The International Law of Colonialism in East Africa: Germany, England, and the Doctrine of Discovery

The non-European, non-Christian world was colonized under international law that is known today as the Doctrine of Discovery. This common-law international Doctrine was codified into European international law at the Berlin Conference of 1884–85 and in the Berlin Act of 1885 specifically to partition and colonize Africa. Thirteen European countries and the United States attended the four-month Conference, which ended with thirteen countries signing the Berlin Act on February 26, 1885. Under the Discovery Doctrine and the Berlin Act, these European countries claimed superior rights over African nations and Indigenous Peoples. European explorers planted crosses, signed hundreds of treaties, and raised flags in many parts of Africa to make legal claims of ownership and domination over the native nations and peoples, and their lands and assets. These claims were justified in the fifteenth and in the nineteenth centuries by racial, ethnocentric, and religious ideas about the alleged superiority of European Christian nations. This Article examines the application of the Doctrine and the Berlin Act by England and Germany in East Africa, which now comprises Kenya, Uganda, and Tanzania. This comparative law analysis demonstrates convincingly that the Berlin Act and these colonizing countries applied what we define as the ten elements of the Doctrine of Discovery. These elements had been developed and refined by European legal and political systems since the mid-1400s. Over 400 years later, the Berlin Conference of 1884–85 expressly and implicitly adopted and codified all ten elements to control the European partition and colonization of Africa. Germany and England used this international law to colonize East Africa. Needless to say, European domination, exploitation, and colonization seriously injured the human, property, sovereign, and self-determination rights of Indigenous nations and peoples. The effects of colonization are still felt today. The comparative legal analysis set out in this article sheds light on how law affected and directed African colonization. It also develops a better understanding of the international law of colonialism as well as its historical process and impacts. This Article concludes by explaining the crucial importance of this knowledge

Screening of retroviral cDNA libraries for factors involved in protein phosphorylation in signaling cascades

We report a novel approach that allows for the rapid identification of proteins mediating phosphorylation in signaling cascades after specific stimulation. As a proof of concept, we used the interferon- γ (IFN-γ)-induced phosphorylation of signal transducer and activator of transcription-1 (Stat1) in a human promonocytic cell line, which was previously shown to be deficient in this signaling pathway. By using retroviral cDNA expression libraries, transduced selector cells expressing single cDNAs were stimulated with IFN-γ, then fixed, permeabilized and stained intracellularly for phospho-Stat1 levels. Cells responding to the stimulation, which showed increased levels of phosphorylated Stat1, were enriched using fluorescence activated cell sorting (FACS). Genomic DNA was isolated from the enriched cell population and served as a template for cDNA amplification using PCR. After only one round of selection, a cDNA encoding the β-chain of the IFN-γ receptor (IFNGR2) was obtained and demonstrated to restore the selected phenotype. The approach now allows one to use phospho-events as reporters, alone or in tandem, for screening of signaling network states, overcoming a prior need to rely on the reporter genes that are often only indirect measures of phenotypes desired in a screen

Fusoselect: cell-cell fusion activity engineered by directed evolution of a retroviral glycoprotein

Membrane fusion plays a key role in many biological processes including vesicle trafficking, synaptic transmission, fertilization or cell entry of enveloped viruses. As a common feature the fusion process is mediated by distinct membrane proteins. We describe here ‘Fusoselect', a universal procedure allowing the identification and engineering of molecular determinants for cell-cell fusion-activity by directed evolution. The system couples cell-cell fusion with the release of retroviral particles, but can principally be applied to membrane proteins of non-viral origin as well. As a model system, we chose a γ-retroviral envelope protein, which naturally becomes fusion-active through proteolytic processing by the viral protease. The selection process evolved variants that, in contrast to the parental protein, mediated cell-cell fusion in absence of the viral protease. Detailed analysis of the variants revealed molecular determinants for fusion competence in the cytoplasmic tail (CT) of retroviral Env proteins and demonstrated the power of Fusoselec

Fusoselect: cell–cell fusion activity engineered by directed evolution of a retroviral glycoprotein

Membrane fusion plays a key role in many biological processes including vesicle trafficking, synaptic transmission, fertilization or cell entry of enveloped viruses. As a common feature the fusion process is mediated by distinct membrane proteins. We describe here ‘Fusoselect’, a universal procedure allowing the identification and engineering of molecular determinants for cell–cell fusion-activity by directed evolution. The system couples cell–cell fusion with the release of retroviral particles, but can principally be applied to membrane proteins of non-viral origin as well. As a model system, we chose a γ-retroviral envelope protein, which naturally becomes fusion-active through proteolytic processing by the viral protease. The selection process evolved variants that, in contrast to the parental protein, mediated cell–cell fusion in absence of the viral protease. Detailed analysis of the variants revealed molecular determinants for fusion competence in the cytoplasmic tail (CT) of retroviral Env proteins and demonstrated the power of Fusoselect

GiViP: A Visual Profiler for Distributed Graph Processing Systems

Analyzing large-scale graphs provides valuable insights in different application scenarios. While many graph processing systems working on top of distributed infrastructures have been proposed to deal with big graphs, the tasks of profiling and debugging their massive computations remain time consuming and error-prone. This paper presents GiViP, a visual profiler for distributed graph processing systems based on a Pregel-like computation model. GiViP captures the huge amount of messages exchanged throughout a computation and provides an interactive user interface for the visual analysis of the collected data. We show how to take advantage of GiViP to detect anomalies related to the computation and to the infrastructure, such as slow computing units and anomalous message patterns.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Structural organization of mammalian prions as probed by limited proteolysis

Elucidation of the structure of PrP(Sc) continues to be one major challenge in prion research. The mechanism of propagation of these infectious agents will not be understood until their structure is solved. Given that high resolution techniques such as NMR or X-ray crystallography cannot be used, a number of lower resolution analytical approaches have been attempted. Thus, limited proteolysis has been successfully used to pinpoint flexible regions within prion multimers (PrP(Sc)). However, the presence of covalently attached sugar antennae and glycosylphosphatidylinositol (GPI) moieties makes mass spectrometry-based analysis impractical. In order to surmount these difficulties we analyzed PrP(Sc) from transgenic mice expressing prion protein (PrP) lacking the GPI membrane anchor. Such animals produce prions that are devoid of the GPI anchor and sugar antennae, and, thereby, permit the detection and location of flexible, proteinase K (PK) susceptible regions by Western blot and mass spectrometry-based analysis. GPI-less PrP(Sc) samples were digested with PK. PK-resistant peptides were identified, and found to correspond to molecules cleaved at positions 81, 85, 89, 116, 118, 133, 134, 141, 152, 153, 162, 169 and 179. The first 10 peptides (to position 153), match very well with PK cleavage sites we previously identified in wild type PrP(Sc). These results reinforce the hypothesis that the structure of PrP(Sc) consists of a series of highly PK-resistant β-sheet strands connected by short flexible PK-sensitive loops and turns. A sizeable C-terminal stretch of PrP(Sc) is highly resistant to PK and therefore perhaps also contains β-sheet secondary structure

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice

Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories