305 research outputs found

    Mass legal executions in America up to 1865

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    Through recorded history, governments have executed persons, sometimes in groups for the same offense. In the United States, most post trial mass executions, defined as executing four or more persons for the same incident, occurred prior to 1866. This unstudied aspect of capital punishment is interesting for what it tells us about the social climate of the era (colonial days through the end of the American Civil War) in which those executions occurred and the leading fears of the society and/or its leaders. Following the American Civil War, mass executions not only declined in number and rate, but also matched more the trends in capital punishment overall. A detailed list of mass legal executions in America up to 1865 is appended to this article.Les archives montrent que tout au long de l’histoire, les gouvernements ont pratiqué la peine de mort, et ce parfois collectivement. Aux États-Unis, la plupart des exécutions judiciaires de masse – entendues comme la mise à mort de quatre personnes au moins pour un même crime – sont survenues avant 1866. Cet aspect inexploré de la peine capitale est intéressant pour ce qu’il nous révèle du climat social de l’époque (de la période coloniale à la fin de la guerre de Sécession) des principales peurs régnant dans la société ou des craintes des dirigeants. Après la guerre de Sécession, le nombre d’exécutions de masse a décliné en nombre et en taux, se rapprochant des tendances de la peine de mort ordinaire. Une liste détaillée des exécutions judiciaires de masse jusqu’en 1865 est annexée à l’article

    Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle.

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    Asexual blood stages of the malaria parasite, which cause all the pathology associated with malaria, can readily be genetically modified by homologous recombination, enabling the functional study of parasite genes that are not essential in this part of the life cycle. However, no widely applicable method for conditional mutagenesis of essential asexual blood-stage malarial genes is available, hindering their functional analysis. We report the application of the DiCre conditional recombinase system to Plasmodium falciparum, the causative agent of the most dangerous form of malaria. We show that DiCre can be used to obtain rapid, highly regulated site-specific recombination in P. falciparum, capable of excising loxP-flanked sequences from a genomic locus with close to 100% efficiency within the time-span of a single erythrocytic growth cycle. DiCre-mediated deletion of the SERA5 3' UTR failed to reduce expression of the gene due to the existence of alternative cryptic polyadenylation sites within the modified locus. However, we successfully used the system to recycle the most widely used drug resistance marker for P. falciparum, human dihydrofolate reductase, in the process producing constitutively DiCre-expressing P. falciparum clones that have broad utility for the functional analysis of essential asexual blood-stage parasite genes

    On the interpretation of spin-polarized electron energy loss spectra

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    We study the origin of the structure in the spin-polarized electron energy loss spectroscopy (SPEELS) spectra of ferromagnetic crystals. Our study is based on a 3d tight-binding Fe model, with constant onsite Coulomb repulsion U between electrons of opposite spin. We find it is not the total density of Stoner states as a function of energy loss which determines the response of the system in the Stoner region, as usually thought, but the densities of Stoner states for only a few interband transitions. Which transitions are important depends ultimately on how strongly umklapp processes couple the corresponding bands. This allows us to show, in particular, that the Stoner peak in SPEELS spectra does not necessarily indicate the value of the exchange splitting energy. Thus, the common assumption that this peak allows us to estimate the magnetic moment through its correlation with exchange splitting should be reconsidered, both in bulk and surface studies. Furthermore, we are able to show that the above mechanism is one of the main causes for the typical broadness of experimental spectra. Finally, our model predicts that optical spin waves should be excited in SPEELS experiments.Comment: 11 pages, 7 eps figures, REVTeX fil

    Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis

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    Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings

    Molecular determinants of binding to the Plasmodium subtilisin-like protease 1.

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    PfSUB1, a subtilisin-like protease of the human malaria parasite Plasmodium falciparum, is known to play important roles during the life cycle of the parasite and has emerged as a promising antimalarial drug target. In order to provide a detailed understanding of the origin of binding determinants of PfSUB1 substrates, we performed molecular dynamics simulations in combination with MM-GBSA free energy calculations using a homology model of PfSUB1 in complex with different substrate peptides. Key interactions, as well as residues that potentially make a major contribution to the binding free energy, are identified at the prime and nonprime side of the scissile bond and comprise peptide residues P4 to P2'. This finding stresses the requirement for peptide substrates to interact with both prime and nonprime side residues of the PfSUB1 binding site. Analyzing the energetic contributions of individual amino acids within the peptide-PfSUB1 complexes indicated that van der Waals interactions and the nonpolar part of solvation energy dictate the binding strength of the peptides and that the most favorable interactions are formed by peptide residues P4 and P1. Hot spot residues identified in PfSUB1 are dispersed over the entire binding site, but clustered areas of hot spots also exist and suggest that either the S4-S2 or the S1-S2' binding site should be exploited in efforts to design small molecule inhibitors. The results are discussed with respect to which binding determinants are specific to PfSUB1 and, therefore, might allow binding selectivity to be obtained

    Responsible management: Engaging moral reflexive practice through threshold concepts

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    YesIn this conceptual paper we argue that, to date, principles of responsible management have not impacted practice as anticipated because of a disconnect between knowledge and practice. This disconnect means that an awareness of ethical concerns, by itself, does not help students take personal responsibility for their actions. We suggest that an abstract knowledge of principles has to be supplemented by an engaged understanding of the responsibility of managers and leaders to actively challenge irresponsible practices. We argue that a form of moral reflexive practice drawing on an understanding of threshold concepts is central to responsible management, and provides a gateway to transformative learning. Our conceptual argument leads to implications for management and professional education

    Multi-site assessment of the precision and reproducibility of multiple reaction monitoring–based measurements of proteins in plasma

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    Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low µg/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma
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