Recent advances in antidiabetic drug therapies targeting the enteroinsular axis

The enteroinsular axis (EIA) constitutes a physiological signalling system whereby intestinal endocrine cells secrete incretin hormones following feeding that potentiate insulin secretion and contribute to the regulation of blood glucose homeostasis. The two key hormones responsible are named glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Recent years have witnessed sustained development of antidiabetic therapies that exploit the EIA. Current clinical compounds divide neatly into two classes. One concerns analogues or mimetics of GLP-1, such as exenatide (Byetta) or liraglutide (NN2211). The other group comprises the gliptins (e.g. sitagliptin and vildagliptin) which boost endogenous incretin activity by inhibiting the enzyme dipeptidyl peptidase 4 (DPP 4) that degrades both GLP-1 and GIP. Ongoing research indicates that further incretin and gliptin compounds will become available for clinical use in the near future, offering comparable or improved efficacy. For incretin analogues there is the prospect of prolonged duration of action and alternative routes of administration. This review focuses on recent advances in pre-clinical research and their translation into clinical studies to provide future therapies for type 2 diabetes targeting the EIA. © 2009 Bentham Science Publishers Ltd.

Knowledge-based system for casting process selection

Design of casting entails the knowledge of various interacting factors that are unique to casting process, and, quite often, product designers do not have the required foundry-specific knowledge. Casting designers normally have to liaise with casting experts in order to ensure the product designed is castable and the optimum casting method is selected. This two-way communication results in long design lead times, and lack of it can easily lead to incorrect casting design. A computer-based system at the discretion of a design engineer can, however, alleviate this problem and enhance the prospect of casting design for manufacture. This paper proposes a knowledge-based expert system approach to assist casting product designers in selecting the most suitable casting process for specified casting design requirements, during the design phase of product manufacture. A prototype expert system has been developed, based on production rules knowledge representation technique. The proposed system consists of a number of autonomous but interconnected levels, each dealing with a specific group of factors, namely, casting alloy, shape and complexity parameters, accuracy requirements and comparative costs, based on production quantity. The user interface has been so designed to allow the user to have a clear view of how casting design parameters affect the selection of various casting processes at each level; if necessary, the appropriate design changes can be made to facilitate the castability of the product being designed, or to suit the design to a preferred casting method.

New insights in the moderating effect of switching costs on the satisfaction-repurchase behavior link

Existing studies on the role of switching costs (SC) as moderator of the relationship between satisfaction and repurchase behavior are inconclusive. We attempt to explain these inconclusive findings by synthesizing an amplifying and a lock-in effect, and hypothesize a nonlinear moderating effect. In Study 1 (a main study and three replications), we find strong evidence for an inverted u-shaped moderating effect of overall SC. Our results suggest that satisfaction is a particularly important predictor of repurchase behavior in situations characterized by medium-levels of SC. Based on Prospect Theory, Study 2 (a main study and one replication) reveals that this inverted u-shaped moderating effect of SC is stronger for positive (relational and financial) SC than for negative (procedural) SC. We conclude with recommendations for satisfaction management of different customer segments, and describe possibilities to influence customer switching costs in various industries. © 2014 New York University.

Developing accurate models of the human airways

Objectives Particle delivery to the airways is an attractive prospect for many potential therapeutics, including vaccines. Developing strategies for inhalation of particles provides a targeted, controlled and non-invasive delivery route but, as with all novel therapeutics, in vitro and in vivo testing are needed prior to clinical use. Whilst advanced vaccine testing demands the use of animal models to address safety issues, the production of robust in vitro cellular models would take account of the ethical framework known as the 3Rs (Replacement, Reduction and Refinement of animal use), by permitting initial screening of potential candidates prior to animal use. There is thus a need for relevant, realistic in vitro models of the human airways. Key findings Our laboratory has designed and characterised a multi-cellular model of human airways that takes account of the conditions in the airways and recapitulates many salient features, including the epithelial barrier and mucus secretion. Summary Our human pulmonary models recreate many of the obstacles to successful pulmonary delivery of particles and therefore represent a valid test platform for screening compounds and delivery systems.

Corporate environmental responsibility and accountability:what chance in vulnerable Bangladesh?

Bangladesh has recently been enjoying significant economic growth mainly arising from an export led development strategy. However, in that process its natural environment has been degraded and become more vulnerable in geophysical terms (e.g. environmental pollution). Much of the Bangladeshi population are also vulnerable in socio-economic terms due primarily to widespread poverty. In this context we ask, albeit sceptically, whether there is any chance of holding corporations to account for their environmental responsibilities. Using the notions of vulnerability and ecological rifts we answer this question by providing evidence from published sources and a series of 32 semi-structured interviews with Bangladeshi stakeholder groups. Key findings include, inter alia, corporate reluctance to take responsibility for the environmental impact of their activities. Our interviewees discuss the possibility of a role for mandatory corporate reporting in enhancing corporate accountability and we argue that this is essential if the contradictions and irrationalities of the globalized capitalist system are to be made visible. Achieving such accountability, however, will not be easy due to a lack of political will and the prohibitive costs involved. Incurring such costs could raise the dangerous prospect of Bangladesh losing business to other, less regulated, economies.

Editorial overview:new protein production tools for structural biology

Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.

"And a child shall lead them?": Slavery, childhood, and African cultural identity in Jamaica, 1750--1838

Based primarily on archival evidence collected in Jamaica, this dissertation examined the nature of childhood in the plantation complex between 1750 and 1838, how colonial society and the slave community defined childhood, and how that definition changed over time. It proves how childhood and slavery influenced and changed each other during these years, with the abolitionist movement standing as the main catalyst for change. Although this project chronologically examined the changing nature of slave childhood in Jamaica through four shifts of Jamaican history, each chapter topically focused on slave childhood through the lenses of labor, family, resistance, race, status, culture, education, and freedom. ^ The research showed that although slavery forced slave children into an early adulthood, childhood was a contested process that changed with each generation of children. As the abolitionist movement motivated changes in planter opinion on the value of children to the plantation economy, planters placed increased responsibility on slave children to lead them towards economic stability and profitability. Meanwhile, slave children struggled to survive slavery by reinventing and modifying their ideas of family and kinship and reacting to their situation through various acts of resistance. Although slave parents gained many opportunities to raise their children on their own terms, they struggled to maintain control over that process as planters attempted to change the nature of African cultural identity in Jamaica by impressing Christian and English values on slave children. Under apprenticeship, childhood returned to its previous status as a liability in the eyes of the Jamaican planters. Yet, Jamaican children faced the prospect of an unwritten childhood, one that was free from planter control and gave Jamaican laborers hope for the future. In the end, this dissertation told the story of an overlooked childhood, one that was often defined by Jamaican planters, but frequently contested by the slaves themselves. ^

The use of computing technology in highway construction contractor companies as a Total Jobsite Management Tool (TJMT)

The integration of automation (specifically Global Positioning Systems (GPS)) and Information and Communications Technology (ICT) through the creation of a Total Jobsite Management Tool (TJMT) in construction contractor companies can revolutionize the way contractors do business. The key to this integration is the collection and processing of real-time GPS data that is produced on the jobsite for use in project management applications. This research study established the need for an effective planning and implementation framework to assist construction contractor companies in navigating the terrain of GPS and ICT use. An Implementation Framework was developed using the Action Research approach. The framework consists of three components, as follows: (i) ICT Infrastructure Model, (ii) Organizational Restructuring Model, and (iii) Cost/Benefit Analysis. The conceptual ICT infrastructure model was developed for the purpose of showing decision makers within highway construction companies how to collect, process, and use GPS data for project management applications. The organizational restructuring model was developed to assist companies in the analysis and redesign of business processes, data flows, core job responsibilities, and their organizational structure in order to obtain the maximum benefit at the least cost in implementing GPS as a TJMT. A cost-benefit analysis which identifies and quantifies the cost and benefits (both direct and indirect) was performed in the study to clearly demonstrate the advantages of using GPS as a TJMT. Finally, the study revealed that in order to successfully implement a program to utilize GPS data as a TJMT, it is important for construction companies to understand the various implementation and transitioning issues that arise when implementing this new technology and business strategy. In the study, Factors for Success were identified and ranked to allow a construction company to understand the factors that may contribute to or detract from the prospect for success during implementation. The Implementation Framework developed as a result of this study will serve to guide highway construction companies in the successful integration of GPS and ICT technologies for use as a TJMT.

