The stability and formulation of topical analgesics

High-performance liquid chromatographic methods are developed for the simultaneous determination of various salicylates, their p-hydroxy isomers and nicotinic acid esters. The method is sensitive enough to detect trace amounts (~µM/L)of the product generated from cross reactivity between the drugs and the vehicle. The developed method also allows analysis of various topical products containing salicylate and nicotinate esters in their formulations. Applying this method, the degradation profiles of salicylates, nicotinates, p-hydroxy benzoate, o-methoxy benzoate and aspirin prodrugs in alkaline media are determined. The profile for alkyl salicylate degradation is found to be first order (A---? B) When the alcoholic radical is similar to that of the ester. In alcohol having a radical different from that of the ester function, the degradation is found to proceed through competitive transesterification and hydrolysis. The intermediates are identified following synthesis and isolation. The rate and extent of transesterification depends on the proportion of alcohol present in the system. Equations are presented to model the time profiles of reactant and product concentration. The reactions are base catalysed and the predominant pathway involves a concerted solvent attack upon the salicylate anion. Competitive hydrolysis of both ester components also follows this mechanism at moderate pH values but rates increase under strongly alkaline conditions as direct hydroxide attack becomes significant. In contrast, transesterification is independent of base concentration once full ionization is accomplished. The competitive hydrolysis is modelled using equations involving the dielectric constant of the medium. A range of other esters are also shown to undergo base-catalysed transesterification. In non-alcoholic solution phenyl salicylate undergoes a concentration-dependent oligomerisation which yields salsalate among the products. Competitive transesterification and hydrolysis also occur in products for topical use which have vehicles based upon alcohol, glycol or glycol polymers. Such reactions may compromise stability assessments, pharmaceutical integrity and delivery profiles.

Gas-metal reactions and porosity in the inert gas arc welding of copper

A study has been made of the effects of welding and material variables on the occurrence of porosity in tungsten inert gas arc welding of copper. The experiments were based on a statistical design and variables included, welding current, welding speed, arc atmosphere composition, inert gas flow rate, weld preparation, and base material. The extent of weld metal porosity was assessed by density measurement and its morphology by X-ray radiography and metallography. In conjunction with this the copper-steam reaction has been investigated under conditions of controlled atmosphere arc melting. The welding experiments have shown that the extent of steam porosity is increased by increased water vapour content of the arc atmosphere, increased oxygen content of the base material and decreased welding speed. The arc melting experiments have shown that the steam reaction occurs in the body of the weld pool and proceeds to an apparent equi1ibrium state appropriate to to its temperature, the hydrogen and oxygen being supplied by the dissociation of water vapour in the arc atmosphere. It has been shown conclusively that nitrogen porosity can occur in the tungsten inert gas arc welding of copper and that this porosity can be eliminated by using filler wires containing small amounts of aluminum and titanium. Since it has been shown to be much more difficult to produce sound butt welds than melt runs it has been concluded that the porosity associated with joint fit up is due to nitrogen entrained into tho arc atmosphere. Clearly atmospheric entrainment would also, to a much lesser extent, involve water vapour. From a practical welding point of view it has thus been postulated that use of a filler wire containing small amounts of aluminum and/or titanium would eliminate both forms of porosity since these elements are both strongJy deoxidising and denitriding.

Minority influence and optimal problem-solving

An analogous thinking task was used to test Nemeth's Convergent–Divergent theory of majority and minority influence. Participants read a (base) problem and one of three solutions (one of which is considered the ‘best' solution). They then generated solutions to a second (target) problem which shared similar structural features to the first problem. Due to the similarities between problems, the solution given to the first problem can be used as an analogy in solving the second. In contrast to Nemeth's theory, when the solution to the base problem was endorsed by a numerical majority there was not an increase in analogy-transfer in solving the target problem. However, in support of Nemeth's theory, when the base solution was supported by a numerical minority then the participants were more likely to generate the ‘best' solution to the target problem regardless of which base solution they were given. Copyright © 1999 John Wiley & Sons, Ltd.

Monetary variability and monetary variables in the Franc zone

Failure to detect or account for structural changes in economic modelling can lead to misleading policy inferences, which can be perilous, especially for the more fragile economies of developing countries. Using three potential monetary policy instruments (Money Base, M0, and Reserve Money) for 13 member-states of the CFA Franc zone over the period 1989:11-2002:09, we investigate the magnitude of information extracted by employing data-driven techniques when analyzing breaks in time-series, rather than the simplifying practice of imposing policy implementation dates as break dates. The paper also tests Granger's (1980) aggregation theory and highlights some policy implications of the results.

Modeling and validating dynamic adaptation

This paper discusses preliminary work on modeling and validation dynamic adaptation. The proposed approach is on the use of aspect-oriented modeling (AOM) and models at runtime. Our approach covers design and runtime phases. At design-time, a base model and different variant architecture models are designed and the adaptation model is built. Crucially, the adaptation model includes invariant properties and constraints that allow the validation of the adaptation rules before execution. During runtime, the adaptation model is processed to produce a correct system configuration that can be executed.

The global audit profession and the international financial architecture:understanding regulatory relationships at a time of financial crisis

This paper explores how regulatory relationships in the global audit arena are being affected by the current financial crisis. Key policy initiatives and debates are analyzed, along with institutional interactions, in particular between the International Federation of Accountants (IFAC), international regulators and the large audit firms. The events are placed in the context of the new international financial architecture which has developed over the last decade. Using the illustrative lens of bank auditing, questions are asked of the nature and status of audit practice and the regulatory arrangements governing such practice. The paper shows the active nature of the regulatory responses to the crisis and the shifting and competing influences among key regulatory and professional participants in the global audit arena. Emphasis is placed on the need for audit researchers to be sensitive to the developing global financial architecture, and its potential implications for the study of audit practice in different national and international contexts.

Modelling short crack growth behaviour in nickel-base superalloys

This paper provides a description of the features and mechanisms of facetted short crack growth in Ni-base superalloys, and briefly reviews existing short crack growth models in terms of their application to Ni-base alloys. The concept of “soft barriers” is introduced to produce a new two-phase model for local microstructural effects on short crack growth in Waspaloy. This is derived from detailed observations of crack growth through individual grains. The model differs from all previous approaches in highlighting the importance of crack path perturbations within grains. Potential applications of the model in alloy development are discussed.

Evaluation of the activity and stability of alkali-doped metal oxide catalysts for application to an intensified method of biodiesel production

A series of alkali-doped metal oxide catalysts were prepared and evaluated for activity in the transesterification of rapeseed oil to biodiesel. Of those evaluated, LiNO3/CaO, NaNO3/CaO, KNO3/CaO and LiNO3/MgO exhibited >90% conversion in a standard 3 h test. There was a clear correlation between base strength and activity. These catalysts appeared to be promising candidates to replace conventional homogeneous catalysts for biodiesel production as the reaction times are low enough to be practical in continuous processes and the preparations are neither prohibitively difficult nor costly. However, metal leaching from the catalyst was detected, and this resulted in some homogeneous activity. This would have to be resolved before these catalysts would be viable for large-scale biodiesel production facilities.

Servitization and competitive advantage:the importance of organizational structure and value chain position

Servitization represents a business-model change and organizational transformation from selling goods to selling an integrated combination of goods and services. Competitive advantage is one outcome of this shift. During servitization, companies follow stages to realize services as an opportunity to differentiate from goods and achieve higher customer satisfaction. This study analyzes this transition from base, intermediate, and advanced services by presenting results from 102 senior executives in multinational companies. Our results suggest increasing interest in service-led strategies in manufacturing companies. The results also show that increasing differentiation and high customer satisfaction are fundamental to achieving competitive advantage and superior performance with services. The analysis also indicates the importance of a company’s position in the value chain and the organizational structure it selects to support services in successful servitization.

A new VRPPD model and a hybrid heuristic solution approach for e-tailing

We analyze a business model for e-supermarkets to enable multi-product sourcing capacity through co-opetition (collaborative competition). The logistics aspect of our approach is to design and execute a network system where “premium” goods are acquired from vendors at multiple locations in the supply network and delivered to customers. Our specific goals are to: (i) investigate the role of premium product offerings in creating critical mass and profit; (ii) develop a model for the multiple-pickup single-delivery vehicle routing problem in the presence of multiple vendors; and (iii) propose a hybrid solution approach. To solve the problem introduced in this paper, we develop a hybrid metaheuristic approach that uses a Genetic Algorithm for vendor selection and allocation, and a modified savings algorithm for the capacitated VRP with multiple pickup, single delivery and time windows (CVRPMPDTW). The proposed Genetic Algorithm guides the search for optimal vendor pickup location decisions, and for each generated solution in the genetic population, a corresponding CVRPMPDTW is solved using the savings algorithm. We validate our solution approach against published VRPTW solutions and also test our algorithm with Solomon instances modified for CVRPMPDTW.

Enhanced connectivity and QoE through LTE-WiFi interworking in Smart Cities

Mobile communication and networking infrastructures play an important role in the development of smart cities, to support real-time information exchange and management required in modern urbanization. Mobile WiFi devices that help offloading data traffic from the macro-cell base station and serve the end users within a closer range can significantly improve the connectivity of wireless communications between essential components including infrastructural and human devices in a city. However, this offloading function through interworking between LTE and WiFi systems will change the pattern of resource distributions operated by the base station. In this paper, a resource allocation scheme is proposed to ensure stable service coverage and end-user quality of experience (QoE) when offloading takes place in a macro-cell environment. In this scheme, a rate redistribution algorithm is derived to form a parametric scheduler to meet the required levels of efficiency and fairness, guided by a no-reference quality assessment metric. We show that the performance of resource allocation can be regulated by this scheduler without affecting the service coverage offered by the WLAN access point. The performances of different interworking scenarios and macro-cell scheduling policies are also compared.

Does Lost Time Cost You Money and Create High Risk?

The aim of the case study is to express the delayed repair time impact on the revenues and profit in numbers with the example of the outage of power plant units. Main steps of risk assessment: • creating project plan suitable for risk assessment • identification of the risk factors for each project activities • scenario-analysis based evaluation of risk factors • selection of the critical risk factors based on the results of quantitative risk analysis • formulating risk response actions for the critical risks • running Monte-Carlo simulation [1] using the results of scenario-analysis • building up a macro which creates the connection among the results of the risk assessment, the production plan and the business plan.

Hurricane Wilma’s impact on overall soil elevation and zones within the soil profile in a mangrove forest

Soil elevation affects tidal inundation period, inundation frequency, and overall hydroperiod, all of which are important ecological factors affecting species recruitment, composition, and survival in wetlands. Hurricanes can dramatically affect a site’s soil elevation. We assessed the impact of Hurricane Wilma (2005) on soil elevation at a mangrove forest location along the Shark River in Everglades National Park, Florida, USA. Using multiple depth surface elevation tables (SETs) and marker horizons we measured soil accretion, erosion, and soil elevation. We partitioned the effect of Hurricane Wilma’s storm deposit into four constituent soil zones: surface (accretion) zone, shallow zone (0–0.35 m), middle zone (0.35–4 m), and deep zone (4–6 m). We report expansion and contraction of each soil zone. Hurricane Wilma deposited 37.0 (±3.0 SE) mm of material; however, the absolute soil elevation change was + 42.8 mm due to expansion in the shallow soil zone. One year post-hurricane, the soil profile had lost 10.0 mm in soil elevation, with 8.5 mm of the loss due to erosion. The remaining soil elevation loss was due to compaction from shallow subsidence. We found prolific growth of new fine rootlets (209 ± 34 SE g m−2) in the storm deposited material suggesting that deposits may become more stable in the near future (i.e., erosion rate will decrease). Surficial erosion and belowground processes both played an important role in determining the overall soil elevation. Expansion and contraction in the shallow soil zone may be due to hydrology, and in the middle and bottom soil zones due to shallow subsidence. Findings thus far indicate that soil elevation has made substantial gains compared to site specific relative sea-level rise, but data trends suggest that belowground processes, which differ by soil zone, may come to dominate the long term ecological impact of storm deposit.

Instability of CTG Repeats is Governed by the Position of a DNA Base Lesion through Base Excision Repair

Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegeneration and cancer. However, their underlying mechanisms remain to be elucidated. Recent studies have demonstrated that CAG repeat expansions can be initiated by oxidative DNA base damage and fulfilled by base excision repair (BER), suggesting active roles for oxidative DNA damage and BER in TNR instability. Here, we provide the first evidence that oxidative DNA damage can induce CTG repeat deletions along with limited expansions in human cells. Biochemical characterization of BER in the context of (CTG)20 repeats further revealed that repeat instability correlated with the position of a base lesion in the repeat tract. A lesion located at the 59-end of CTG repeats resulted in expansion, whereas a lesion located either in the middle or the 39-end of the repeats led to deletions only. The positioning effects appeared to be determined by the formation of hairpins at various locations on the template and the damaged strands that were bypassed by DNA polymerase b and processed by flap endonuclease 1 with different efficiency. Our study indicates that the position of a DNA base lesion governs whether TNR is expanded or deleted through BER.

Advanced Placement and American education: A Foucauldian analysis of the Advanced Placement Program of the college board

Advanced Placement is a series of courses and tests designed to determine mastery over introductory college material. It has become part of the American educational system. The changing conception of AP was examined using critical theory to determine what led to a view of continual success. The study utilized David Armstrong's variation of Michel Foucault's critical theory to construct an analytical framework. Black and Ubbes' data gathering techniques and Braun and Clark's data analysis were utilized as the analytical framework. Data included 1135 documents: 641 journal articles, 421 newspaper articles and 82 government documents. ^ The study revealed three historical ruptures correlated to three themes containing subthemes. The first rupture was the Sputnik launch in 1958. Its correlated theme was AP leading to school reform with subthemes of AP as reform for able students and AP's gaining of acceptance from secondary schools and higher education. The second rupture was the Nation at Risk report published in 1983. Its correlated theme was AP's shift in emphasis from the exam to the course with the subthemes of AP as a course, a shift in AP's target population, using AP courses to promote equity, and AP courses modifying curricula. The passage of the No Child Left Behind Act of 2001 was the third rupture. Its correlated theme was AP as a means to narrow the achievement gap with the subthemes of AP as a college preparatory program and the shifting of AP to an open access program. ^ The themes revealed a perception that progressively integrated the program into American education. The AP program changed emphasis from tests to curriculum, and is seen as the nation's premier academic program to promote reform and prepare students for college. It has become a major source of income for the College Board. In effect, AP has become an agent of privatization, spurring other private entities into competition for government funding. The change and growth of the program over the past 57 years resulted in a deep integration into American education. As such the program remains an intrinsic part of the system and continues to evolve within American education. ^