Moral, ethical and human rights arguments for using experimental and clinically unproven drugs to combat the Ebola Virus Disease

This article discusses and considers the arguments in favour of using clinically unproven medicine in the fight against terminal diseases, with specific reference to the Ebola Virus Disease (EVD) in Africa. In particular, this proposition is supported from a moral, ethical and human rights-based approach. To this end, two philosophical foundations are considered, namely the utilitarian theory of morality and the rights-based approach. Furthermore, emphasis is placed on the role of African leadership in putting in place best and co- ordinated measures to combat EVD. An analysis of the use of clinically untested or unproven drugs is articulated by analysing the famous American case of Abigail Alliance for Better Access to Developmental Drugs. From a utilitarian perspective, access to unproven drugs may only be morally and ethically justified if it will positively combat EVD. In terms of the rights-based approach, access must be in the public interest and should not violate the rights of other persons. After considering scholarship that argues for and against the creation of a constitutionally guaranteed right of access to unproven drugs, it is concluded that a delicate balancing of all relevant issues is not as easy as it appears. Nevertheless, the article recommends that African governments leverage the 2014 statement by the WHO that it is ethical to use untested drugs subject to meeting certain conditions in their efforts to combat EVD

Content Analysis of Ethics of Governance, Maladministration and Political Corruption

Although different forms of corruption exist in every regions, Africa, South America, Latin America, Russia, and Asia countries, perhaps to a greater extent engage in higher levels of corruption more than other regions of the world. Applying ethics of governance and theory of “Patrimonialism”, this article examines governance of ethics and corruption. This article argues that corruption lays the foundation for the abridgement of citizens’ rights and perpetuation of underdevelopment. Methodologically, we explored contents through multiple media sources, ensuring rigor and trustworthiness. Our findings reveal how corruption is being perpetuated in Nigeria, prosecuted and the challenges. This article finds a strong relationship between corruption, the absence of ethics of governance, and maladministration. Many public and political office holders engage or support corruption, there is lack of moral and ethical considerations. More so, it appears that politics is based on wealth acquisition, self-interest rather than on ideologies

Men's nutrition knowledge is important for women's and children's nutrition in Ethiopia.

In an effort to address undernutrition among women and children in rural areas of low-income countries, nutrition-sensitive agriculture (NSA) and behaviour change communication (BCC) projects heavily focus on women as an entry point to effect nutritional outcomes. There is limited evidence on the role of men's contribution in improving household diets. In this Agriculture to Nutrition trial (Clinicaltrials.gov identifier: NCT03152227), we explored associations between men's and women's nutritional knowledge on households', children's and women's dietary diversity. At the midline evaluation conducted in July 2017, FAO's nutrition knowledge questionnaire was administered to male and female partners in 1396 households. There was a high degree of agreement (88%) on knowledge about exclusive breastfeeding between parents; however, only 56-66% of the households had agreement when comparing knowledge of dietary sources of vitamin A or iron. Factor analysis of knowledge dimensions resulted in identifying two domains, namely, 'dietary' and 'vitamin' knowledge. Dietary knowledge had a larger effect on women's and children's dietary diversities than vitamin knowledge. Men's dietary knowledge had strong positive associations with households' dietary diversity scores (0.24, P value = 0.001), children's dietary diversity (0.19, P value = 0.008) and women's dietary diversity (0.18, P value < 0.001). Distance to markets and men's education levels modified the effects of nutrition knowledge on dietary diversity. While previous NSA and BCC interventions predominantly focused on uptake among women, there is a large gap and strong potential for men's engagement in improving household nutrition. Interventions that expand the role of men in NSA may synergistically improve household nutrition outcomes