European integration and democratic consolidation: Spain, Poland and Turkey in comparative perspective

The study explored when, under what conditions, and to what extent did European integration, particularly the European Union’s requirement for democratic conditionality, contribute to democratic consolidation in Spain, Poland, and Turkey? On the basis of a four-part definition, the dissertation examined the democratizing impact of European integration process on each of the following four components of consolidation: (i) holding of fair, free and competitive elections, (ii) protection of fundamental rights, including human and minority rights, (iii) high prospects of regime survival and civilian control of the military, and (iv) legitimacy, elite consensus, and stateness. To assess the relative significance of EU’s democratizing leverage, the thesis also examined domestic and non-EU international dynamics of democratic consolidation in the three countries. By employing two qualitative methods (case study and process-tracing), the study focused on three specific time frames: 1977–1986 for Spain, 1994–2004 for Poland, and 1999–present for Turkey. In addition to official documents, newspapers, and secondary sources, face-to-face interviews made with politicians, academics, experts, bureaucrats, and journalists in the three countries were utilized. The thesis generated several conclusions. First of all, the EU’s democratizing impact is not uniform across different components of democratic consolidation. Moreover, the EU’s democratizing leverage in Spain, Poland, and Turkey involved variations over time for three major reasons: (i) the changing nature of EU’s democratic conditionality over time (ii) varying levels of the EU’s credible commitment to the candidate country’s prospect for membership, and (iii) domestic dynamics in the candidate countries. Furthermore, the European integration process favors democratic consolidation but its magnitude is shaped by the candidate country’s prospect for EU membership and domestic factors in the candidate country. Finally, the study involves a major policy implication for the European Union: unless the EU provides a clear prospect for membership, its democratizing leverage will be limited in the candidate countries.

Smoke on the water: the interplay of fire and water flow on Everglades restoration

Recent research makes clear that much of the Everglade’s flora and fauna have evolved to tolerate or require frequent fires. Nevertheless, restoration of the Everglades has thus far been conceptualized as primarily a water reallocation project. These two forces are directly linked by the influence of water flows on fire fuel moisture content, and are indirectly linked through a series of complex feedback loops. This interaction is made more complex by the alteration and compartmentalization of current water flows and fire regimes, the lack of communication between water and fire management agencies, and the already imperiled state of many local species. It is unlikely, therefore, that restoring water flows will automatically restore the appropriate fire regimes, leaving the prospect of successful restoration in some doubt. The decline of the Cape Sable seaside sparrow, and its potential for recovery, illustrates the complexity of the situation.

Online Pricing Practice for Hotel Room Rates in China: The Case of Shanghai

Travel websites that enable hotel room reservations have created unprecedented business opportunities. However, they have also overloaded hotel customers with information. This situation is particularly true of China, an emerging country with the largest population in the world and the most promising growth prospect in tourism. This study investigated the room-rate pricing practice of five online distribution channels, measured by the lowest available rates. These online channels priced hotels of different categories in Shanghai, China’s largest city. Empirical findings indicated that local websites offered lower room rates than international websites for the selected hotels in different categories. Specifically, Chinatravel consistently offered the lowest room rates for the selected hotels.

Acompanhamento coletivo do crescimento e desenvolvimento infantil: participação de mães/cuidadores

This study aimed to analyze the participation of mothers/caregivers from the perspective of the health care model that directs the collective monitoring of child growth and development. This is an exploratory and descriptive research with qualitative approach, carried out in two Family Health Units located in the city of Natal/RN. Data were collected between August and September 2014, through participant observation and semi-structured interview technique, with mothers of infants seen at follow-up visits collective child growth and development. A total of 13 mothers were included who met the following inclusion criteria: being a mother/caregiver responsible for the care of children who have attended one or more meeting of collective monitoring of child growth and development. Exclusion criteria was established: users outside the area covered by the Health Unit Family and who did not use the National Health System as the primary health care service. For the treatment of the collected material, the content analysis was used, thematic Bardin. The study followed the ethical and legal principles governing the scientific research on human subjects recommended by Resolution nº. 466/2012 of the National Health Council and its realization occurred with the approval of the project in the Research Ethics Committee of the Federal University of Rio Grande do North, which was approved by Opinion Embodied nº. 719 949, of June 27, 2014, and Certificate Presentation of Findings Ethics No 32510514.7.0000.5537. Although not conceptualize theoretically mothers demonstrated that collective consultations of child growth and development are actions aimed at health surveillance model, since most pointed monitoring your child to actions that can be measured. Even with that, it was established the existence of health promotion actions by reporting the exchange of experience and leadership of the subjects in collective action, factor facilitated by the link established between users and professionals and users. In this action there is the induction of permanent horizontal relationship where we seek to combine popular knowledge to scientific knowledge in order to promote the integral care for the child. However, it is still possible to find professionals who directs its assistance only to pathological processes and fail to create comprehensive care alternatives. In addition, there is still embezzlement in multi that should provide care to the child population. This factor may be related to their professional training, and thus an issue that can last for a few years. We conclude that it is necessary to incorporate alternatives and models of care that support overcoming limitations and enhancing the health of the population, involving it in the prospect of a better quality of life and therefore health.

Entre elas: políticas públicas e cidadania de travestis e mulheres transexuais de uma ONG em Natal/RN

The core of this research it is anchored in the analysis of the relationship between experiences and experiences of transvestite and transsexual women and citizenship category in Natal. For this, we analyzed, at first, the unfolding instilled in acting from the agenda of a Non Governmental Organization of the city, the Atransparência. In a second, and more importantly, time, reflections of those actions were followed in the daily and transgender women in the city belonging to NGOs. Methodologically, work is characterized as a qualitative research, with ethnographic deployment, made possible through interviews with semi-structured questionnaires. The analysis of the collected material was possible from the discourse analysis (Foucault, 1996), as well as qualitative analysis (Caregnato and Mutti, 2006). Theoretically, it was done the exercise to think queer theory conciliated her with the prospect of criticism of eucorêntrismo of power and knowledge, with fundamental emphasis on the relationship between theoretical national queers - Bento (2014), Miscolci (2014), Pelúcio (2014 ) and Pereira (2012) - authors and descolonial such as Mignolo (2008) Quijano (2005).

Articulação entre saúde mental infanto-juvenil e atenção básica em Natal-RN: limites e possibilidades

