Investigating the use of Mechanochemistry to Improve the Sustainability of Chemical Synthesis and Drug Discovery

Presented herein is an exploration into mechanochemical techniques for organic synthesis. Mechanochemistry is an exciting tool where mechanical energy is used to enable reactivity via the impact of balls within a jar. It has recently gained increased interest due to the unique solvent free reaction set-up. Currently, from a sustainability perspective, organic synthesis can be an incredibly wasteful endeavour that must be improved to ensure more sustainable working practices. In this report, three distinctive areas have been targeted to either uncover a new process or improve on reactions that are frequently used in the chemical industry

The Molecular Basis For Rapid Ca2+ Transport Across The Inner Mitochondrial Membrane

Ca2+ uptake by energized mitochondria regulates bioenergetics, apoptosis, and global Ca2+ signaling. Ca2+ entry into mitochondria is mediated by the Ca2+ uniporter-channel complex containing MCU, the Ca2+-selective pore, and associated regulatory proteins. The precise roles of these regulatory proteins and their relative stoichiometry in the complex have yet to be elucidated. MICU1 was proposed to be necessary for MCU activity whereas subsequent studies suggested a role for MICU1 and its paralog MICU2 in channel inhibition in the low-cytoplasmic Ca2+ ([Ca2+]c) regime, a mechanism referred to as “gatekeeping”. EMRE is required for MCU channel function and coupling of MICU1/2-mediated gatekeeping, but its stoichiometry relative to MCU in the native complex is unclear. We measured MCU activity over a wide range of quantitatively controlled and recorded [Ca2+]c to identify the regulatory function of the MICU1 and 2 and introduced mutations into Ca2+-binding sites in each protein to determine the mechanism by which [Ca2+]c controls channel activity. We then addressed the functional consequences of manipulating the relative stoichiometry of EMRE and MCU by introducing tagged MCU and EMRE in MCU/EMRE double-knockout cells to directly compare their expression and created a series of MCU-EMRE concatemers with multiple concatenated MCU subunits fused to EMRE, allowing us to “fix” their stoichiometry. MICU1 alone can mediate gatekeeping as well as highly cooperative activation of MCU activity, whereas the fundamental role of MICU2 is to regulate the threshold and gain of MICU1-mediated inhibition and activation of MCU. Our results provide a unifying model for the roles of the MICU1/2 heterodimer in MCU-channel regulation and suggest an evolutionary role for MICU2 in spatially restricting Ca2+ uptake to mitochondria localized to nanodomains of high (\u3e2 μM) [Ca2+]c. Furthermore, while incorporation of a single EMRE reconstitutes channel activity, additional EMRE subunits increase the [Ca2+]c-threshold required for relief of gatekeeping. Endogenous channels most likely contain two EMRE subunits which tether two MICU1/2-dimers to the complex. These findings have important implications for developing new therapies to target diseases arising from dysregulation of mitochondrial Ca2+-transport

Preserving Large Farming Landscapes: The Case of Lancaster County, Pennsylvania

Preserving large farming landscapes is one of the main goals of farmland preservation programs. Other goals include protecting highly productive soils, maintaining and enhancing the local farming economy, and promoting locally produced fresh food. Farmland preservation programs take time, however, because of the hefty funding requirements and the detailed process of preserving farmland through the acquisition of conservation easements by purchase or donation. The standard measures of dollars spent and farmland acres preserved do not give an accurate picture of the spatial outcomes of preservation and preservation effectiveness. Three other measures better reflect the spatial effectiveness of farmland preservation: acreage and percentage of preserved farm parcels located in agricultural zones, number and acreage of preserved farm parcels in large contiguous blocks, and number and acreage of preserved farm parcels along growth boundaries. Scattered preserved farms and preserved farms not located in agricultural zones are likely to face more nonfarm development nearby as well as problems with non- farm neighbors. The farmland preservation effort in Lancaster County, Pennsylvania, provides an important case study of the pattern of farmland preservation over time. Other counties and land trusts can employ geographic information systems (GIS) methods in this study to monitor and evalu- ate the progress of their farmland preservation efforts

Lead acid battery recycling for the twenty-first century

There is a growing need to develop novel processes to recover lead from end-of-life lead-acid batteries, due to increasing energy costs of pyrometallurgical lead recovery, the resulting CO2 emissions and the catastrophic health implications of lead exposure from lead-to-air emissions. To address these issues, we are developing an iono-metallurgical process, aiming to displace the pyrometallurgical process that has dominated lead production for millennia. The proposed process involves the dissolution of Pb salts into the deep eutectic solvent (DES) Ethaline 200, a liquid formed when a 1 : 2 molar ratio of choline chloride and ethylene glycol are mixed together. Once dissolved, the Pb can be recovered through electrodeposition and the liquid can then be recycled for further Pb recycling. Firstly, DESs are being used to dissolve the lead compounds (PbCO3, PbO, PbO2 and PbSO4) involved and their solubilities measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The resulting Pb2+ species are then reduced and electrodeposited as elemental lead at the cathode of an electrochemical cell; cyclic voltammetry and chronoamperometry are being used to determine the electrodeposition behaviour and mechanism. The electrodeposited films were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). We discuss the implications and opportunities of such processes

Distributing Coalition Value Calculations to Coalition Members

Within characteristic function games, agents have the option of joining one of many different coalitions, based on the utility value of each candidate coalition. However, determining this utility value can be computationally complex since the number of coalitions increases exponentially with the number of agents available. Various approaches have been proposed that mediate this problem by distributing the computational load so that each agent calculates only a subset of coalition values. However, current approaches are either highly inefficient due to redundant calculations, or make the benevolence assumption (i.e. are not suitable for adversarial environments). We introduce DCG, a novel algorithm that distributes the calculations of coalition utility values across a community of agents, such that: (i) no inter-agent communication is required; (ii) the coalition value calculations are (approximately) equally partitioned into shares, one for each agent; (iii) the utility value is calculated only once for each coalition, thus redundant calculations are eliminated; (iv) there is an equal number of operations for agents with equal sized shares; and (v) an agent is only allocated those coalitions in which it is a potential member. The DCG algorithm is pre- sented and illustrated by means of an example. We formally prove that our approach allocates all of the coalitions to the agents, and that each coalition is assigned once and only once

Managing end of life medications at home--accounts of bereaved family carers: a qualitative interview study.

OBJECTIVE: To explore how bereaved family members recall managing end of life medications when delivering care to a patient dying at home in England. DESIGN: Qualitative study. SETTING: Domestic homes in two contrasting areas in England. PARTICIPANTS: 59 bereaved family carers who have delivered care to a patient who spent a minimum of 2 weeks at home prior to their death from cancer or other non-malignant condition. Cases were excluded if the place of death was: a hospice, nursing home or National Health Service (NHS) hospital. RESULTS: Participants identified a number of important concerns about managing end of life medication for the dying person at home. Although some support with medications is provided by general practitioners and nurses in the community, family carers take primary responsibility for drug administration and storage. They reported anxiety about giving correct and timely dosages, and concerns about keeping the patient comfortable without overdosing them or risking shortening their lives. In particular, they reported that certain analgesic medications, especially opioids, were considered to have a symbolic significance increasing analgesia requirements, and the use of a syringe driver was associated with deterioration and approaching death. Key barriers to managing end of life medications at home included: complex regimes; unwanted responsibility in deciding when to use 'as needed' medication; disagreements with professional staff, and anxiety about medication errors, especially if perceived to have implications for survival. CONCLUSIONS: Family carers require more information about end of life drugs and their effects, support and training in managing medication for a dying person

Frequency of shearing increases growth of fibre and changes objective and subjective attributes of Angora goat fleeces

The impact of genotype and of frequency and timing of shearing, on mohair attributes and production of modern Angora goats was studied. Goats in the southern hemisphere grazed pastures between February 2004 and 2006. There were seven shearing treatments by three genetic strains with four or eight replicates of individual goats. Treatments were: three different 6-month shearing intervals and two of 12-month shearing intervals with different months of shearing, a 7-month winter shearing interval and a 3-month shearing interval. Genetic strain was based on sire line: 1&middot;0 South African; 1&middot;0 Texan; and Mixed 0&middot;5 South African and 0&middot;5 Texan. Annual greasy mohair production was 5&middot;08 kg, and average clean fleece production was 4&middot;37 kg. The Angora goats produced an annual clean fleece equivalent to 0&middot;122 of their mean fleece-free live weight which was equal to 0&middot;34 g/kg/day. Measurements were analysed over the period of spring 2004 shearing to spring 2005 shearing, excluding the June&ndash;December shearing treatment. Increased frequency of shearing increased fleece growth and affected 13 objective and subjective attributes of mohair that were evaluated including clean washing yield, fibre diameter and fibre diameter variation, incidence of medullated fibres, staple length, fibre curvature, crimp frequency, style, staple definition, staple fibre entanglement and staple tip shape. The direction of these effects were generally favourable and for most attributes the magnitude of the response was linear and commercially important. Each additional shearing resulted in an additional 149 g of clean mohair representing 0&middot;034 of the annual clean mohair production. This increase was associated with a 0&middot;6 cm increase in staple length and 0&middot;32 &mu;m increase in mean fibre diameter. In conclusion, Angora goats shorn less frequently grew less mohair that was more likely to be entangled in spring. Managers of Angora goats should take note of these findings.<br /

Digital terrain analysis reveals new insights into the topographic context of Australian Aboriginal stone arrangements

Satellite-derived surface elevation models are an important resource for landscape archaeological studies. Digital elevation data is useful for classifying land features, characterizing terrain morphology, and discriminating the geomorphic context of archaeological phenomena. This paper shows how remotely sensed elevation data obtained from the Japan Aerospace Exploration Agency's Advanced Land Observing Satellite was integrated with local land system spatial data to digitally classify the topographic slope position of seven broad land classes. The motivation of our research was to employ an objective method that would allow researchers to geomorphometrically discriminate the topographic context of Aboriginal stone arrangements, an important archaeological site type in the Pilbara region of northwest Australia. The resulting digital terrain model demonstrates that stone arrangement sites are strongly correlated with upper topographic land features, a finding that contradicts previous site recordings and fundamentally changes our understanding of where stone arrangement sites are likely to have been constructed. The outcome of this research provides investigators with a stronger foundation for testing hypotheses and developing archaeological models. To some degree, our results also hint at the possible functions of stone arrangements, which have largely remained enigmatic to researchers

What fosters or prevents interprofessional teamworking in primary and community care? A literature review

Background: The increase in prevalence of long-term conditions in Western societies, with the subsequent need for non-acute quality patient healthcare, has brought the issue of collaboration between health professionals to the fore. Within primary care, it has been suggested that multidisciplinary teamworking is essential to develop an integrated approach to promoting and maintaining the health of the population whilst improving service effectiveness. Although it is becoming widely accepted that no single discipline can provide complete care for patients with a long-term condition, in practice, interprofessional working is not always achieved. Objectives: This review aimed to explore the factors that inhibit or facilitate interprofessional teamworking in primary and community care settings, in order to inform development of multidisciplinary working at the turn of the century. Design: A comprehensive search of the literature was undertaken using a variety of approaches to identify appropriate literature for inclusion in the study. The selected articles used both qualitative and quantitative research methods. Findings: Following a thematic analysis of the literature, two main themes emerged that had an impact on interprofessional teamworking: team structure and team processes. Within these two themes, six categories were identified: team premises; team size and composition; organisational support; team meetings; clear goals and objectives; and audit. The complex nature of interprofessional teamworking in primary care meant that despite teamwork being an efficient and productive way of achieving goals and results, several barriers exist that hinder its potential from becoming fully exploited; implications and recommendations for practice are discussed. Conclusions: These findings can inform development of current best practice, although further research needs to be conducted into multidisciplinary teamworking at both the team and organisation level, to ensure that enhancement and maintenance of teamwork leads to an improved quality of healthcare provision. © 2007 Elsevier Ltd. All rights reserved