MasakhaNER 2.0: Africa-centric Transfer Learning for Named Entity Recognition

African languages are spoken by over a billion people, but are underrepresented in NLP research and development. The challenges impeding progress include the limited availability of annotated datasets, as well as a lack of understanding of the settings where current methods are effective. In this paper, we make progress towards solutions for these challenges, focusing on the task of named entity recognition (NER). We create the largest human-annotated NER dataset for 20 African languages, and we study the behavior of state-of-the-art cross-lingual transfer methods in an Africa-centric setting, demonstrating that the choice of source language significantly affects performance. We show that choosing the best transfer language improves zero-shot F1 scores by an average of 14 points across 20 languages compared to using English. Our results highlight the need for benchmark datasets and models that cover typologically-diverse African languages

Mining protein loops using a structural alphabet and statistical exceptionality

<p>Abstract</p> <p>Background</p> <p>Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied.</p> <p>Results</p> <p>We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 Å). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of amino-acid conservation with at least four significant positions and 87% of long loops contain at least one such word. We complement our analysis with the detection of statistically over-represented patterns of structural letters as in conventional DNA sequence analysis. About 30% (930) of structural words are over-represented, and cover about 40% of loop lengths. Interestingly, these words exhibit lower structural variability and higher sequential specificity, suggesting structural or functional constraints.</p> <p>Conclusions</p> <p>We developed a method to systematically decompose and study protein loops using recurrent structural motifs. This method is based on the structural alphabet HMM-SA and not on structural alignment and geometrical parameters. We extracted meaningful structural motifs that are found in both short and long loops. To our knowledge, it is the first time that pattern mining helps to increase the signal-to-noise ratio in protein loops. This finding helps to better describe protein loops and might permit to decrease the complexity of long-loop analysis. Detailed results are available at <url>http://www.mti.univ-paris-diderot.fr/publication/supplementary/2009/ACCLoop/</url>.</p

Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ

The recently characterised 299-residue human XLF/Cernunnos protein plays a crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts with the XRCC4–DNA Ligase IV complex. Here, we report the crystal structure of the XLF (1–233) homodimer at 2.3 Å resolution, confirming the predicted structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a short distorted four helical bundle and a C-terminal helical structure wedged between the coiled-coil and head domain. The existence of a dimer as the major species is confirmed by size-exclusion chromatography, analytical ultracentrifugation, small-angle X-ray scattering and other biophysical methods. We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4 by surface plasmon resonance and analyse these in terms of surface properties, amino-acid conservation and mutations in immunodeficient patients. Our data are most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV complex

Numerical study of nonlinear heat transfer from a wavy surface to a high permeability medium with pseudo-spectral and smoothed particle methods

Motivated by petro-chemical geological systems, we consider the natural convection boundary layer flow from a vertical isothermal wavy surface adjacent to a saturated non-Darcian high permeability porous medium. High permeability is considered to represent geologically sparsely packed porous media. Both Darcian drag and Forchheimer inertial drag terms are included in the velocity boundary layer equation. A high permeability medium is considered. We employ a sinusoidal relation for the wavy surface. Using a set of transformations, the momentum and heat conservation equations are converted from an (x, y) coordinate system to an (x,η) dimensionless system. The two-point boundary value problem is then solved numerically with a pseudo-spectral method based on combining the Bellman–Kalaba quasi linearization method with the Chebyschev spectral collocation technique (SQLM). The SQLM computations are demonstrated to achieve excellent correlation with smoothed particle hydrodynamic (SPH) Lagrangian solutions. We study the effect of Darcy number (Da), Forchheimer number (Fs), amplitude wavelength (A) and Prandtl number (Pr) on the velocity and temperature distributions in the regime. Local Nusselt number is also computed for selected cases. The study finds important applications in petroleum engineering and also energy systems exploiting porous media and undulating (wavy) surface geometry. The SQLM algorithm is shown to be exceptionally robust and achieves fast convergence and excellent accuracy in nonlinear heat transfer simulations

Highly Precise and Developmentally Programmed Genome Assembly in Paramecium Requires Ligase IV–Dependent End Joining

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5′ overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi–mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5′-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3′ ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a “cut-and-close” mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics