Multi-element association and regional geochemistry of protoliths in tashan jatau area, northwestern nigeria: implications for gold exploration

Soil geochemical surveys are widely used in the early stages of gold exploration, especially in areas with poor outcrops and thick overburden. Fifty-one (51) soil samples were collected in duplicate with the aim of analyzing them geochemically and determining the gold grade through panning and weighing methods. The geochemical results were subjected to multivariate statistical treatment through Factor analysis and Pearson correlation matrix. Four factors were generated from the PCA. These are Factor 1: Cu-Sr-Nb-Ba-La-W-Pb-Zr, suggesting sulfide mineralization that is related to granitic rock while Factor 2 has Au with a low to negative correlation with Mo and Nb suggesting a second phase of intrusion-related activity which must have emplaced gold in this area. Factor 3 is made up of W-Pb suggesting a second sulfide mineralization distinct from the first. While Factor 4 gives a single element factor, Hg. Single-elementt maps were constructed to show the element dispersion in the catchment. In general gold concentrations in this study is erratic and attain a high of 0.67ppm and 0.90g/t. The study delineates the northwestern part of the catchment to be the most prolific in terms of gold potential and shows that the granitic batholiths are the most primary gold-hosting lithology. &nbsp

Rational, computer-aided design of multi-target ligands

Over the past two decades the “one drug – one target – one disease” concept became the prevalent paradigm in drug discovery. The main idea of this approach is the identification of a single protein target whose inhibition leads to a successful treatment of the examined disease. The predominant assumption is that highly selective ligands would avoid unwanted side effects caused by binding to secondary non-therapeutic targets. In recent years the results of post-genomic and network biology showed that proteins rarely act in isolated systems but rather as a part of a highly connected network [1]. In addition this connectivity leads to more robust systems that cannot be interfered by the inhibition of a single target of that network and consequently might not lead to the desired therapeutic effect [2]. Furthermore studies prove that robust systems are rather affected by weak inhibitions of several parts than by a complete inhibition of a single selected element of that system [3]. Therefore there is an increasing interest in developing drugs that take effect on multiple targets simultaneously but is concurrently a great challenge for medicinal chemists. There has to be a sufficient activity on each target as well as an adequate pharmacokinetic profile [4]. Early design strategies tried to link the pharmacophors of known inhibitors, however these methods often lead to high molecular weight and low ligand efficacy. We present a new rational approach based on a retrosynthetic combinatorial analysis procedure [5] on approved ligands of multiple targets. These RECAP fragments are used to design a large combinatorial library containing molecules featuring chemical properties of each ligand class. The molecules are further validated by machine learning models, like random forests and self-organizing maps, regarding their activity on the targets of interest

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

Photography, Politics and Childhood: Exploring children’s multimodal relations with the public sphere

In qualitative research with children visually oriented and multimodal approaches are identified in the literature as more appropriate for approaching children’s meanings and feelings often deemed to lie beyond the realm of language. In our own research, a comparative ethnography which enquired into the relationships between childhood and public life, with six-to-eight year olds in three cities (Athens, Hyderabad and London), we have reflexively experimented with the employment and remixing of methodologies which would allow us to explore such relationships. In the process of our research, incorporating different visual and ethnographic methods, we have developed a data collection and production process, an adaptation of the photo-story, which allows for a multimodal, processual and reflective enquiry into children’s relationships of concern and politics of care. We review the central visual methods in research with children, we then proceed to provide a documentation of the method, its development and its rationale. Consequently, we provide some examples of the photostory method’s implementation in the Connectors Study together with a discussion of the production processes of the photo-stories themselves and our readings of them. We conclude with a section with reflections on the method, which, we argue provides a departure point from which we may rethink the political in childhood, as well as the ways in which photography is employed as a research method in the social sciences

On the Matter of Time

Drawing on several disciplinary areas, this article considers diverse cultural concepts of time, space, and materiality. It explores historical shifts in ideas about time, observing that these have gone full circle, from visions in which time and space were conflated, through increasingly divergent linear understandings of the relationship between them, to their reunion in contemporary notions of space-time. Making use of long-term ethnographic research and explorations of the topic of Time at Durham University’s Institute of Advanced Study (2012–13), the article considers Aboriginal Australian ideas about relationality and the movement of matter through space and time. It asks why these earliest explanations of the cosmos, though couched in a wholly different idiom, seem to have more in common with the theories proposed by contemporary physicists than with the ideas that dominated the period between the Holocene and the Anthropocene. The analysis suggests that such unexpected resonance between these oldest and newest ideas about time and space may spring from the fact that they share an intense observational focus on material events. Comparing these vastly different but intriguingly compatible worldviews meets interdisciplinary aims in providing a fresh perspective on both of them

Using Multiple Microenvironments to Find Similar Ligand-Binding Sites: Application to Kinase Inhibitor Binding

The recognition of cryptic small-molecular binding sites in protein structures is important for understanding off-target side effects and for recognizing potential new indications for existing drugs. Current methods focus on the geometry and detailed chemical interactions within putative binding pockets, but may not recognize distant similarities where dynamics or modified interactions allow one ligand to bind apparently divergent binding pockets. In this paper, we introduce an algorithm that seeks similar microenvironments within two binding sites, and assesses overall binding site similarity by the presence of multiple shared microenvironments. The method has relatively weak geometric requirements (to allow for conformational change or dynamics in both the ligand and the pocket) and uses multiple biophysical and biochemical measures to characterize the microenvironments (to allow for diverse modes of ligand binding). We term the algorithm PocketFEATURE, since it focuses on pockets using the FEATURE system for characterizing microenvironments. We validate PocketFEATURE first by showing that it can better discriminate sites that bind similar ligands from those that do not, and by showing that we can recognize FAD-binding sites on a proteome scale with Area Under the Curve (AUC) of 92%. We then apply PocketFEATURE to evolutionarily distant kinases, for which the method recognizes several proven distant relationships, and predicts unexpected shared ligand binding. Using experimental data from ChEMBL and Ambit, we show that at high significance level, 40 kinase pairs are predicted to share ligands. Some of these pairs offer new opportunities for inhibiting two proteins in a single pathway

A global view of drug-therapy interactions

Network science is already making an impact on the study of complex systems and offers a promising variety of tools to understand their formation and evolution (1-4) in many disparate fields from large communication networks (5,6), transportation infrastructures (7) and social communities (8,9) to biological systems (1,10,11). Even though new highthroughput technologies have rapidly been generating large amounts of genomic data, drug design has not followed the same development, and it is still complicated and expensive to develop new single-target drugs. Nevertheless, recent approaches suggest that multi-target drug design combined with a network-dependent approach and large-scale systems-oriented strategies (12-14) create a promising framework to combat complex multigenetic disorders like cancer or diabetes. Here, we investigate the human network corresponding to the interactions between all US approved drugs and human therapies, defined by known drug-therapy relationships. Our results show that the key paths in this network are shorter than three steps, indicating that distant therapies are separated by a surprisingly low number of chemical compounds. We also identify a sub-network composed by drugs with high centrality measures (15), which represent the structural back-bone of the drug-therapy system and act as hubs routing information between distant parts of the network. These findings provide for the first time a global map of the largescale organization of all known drugs and associated therapies, bringing new insights on possible strategies for future drug development. Special attention should be given to drugs which combine the two properties of (a) having a high centrality value and (b) acting on multiple targets.Comment: 16 pages, 4 figures. It was submitted to peer review on August 15, 200

Ethnoontology: Ways of world‐building across cultures

This article outlines a program of ethnoontology that brings together empirical research in the ethnosciences with ontological debates in philosophy. First, we survey empirical evidence from heterogeneous cultural contexts and disciplines. Second, we propose a model of cross‐cultural relations between ontologies beyond a simple divide between universalist and relativist models. Third, we argue for an integrative model of ontology building that synthesizes insights from different fields such as biological taxonomy, cognitive science, cultural anthropology, and political ecology. We conclude by arguing that a program of ethnoontology provides philosophers both with insights about traditional issues such as debates about natural kinds and with novel strategies for connecting philosophy with pressing global issues such as the conservation of local environments and the self‐determination of Indigenous communities

Sensory ways to indigenous multimodal literacies : Hands and feet tell the story

This chapter reports original research that asks the question: What are the ways of knowing, being, and communicating that are valued and practiced in Indigenous communities? Literacy curricula, internationally and nationally, typically do not take into account the multi-sensorial dimensions of non-Western forms of representation that go beyond narrow conceptions of print. For example, literacies are often conceived as drawing on print, visual, spatial, gestural, and audio modes, but the role of haptics and locomotion has typically received little attention. This chapter highlights examples of the multi-sensoriality of Indigenous literacies observed in participatory community research with an Indigenous school. It extends recent theories of sensory studies in the history and cultural anthropology of the senses, applying these principles to literacy education. Sensory literacies is a theoretical perspective that gives priority to the sensorial dimensions of the body and its role in communication in literacy practice, because without a sensing body, we cannot know about or communicate with the world. The data demonstrates how the forgotten role of the hands and feet in dominant theories of communication is central to Indigenous identity and literacies. Written by a white academic with an Indigenous researcher, the chapter problematises the privileging of narrow, logocentric, and Western forms of literacy and its implications for rethinking the role of the whole body in literacy and the literacy curriculum for Indigenous students

Biopolitics meets Terrapolitics: Political Ontologies and Governance in Settler-Colonial Australia

Crises persist in Australian Indigenous affairs because current policy approaches do not address the intersection of Indigenous and European political worlds. This paper responds to this challenge by providing a heuristic device for delineating Settler and Indigenous Australian political ontologies and considering their interaction. It first evokes Settler and Aboriginal ontologies as respectively biopolitical (focused through life) and terrapolitical (focused through land). These ideal types help to identify important differences that inform current governance challenges. The paper discusses the entwinement of these traditions as a story of biopolitical dominance wherein Aboriginal people are governed as an “included-exclusion” within the Australian political community. Despite the overall pattern of dominance, this same entwinement offers possibilities for exchange between biopolitics and terrapolitics, and hence for breaking the recurrent crises of Indigenous affairs