsed field gel electrophoresis, which can analyze megabase‐sized DNA fragments; cloning in (...) yeast, which can clone and propagate DNA fragments of several hundred kb; and jumping libraries, which allow ‘jumping’ over large distances along the chromosome. This review presents the current status of these very promising technologies. (shrink)

The human genome contains about 30,000 genes, each creating several transcripts per gene. Transcript structures and expression are studied by high‐throughput transcriptomic techniques using microarrays. Generally, transcripts are not directly operating molecules, but are translated into functional proteins, post‐translationally modified by proteolysis, glycosylation, phosphorylation, etc., sometimes with great functional impact. Proteins need to be analyzed by proteomic techniques, less suited for high‐throughput. Two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE), separating thousands of proteins has developed slowly over the past quarter of a (...) century. This technique is now quite reproducible and suitable for differential proteomics, comparing normal and diseased cells/tissues revealing differentially regulated proteins. 2D‐PAGE is combined with protein‐identification methods, currently mass spectrometry (MS), which has been significantly improved over the last decade. Other proteomic techniques studying protein–protein interactions are now either established or still being developed, such as peptide or protein arrays, phage display, and the yeast two‐hybrid system. The strengths and weaknesses of these techniques are discussed. BioEssays 26:901–915, 2004. © 2004 Wiley Periodicals, Inc. (shrink)