93 resultados para Pre-Mesozoic basement of Iberia


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A surface plasmon resonance-based solution affinity assay is described for measuring the Kd of binding of heparin/heparan sulfate-binding proteins with a variety of ligands. The assay involves the passage of a pre-equilibrated solution of protein and ligand over a sensor chip onto which heparin has been immobilised. Heparin sensor chips prepared by four different methods, including biotin–streptavidin affinity capture and direct covalent attachment to the chip surface, were successfully used in the assay and gave similar Kd values. The assay is applicable to a wide variety of heparin/HS-binding proteins of diverse structure and function (e.g., FGF-1, FGF-2, VEGF, IL-8, MCP-2, ATIII, PF4) and to ligands of varying molecular weight and degree of sulfation (e.g., heparin, PI-88, sucrose octasulfate, naphthalene trisulfonate) and is thus well suited for the rapid screening of ligands in drug discovery applications.

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Heart damage caused by acute myocardial infarction (AMI) is a leading cause of death and disability in Australia. Novel therapies are still required for the treatment of this condition due to the poor reparative ability of the heart. As such, cellular therapies that assist in the recovery of heart muscle are of great current interest. Culture expanded mesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in pre-clinical studies of AMI. For MSC-based therapies in the clinic, an intravenous route of administration would ideally be used due to the low cost, ease of delivery and relative safety. The study of MSC migration is therefore clinically relevant for a minimally invasive cell therapy to promote regeneration of damaged tissue. C57BL/6, UBI-GFP-BL/6 and CD44-/-/GFP+/+ mice were utilised to investigate mMSC migration. To assist in murine models of MSC migration, a novel method was used for the isolation of murine MSC (mMSC). These mMSC were then expanded in culture and putative mMSC were positive for Sca-1, CD90.2, and CD44 and were negative for CD45 and CD11b. Furthermore, mMSC from C57BL/6 and UBI-GFP-BL/6 mice were shown to differentiate into cells of the mesodermal lineage. Cells from CD44-/-/GFP+/+ mice were positive for Sca-1 and CD90.2, and negative for CD44, CD45 and CD11b however, these cells were unable to differentiate into adipocytes and chondrocytes and express lineage specific genes, PLIN and ACAN. Analysis of mMSC chemokine receptor (CR) expression showed that although mMSC do express chemokine receptors, (including those specific for chemokines released after AMI), these were low or undetectable by mRNA. However, protein expression could be detected, which was predominantly cytoplasmic. It was further shown that in both healthy (unperturbed) and inflamed tissues, mMSC had very little specific migration and engraftment after intravenous injection. To determine if poor mMSC migration was due to the inability of mMSC to respond to chemotactic stimuli, chemokine expression in bone marrow, skin injury and hearts (healthy and after AMI) was analysed at various time points by quantitative real-time PCR (qRT PCR). Many chemokines were up-regulated after skin biopsy and AMI, but the highest acute levels were found for CXCL12 and CCL7. Due to their high expression in infarcted hearts, the chemokines CXCL12 and CCL7 were tested for their effect on mMSC migration. Despite CR expression at both protein and mRNA levels, migration in response to CXCL12 and CCL7 was low in mMSC cultured on Nunclon plastic. A novel tissue culture plastic technology (UpCellTM) was then used that allowed gentle non-enzymatic dissociation of mMSC, thus preserving surface expression of the CRs. Despite this the in vitro data indicated that CXCL12 fails to induce significant migration ability of mMSC, while CCL7 induces significant, but low-level migration. We speculated this may be because of low levels of surface expression of chemokine receptors. In a strategy to increase cell surface expression of mMSC chemokine receptors and enhance their in vitro and in vivo migration capacity, mMSC were pre-treated with pro-inflammatory cytokines. Increased levels of both mRNA and surface protein expression were found for CRs by pre-treating mMSC with pro-inflammatory cytokines including TNF-á, IFN-ã, IL-1á and IL-6. Furthermore, the chemotactic response of mMSC to CXCL12 and CCL7 was significantly higher with these pretreated cells. Finally, the effectiveness of this type of cell manipulation was demonstrated in vivo, where mMSC pre-treated with TNF-á and IFN-ã showed significantly increased migration in skin injury and AMI models. Therefore this thesis has demonstrated, using in vitro and in vivo models, the potential for prior manipulation of MSC as a possible means for increasing the utility of intravenously delivery for MSC-based cellular therapies.

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Background There is little scientific evidence to support the usual practice of providing outpatient rehabilitation to patients undergoing total knee replacement surgery (TKR) immediately after discharge from the orthopaedic ward. It is hypothesised that the lack of clinical benefit is due to the low exercise intensity tolerated at this time, with patients still recovering from the effects of major orthopaedic surgery. The aim of the proposed clinical trial is to investigate the clinical and cost effectiveness of a novel rehabilitation strategy, consisting of an initial home exercise programme followed, approximately six weeks later, by higher intensity outpatient exercise classes. Methods/Design In this multicentre randomised controlled trial, 600 patients undergoing primary TKR will be recruited at the orthopaedic pre-admission clinic of 10 large public and private hospitals in Australia. There will be no change to the medical or rehabilitative care usually provided while the participant is admitted to the orthopaedic ward. After TKR, but prior to discharge from the orthopaedic ward, participants will be randomised to either the novel rehabilitation strategy or usual rehabilitative care as provided by the hospital or recommended by the orthopaedic surgeon. Outcomes assessments will be conducted at baseline (pre-admission clinic) and at 6 weeks, 6 months and 12 months following randomisation. The primary outcomes will be self-reported knee pain and physical function. Secondary outcomes include quality of life and objective measures of physical performance. Health economic data (health sector and community service utilisation, loss of productivity) will be recorded prospectively by participants in a patient diary. This patient cohort will also be followed-up annually for five years for knee pain, physical function and the need or actual incidence of further joint replacement surgery. Discussion The results of this pragmatic clinical trial can be directly implemented into clinical practice. If beneficial, the novel rehabilitation strategy of utilising outpatient exercise classes during a later rehabilitation phase would provide a feasible and potentially cost-effective intervention to optimise the physical well-being of the large number of people undergoing TKR.

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In this article we identify how computational automation achieved through programming has enabled a new class of music technologies with generative music capabilities. These generative systems can have a degree of music making autonomy that impacts on our relationships with them; we suggest that this coincides with a shift in the music-equipment relationship from tool use to a partnership. This partnership relationship can occur when we use technologies that display qualities of agency. It raises questions about the kinds of skills and knowledge that are necessary to interact musically in such a partnership. These are qualities of musicianship we call eBility. In this paper we seek to define what eBility might consist of and how consideration of it might effect music education practice. The 'e' in eBility refers not only to the electronic nature of computing systems but also to the ethical, enabling, experiential and educational dimensions of the creative relationship with technologies with agency. We hope to initiate a discussion around differentiating what we term representational technologies from those with agency and begin to uncover the implications of these ideas for music educators in schools and communities. We hope also to elucidate the emergent theory and practice that has enabled the development of strategies for optimising this kind of eBility where the tool becomes partner. The identification of musical technologies with agency adds to the authors’ list of metaphors for technology use in music education that previously included tool, medium and instrument. We illustrate these ideas with examples and with data from our work with the jam2jam interactive music system. In this discussion we will outline our experiences with jam2jam as an example of a technology with agency and describe the aspects of eBility that interaction with it promotes.

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A zero-energy home (ZEH) is a residential dwelling that generates as much energy annually from onsite renewable sources, as it consumes in its operation. A positive energy home (PEH) generates more energy than it consumes. The key design and construction elements, and costs and benefits of such buildings, are the subject of increasing research globally. Approaching this topic from the perspective of the role of such homes in the planning and development ‘supply chain’, this paper presents the measured outcomes of a PEH and discusses urban design implications. Using twelve months of detailed performance data of an occupied sub-tropical home, the paper analyses the design approach and performance outcomes that enable it to be classified as ‘positive energy’. Second, it analyses both the urban design strategies that assisted the house in achieving its positive energy status, and the impacts of such housing on urban design and infrastructure. Third, the triple bottom line implications are discussed from the viewpoint of both the individual household and the broader community. The paper concludes with recommendations for research areas required to further underpin and quantify the role of ZEHs and PEHs in enabling and supporting the economic, social and ecological sustainability of urban developments.

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In this volume we compile and comment on a collection of some of the most important works on nascent entrepreneurship that have appeared in the last two decades. We do not go further back than that because up until1992 hardly any systematic research on the pre-operational stage of business creation was undertaken. In that year, the terms 'nascent entrepreneur' and 'nascent venture' appear for the first time in the research literature (Reynolds and Miller, Chapter l, 1992; Reynolds and White, 1992). This signals the emergence of a new research paradigm designed to study• business creation processes empirically at very early stages, before an operational firm has come into existence. The most central feature of this type of research is that it identifies a statistically representative sample of nascent entrepreneurs (NEs)- people engaged in ongoing but not yet operational business start-ups- via screening interviews with a very large random sample of adults. The overarching research questions pursued in this emerging research tradition are the following: 1. What proportion of individuals (in various population subgroups) are trying to start a new business at any given time? 2. What led them to engage in the creation of a new business? 3. What characteristics and behaviors associated with the founder(s), the venture, the environment and the process are associated with persistence, progress and success in trying to start a new business?