In the case of Brazilian Psychiatric Reformation, mental health juvenile reveals itself as a great challenge, with major gaps in terms of needs, services and actions on mental illness in children and adolescents. This research is a qualitative study of descriptive and exploratory, having to analyze the actions and practices of mental health juvenile articulated between the Psychosocial Care Center juvenile (Caps i) and the basic care in Natal-RN, and specific, identify the limits and possibilities for an important precedent of the care network. After submission to the Research Ethics Committee (CEP) of the University Hospital Onofre Lopes (HUOL) of the Federal University of Rio Grande do Norte (UFRN) obtained approval contained in opinion number 777.067 / 2014. For the data collection, it was initially carried out a documentary research in the Municipal Health Department of Christmas about the phenomenon under study, and subsequently, applied semi-structured interviews with the subjects of the research, which were workers Caps i of Natal-RN. The analysis was woven as the thematic analysis technique, understood within the method of content analysis. The results and discussions were organized by categories and subcategories, namely: CATEGORY 1: Limits and weaknesses in the linkage between the Caps i and basic care, with the subcategories: 1.1 Lack of specialized services and devices articulators in network, 1.2 The diversity of situations in the demand juvenile assisted; CATEGORY 2: possibilities for an effective network, with the subcategory: 2.1 Intersectoral collaboration as a strategy for solving attention. The analysis revealed that the integration and coordination of mental health services juvenile and primary care in the city of Natal-RN, has incipient initiatives and/or inadequate for the resolvability intersectoral, where the devices of attention to health involved cannot establish bonds effective and long-lasting in the perspective of co-responsibility and sharing of care. On the other hand, it appears that the existing shares and practiced, configure an exercise in approximation to the dialog between mental health juvenile and basic care. It is highlighted that the shared care and the establishment of intersectoral collaboration within and outside of the health sector is possibility of facilitating the necessary dialog between the services and professionals involved, thus, enabling a better prospect of resolvability of the Network of Psychosocial Care for the youth in reality being investigated.

Derivation of base-line geochemistry, petrography, and isotopic data for the host rocks to the Lucky Strike deposit and comparison with data from other alteration zones, Buchans Mining Camp, Newfoundland

The Buchans ore bodies of central Newfoundland represent some of the highest grade VMS deposits ever mined. These Kuroko-type deposits are also known for the well developed and preserved nature of the mechanically transported deposits. The deposits are hosted in Cambro-Ordovician, dominantly calc-alkaline, bimodal volcanic and epiclastic sequences of the Notre Dame Subzone, Newfoundland Appalachians. Stratigraphic relationships in this zone are complicated by extensively developed, brittledominated Silurian thrust faulting. Hydrothermal alteration of host rocks is a common feature of nearly all VMS deposits, and the recognition of these zones has been a key exploration tool. Alteration of host rocks has long been described to be spatially associated with the Buchans ore bodies, most notably with the larger in-situ deposits. This report represents a base-line study in which a complete documentation of the geochemical variance, in terms of both primary (igneous) and alteration effects, is presented from altered volcanic rocks in the vicinity of the Lucky Strike deposit (LSZ), the largest in-situ deposit in the Buchans camp. Packages of altered rocks also occur away from the immediate mining areas and constitute new targets for exploration. These zones, identified mostly by recent and previous drilling, represent untested targets and include the Powerhouse (PHZ), Woodmans Brook (WBZ) and Airport (APZ) alteration zones, as well as the Middle Branch alteration zone (MBZ), which represents a more distal alteration facies related to Buchans ore-formation. Data from each of these zones were compared to those from the LSZ in order to evaluate their relative propectivity. Derived litho geochemical data served two functions: (i) to define primary (igneous) trends and (ii) secondary alteration trends. Primary trends were established using immobile, or conservative, elements (i. e., HFSE, REE, Th, Ti0₂, Al₂0₃, P₂0₅). From these, altered volcanic rocks were interpreted in terms of composition (e.g., basalt - rhyodacite) and magmatic affinity (e.g., calc-alkaline vs. tholeiitic). The information suggests that bimodality is a common feature of all zones, with most rocks plotting as either basalt/andesite or dacite (or rhyodacite); andesitic senso stricto compositions are rare. Magmatic affinities are more varied and complex, but indicate that all units are arc volcanic sequences. Rocks from the LSZ/MBZ represent a transitional to calc-alkalic sequence, however, a slight shift in key geochemical discriminants occurs between the foot-wall to the hanging-wall. Specifically, mafic and felsic lavas of the foot-wall are of transitional (or mildly calc-alkaline) affinity whereas the hanging-wall rocks are relatively more strongly calc-alkaline as indicated by enriched LREE/HREE and higher ZrN, NbN and other ratios in the latter. The geochemical variations also serve as a means to separate the units (at least the felsic rocks) into hanging-wall and foot-wall sequences, therefore providing a valuable exploration tool. Volcanic rocks from the WBZ/PHZ (and probably the APZ) are more typical of tholeiitic to transitional suites, yielding flatter mantlenormalized REE patterns and lower ZrN ratios. Thus, the relationships between the immediate mining area (represented by LSZ/MBZ) and the Buchans East (PHZ/WBZ) and the APZ are uncertain. Host rocks for all zones consist of mafic to felsic volcanic rocks, though the proportion of pyroclastic and epiclastic rocks, is greatest at the LSZ. Phenocryst assemblages and textures are common in all zones, with minor exceptions, and are not useful for discrimination purposes. Felsic rocks from all zones are dominated by sericiteclay+/- silica alteration, whereas mafic rocks are dominated by chlorite- quartz- sericite alteration. Pyrite is ubiquitous in all moderately altered rocks and minor associated base metal sulphides occur locally. The exception is at Lucky Strike, where stockwork quartzveining contains abundant base-metal mineralization and barite. Rocks completely comprised of chlorite (chloritite) also occur in the LSZ foot-wall. In addition, K-feldspar alteration occurs in felsic volcanic rocks at the MBZ associated with Zn-Pb-Ba and, notably, without chlorite. This zone represents a peripheral, but proximal, zone of alteration induced by lower temperature hydrothermal fluids, presumably with little influence from seawater. Alteration geochemistry was interpreted from raw data as well as from mass balanced (recalculated) data derived from immobile element pairs. The data from the LSZ/MBZ indicate a range in the degree of alteration from only minor to severe modification of precursor compositions. Ba tends to show a strong positive correlation with K₂0, although most Ba occurs as barite. With respect to mass changes, Al₂0₃, Ti0₂ and P₂0₅ were shown to be immobile. Nearly all rocks display mass loss of Na₂O, CaO, and Sr reflecting feldspar destruction. These trends are usually mirrored by K₂0-Rb and MgO addition, indicating sericitic and chloritic alteration, respectively. More substantial gains ofK₂0 often occur in rocks with K-feldspar alteration, whereas a few samples also displayed excessive MgO enrichment and represent chloritites. Fe₂0₃ indicates both chlorite and sulphide formation. Si0₂ addition is almost always the case for the altered mafic rocks as silica often infills amygdules and replaces the finer tuffaceous material. The felsic rocks display more variability in Si0₂. Silicic, sericitic and chloritic alteration trends were observed from the other zones, but not K-feldspar, chloritite, or barite. Microprobe analysis of chlorites, sericites and carbonates indicate: (i) sericites from all zones are defined as muscovite and are not phengitic; (ii) at the LSZ, chlorites ranged from Fe-Mg chlorites (pycnochlorite) to Mg-rich chlorite (penninite), with the latter occurring in the stockwork zone and more proximal alteration facies; (iii) chlorites from the WBZ were typical of those from the more distal alteration facies of the LSZ, plotting as ripidolite to pycnochlorite; (iv) conversely, chlorite from the PHZ plot with Mg-Al-rich compositions (chlinochlore to penninite); and (v) carbonate species from each zone are also varied, with calcite occurring in each zone, in addition to dolomite and ankerite in the PHZ and WBZ, respectively. Lead isotope ratios for galena separates from the different various zones, when combined with data from older studies, tend to cluster into four distinctive fields. Overall, the data plot on a broad mixing line and indicate evolution in a relatively low-μ environment. Data from sulphide stringers in altered MBZ rocks, as well as from clastic sulphides (Sandfill prospect), plot in the Buchans ore field, as do the data for galena from altered rocks in the APZ. Samples from the Buchans East area are even more primitive than the Buchans ores, with lead from the PHZ plotting with the Connel Option prospect and data from the WBZ matching that of the Skidder prospect. A sample from a newly discovered debris flow-type sulphide occurrence (Middle Branch East) yields lead isotope ratios that are slightly more radiogenic than Buchans and plot with the Mary March alteration zone. Data within each cluster are interpreted to represent derivation from individual hydrothermal systems in which metals were derived from a common source.