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This project has blended two streams of enquiry: temporary and transportable construction technology, and flexible blended-learning environments. It seeks to develop prototypes for a series of environments suited for the activities of learning (future-proofed schools), as practiced in the twenty first century. The research utilises techniques of: historic survey, case study, first-hand observation, and architectural design (as research). The design comprises three major components: The determinate landscape: in-situ concrete ‘plate’ that is permanent. The indeterminate landscape: a kit of pre-fabricated 2-D panels assembled in a unique manner at each site to suit the client and context; manufactured to the principles of design-for-disassembly. The stations: pre-fabricated packages of highly-serviced space connected through the determinate landscape. This project was submitted to the ‘Future Proofing Schools’ competition (professional category) in October 2011. The competition was part of a research project supported under the Australian Research Council’s Linkage Grant funding scheme (project LP0991146).

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Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.

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An increase in the likelihood of navigational collisions in port waters has put focus on the collision avoidance process in port traffic safety. The most widely used on-board collision avoidance system is the automatic radar plotting aid which is a passive warning system that triggers an alert based on the pilot’s pre-defined indicators of distance and time proximities at the closest point of approaches in encounters with nearby vessels. To better help pilot in decision making in close quarter situations, collision risk should be considered as a continuous monotonic function of the proximities and risk perception should be considered probabilistically. This paper derives an ordered probit regression model to study perceived collision risks. To illustrate the procedure, the risks perceived by Singapore port pilots were obtained to calibrate the regression model. The results demonstrate that a framework based on the probabilistic risk assessment model can be used to give a better understanding of collision risk and to define a more appropriate level of evasive actions.

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Little past empirical support has been found for the efficacy of motorcycle rider training as a road safety countermeasure. However, it has been argued that rider training should focus more particularly on the psychosocial factors that influence risk taking behaviour in addition to the traditional practice of developing vehicle-handling skills. This paper examines how rider training to reduce risk taking could be guided by appropriate theories. Two fundamental perspectives are examined: firstly training can be considered in terms of behaviour change, and secondly in terms of adult learning. Whilst behaviour change theories assume some pre-existing level of dysfunctional behaviour, an adult learning perspective does not necessarily carry this assumption. This distinction in perspectives conceptually aligns with the notions of intervention and prevention (respectively), with possible implications for specific target groups for pre-licence and post-licence training. The application of the Theory of Reasoned Action (Ajzen & Fishbein, 1975, 1980) and Transformative Learning Theory (Mezirow, 1997) to a pre-licence rider training program in Queensland, Australia is discussed.

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Quality oriented management systems and methods have become the dominant business and governance paradigm. From this perspective, satisfying customers’ expectations by supplying reliable, good quality products and services is the key factor for an organization and even government. During recent decades, Statistical Quality Control (SQC) methods have been developed as the technical core of quality management and continuous improvement philosophy and now are being applied widely to improve the quality of products and services in industrial and business sectors. Recently SQC tools, in particular quality control charts, have been used in healthcare surveillance. In some cases, these tools have been modified and developed to better suit the health sector characteristics and needs. It seems that some of the work in the healthcare area has evolved independently of the development of industrial statistical process control methods. Therefore analysing and comparing paradigms and the characteristics of quality control charts and techniques across the different sectors presents some opportunities for transferring knowledge and future development in each sectors. Meanwhile considering capabilities of Bayesian approach particularly Bayesian hierarchical models and computational techniques in which all uncertainty are expressed as a structure of probability, facilitates decision making and cost-effectiveness analyses. Therefore, this research investigates the use of quality improvement cycle in a health vii setting using clinical data from a hospital. The need of clinical data for monitoring purposes is investigated in two aspects. A framework and appropriate tools from the industrial context are proposed and applied to evaluate and improve data quality in available datasets and data flow; then a data capturing algorithm using Bayesian decision making methods is developed to determine economical sample size for statistical analyses within the quality improvement cycle. Following ensuring clinical data quality, some characteristics of control charts in the health context including the necessity of monitoring attribute data and correlated quality characteristics are considered. To this end, multivariate control charts from an industrial context are adapted to monitor radiation delivered to patients undergoing diagnostic coronary angiogram and various risk-adjusted control charts are constructed and investigated in monitoring binary outcomes of clinical interventions as well as postintervention survival time. Meanwhile, adoption of a Bayesian approach is proposed as a new framework in estimation of change point following control chart’s signal. This estimate aims to facilitate root causes efforts in quality improvement cycle since it cuts the search for the potential causes of detected changes to a tighter time-frame prior to the signal. This approach enables us to obtain highly informative estimates for change point parameters since probability distribution based results are obtained. Using Bayesian hierarchical models and Markov chain Monte Carlo computational methods, Bayesian estimators of the time and the magnitude of various change scenarios including step change, linear trend and multiple change in a Poisson process are developed and investigated. The benefits of change point investigation is revisited and promoted in monitoring hospital outcomes where the developed Bayesian estimator reports the true time of the shifts, compared to priori known causes, detected by control charts in monitoring rate of excess usage of blood products and major adverse events during and after cardiac surgery in a local hospital. The development of the Bayesian change point estimators are then followed in a healthcare surveillances for processes in which pre-intervention characteristics of patients are viii affecting the outcomes. In this setting, at first, the Bayesian estimator is extended to capture the patient mix, covariates, through risk models underlying risk-adjusted control charts. Variations of the estimator are developed to estimate the true time of step changes and linear trends in odds ratio of intensive care unit outcomes in a local hospital. Secondly, the Bayesian estimator is extended to identify the time of a shift in mean survival time after a clinical intervention which is being monitored by riskadjusted survival time control charts. In this context, the survival time after a clinical intervention is also affected by patient mix and the survival function is constructed using survival prediction model. The simulation study undertaken in each research component and obtained results highly recommend the developed Bayesian estimators as a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances as well as industrial and business contexts. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The empirical results and simulations indicate that the Bayesian estimators are a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The advantages of the Bayesian approach seen in general context of quality control may also be extended in the industrial and business domains where quality monitoring was initially developed.

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Background: Foot ulcers are a frequent reason for diabetes-related hospitalisation. Clinical training is known to have a beneficial impact on foot ulcer outcomes. Clinical training using simulation techniques has rarely been used in the management of diabetes-related foot complications or chronic wounds. Simulation can be defined as a device or environment that attempts to replicate the real world. The few non-web-based foot-related simulation courses have focused solely on training for a single skill or “part task” (for example, practicing ingrown toenail procedures on models). This pilot study aimed to primarily investigate the effect of a training program using multiple methods of simulation on participants’ clinical confidence in the management of foot ulcers. Methods: Sixteen podiatrists participated in a two-day Foot Ulcer Simulation Training (FUST) course. The course included pre-requisite web-based learning modules, practicing individual foot ulcer management part tasks (for example, debriding a model foot ulcer), and participating in replicated clinical consultation scenarios (for example, treating a standardised patient (actor) with a model foot ulcer). The primary outcome measure of the course was participants’ pre- and post completion of confidence surveys, using a five-point Likert scale (1 = Unacceptable-5 = Proficient). Participants’ knowledge, satisfaction and their perception of the relevance and fidelity (realism) of a range of course elements were also investigated. Parametric statistics were used to analyse the data. Pearson’s r was used for correlation, ANOVA for testing the differences between groups, and a paired-sample t-test to determine the significance between pre- and post-workshop scores. A minimum significance level of p < 0.05 was used. Results: An overall 42% improvement in clinical confidence was observed following completion of FUST (mean scores 3.10 compared to 4.40, p < 0.05). The lack of an overall significant change in knowledge scores reflected the participant populations’ high baseline knowledge and pre-requisite completion of web-based modules. Satisfaction, relevance and fidelity of all course elements were rated highly. Conclusions: This pilot study suggests simulation training programs can improve participants’ clinical confidence in the management of foot ulcers. The approach has the potential to enhance clinical training in diabetes-related foot complications and chronic wounds in general.

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This paper examines the case of a procurement auction for a single project, in which the breakdown of the winning bid into its component items determines the value of payments subsequently made to bidder as the work progresses. Unbalanced bidding, or bid skewing, involves the uneven distribution of mark-up among the component items in such a way as to attempt to derive increased benefit to the unbalancer but without involving any change in the total bid. One form of unbalanced bidding for example, termed Front Loading (FL), is thought to be widespread in practice. This involves overpricing the work items that occur early in the project and underpricing the work items that occur later in the project in order to enhance the bidder's cash flow. Naturally, auctioners attempt to protect themselves from the effects of unbalancing—typically reserving the right to reject a bid that has been detected as unbalanced. As a result, models have been developed to both unbalance bids and detect unbalanced bids but virtually nothing is known of their use, success or otherwise. This is of particular concern for the detection methods as, without testing, there is no way of knowing the extent to which unbalanced bids are remaining undetected or balanced bids are being falsely detected as unbalanced. This paper reports on a simulation study aimed at demonstrating the likely effects of unbalanced bid detection models in a deterministic environment involving FL unbalancing in a Texas DOT detection setting, in which bids are deemed to be unbalanced if an item exceeds a maximum (or fails to reach a minimum) ‘cut-off’ value determined by the Texas method. A proportion of bids are automatically and maximally unbalanced over a long series of simulated contract projects and the profits and detection rates of both the balancers and unbalancers are compared. The results show that, as expected, the balanced bids are often incorrectly detected as unbalanced, with the rate of (mis)detection increasing with the proportion of FL bidders in the auction. It is also shown that, while the profit for balanced bidders remains the same irrespective of the number of FL bidders involved, the FL bidder's profit increases with the greater proportion of FL bidders present in the auction. Sensitivity tests show the results to be generally robust, with (mis)detection rates increasing further when there are fewer bidders in the auction and when more data are averaged to determine the baseline value, but being smaller or larger with increased cut-off values and increased cost and estimate variability depending on the number of FL bidders involved. The FL bidder's expected benefit from unbalancing, on the other hand, increases, when there are fewer bidders in the auction. It also increases when the cut-off rate and discount rate is increased, when there is less variability in the costs and their estimates, and when less data are used in setting the baseline values.

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Twenty first century learners operate in organic, immersive environments. A pedagogy of student-centred learning is not a recipe for rooms. A contemporary learning environment is like a landscape that grows, morphs, and responds to the pressures of the context and micro-culture. There is no single adaptable solution, nor a suite of off-the-shelf answers; propositions must be customisable and infinitely variable. They must be indeterminate and changeable; based on the creation of learning places, not restrictive or constraining spaces. A sustainable solution will be un-fixed, responsive to the life cycle of the components and materials, able to be manipulated by the users; it will create and construct its own history. Learning occurs as formal education with situational knowledge structures, but also as informal learning, active learning, blended learning social learning, incidental learning, and unintended learning. These are not spatial concepts but socio-cultural patterns of discovery. Individual learning requirements must run free and need to be accommodated as the learner sees fit. The spatial solution must accommodate and enable a full array of learning situations. It is a system not an object. Three major components: 1. The determinate landscape: in-situ concrete 'plate' that is permanent. It predates the other components of the system and remains as a remnant/imprint/fossil after the other components of the system have been relocated. It is a functional learning landscape in its own right; enabling a variety of experiences and activities. 2. The indeterminate landscape: a kit of pre-fabricated 2-D panels assembled in a unique manner at each site to suit the client and context. Manufactured to the principles of design-for-disassembly. A symbiotic barnacle like system that attaches itself to the existing infrastructure through the determinate landscape which acts as a fast growth rhizome. A carapace of protective panels, infinitely variable to create enclosed, semi-enclosed, and open learning places. 3. The stations: pre-fabricated packages of highly-serviced space connected through the determinate landscape. Four main types of stations; wet-room learning centres, dry-room learning centres, ablutions, and low-impact building services. Entirely customised at the factory and delivered to site. The stations can be retro-fitted to suit a new context during relocation. Principles of design for disassembly: material principles • use recycled and recyclable materials • minimise the number of types of materials • no toxic materials • use lightweight materials • avoid secondary finishes • provide identification of material types component principles • minimise/standardise the number of types of components • use mechanical not chemical connections • design for use of common tools and equipment • provide easy access to all components • make component size to suite means of handling • provide built in means of handling • design to realistic tolerances • use a minimum number of connectors and a minimum number of types system principles • design for durability and repeated use • use prefabrication and mass production • provide spare components on site • sustain all assembly and material information

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Biosequestration of carbon in trees, forests and vegetation is a key method for offsetting greenhouse gas emissions. To facilitate it, the Commonwealth has introduced the Carbon Farming Initiative, a scheme whereby carbon credits can be earned for biosequestration offsets projects. The project proponent must acquire under state law a ‘carbon sequestration right’ which confers the benefit of the sequestered carbon on the land. Each State provides for an agreement associated with the carbon sequestration right between the landowner and the holder of the right (‘carbon sequestration agreement’). This article identifies some key risks and issues that must be considered in the drafting of a carbon sequestration agreement to support the successful operation of a biosequestration offsets project.