Abstract Mineral replacement reactions are common in the various environments where rocks have undergone re-equilibration with geologic fluids. Replacement reactions commonly take the form of fluid-aided, coupled dissolution-precipitation and often result in pseudomorph formation. One class of environment that frequently shows significant examples of mineral replacements is hydrothermal ore deposit systems. The goal of this study was to test the simultaneous reactivity of fluorapatite and monazite in Na- and Si-rich hydrothermal fluids, which partially mimic the mineralogy and fluid chemistry of the Llallagua tin deposit in Bolivia. A series of experiments were performed at 300 to 600 °C and 100 MPa, utilizing various combinations of monazite, fluorapatite, and H2O + Na2Si2O5. Reaction products were evaluated using scanning electron microscopy, electron microprobe analysis, and single-crystal X-ray diffraction. The results of this experimental study show that fluorapatite and monazite are differentially reactive under the conditions studied. The reaction products, pathways, and kinetics have a large temperature dependence. The 300 and 400 °C experiments show variable amounts of monazite replacement and only minor, if any, dissolution or reactivity of fluorapatite. The high-temperature 500 and 600 °C experiments are characterized by massive replacement of monazite by vitusite and britholite. Exclusively at 600 °C, monazite alteration takes the form of symplectite development at the reaction front as vermicular intergrowths of vitusite and britholite. The higher-temperature experiments also show substantially more reactivity by fluorapatite, which is partially pseudomorphically altered into britholite. This is an example of regenerative mineral replacement where both fluorapatite and britholite share the same atomic structure and are crystallographically coherent after the partial replacement. The britholite replacement is characterized by the presence of oriented nanochannels, which facilitate fluid-based mass transfer between the bulk solution and the reaction front. The fluorapatite replacement is enhanced by monazite alteration through a self-perpetuating, positive feedback mechanism between these two reactions, which enhance the REE mobility in alkali-bearing fluids and further drives bulk re-equilibration. These results have potential geochronologic implications and may be significant in the evaluation of monazite and fluorapatite as potential solid nuclear waste forms. They also give us deeper insights into the mechanism of mineral replacement reactions and porosity development.


We describe Chronicle, a new system that allows users to explore document workflow histories. Chronicle captures the entire video history of a graphical document, and provides links between the content and the relevant areas of the history. Users can indicate specific content of interest, and see the workflows, tools, and settings needed to reproduce the associated results, or to better understand how it was constructed to allow for informed modification. Thus, by storing the rich information regarding the document's history workflow, Chronicle makes any working document a potentially powerful learning tool. We outline some of the challenges surrounding the development of such a system, and then describe our implementation within an image editing application. A qualitative user study produced extremely encouraging results, as users unanimously found the system both useful and easy to use.


This paper describes the distinct tonal configurations of wh-questions in Spanish and discusses their possible correlations with pragmatic and interactional meanings. The data consisted of both read and spontaneous speech from four Latin American varieties. Two of the dialects, Mexican and Colombian, as opposed to Venezuelan and Puerto Rican, showed a marked preference for rising contours in read speech, while in interviews virtually no such contours occurred for any of the speakers. A different kind of rising contour did regularly occur in the natural speech data, a globally rising contour without a dip before the final high rise, used for confirmation or reprise whquestions. The conclusion of this study is that the unmarked configuration is indeed the gradually descending one, as described in the literature. This applies to all the dialects here examined, in spite of the variability of the contours, which is context-induced and related to information structure.


The problem of time of death (TOD) estimation by body cooling is revisited by proposing a nonlinear least squares approach that takes as input a series of temperature readings only. Using a reformulation of the Marshall–Hoare double exponential formula and a technique for reducing the dimension of the state space, an error function that depends on the two cooling rates is constructed, with the aim of minimizing this function. Standard nonlinear optimization methods that are used to minimize the bivariate error function require an initial guess for these unknown rates. Hence, a systematic procedure based on the given temperature data is also proposed to determine an initial estimate for the rates. Then, an explicit formula for the TOD is given. Results of numerical simulations using both theoretical and experimental data are presented, both yielding reasonable estimates. The proposed procedure does not require knowledge of the temperature at death nor the body mass. In fact, the method allows the estimation of the temperature at death once the cooling rates and the TOD have been calculated. The procedure requires at least three temperature readings, although more measured readings could improve the estimates. With the aid of computerized recording and thermocouple detectors, temperature readings spaced 10–15 min apart, for example, can be taken. The formulas can be straightforwardly programmed and installed on a hand‐held device for field use.


Space densities and birthrates of Planetary Nebulae (PNe) are highly uncertain. A large range of formation rates has been derived by different studies, which has led to contradicting ideas for the final evolutionary phases of low and intermediate mass stars. We started a project to deduce a birthrate using a sample of PNe within 2 kpc. The central stars will be identified in the PNe fields by their photometric colours and then used to establish improved distance estimates. To facilitate this we have created grids of photometric colours which are used to constrain stellar parameters. Our study has concentrated on PNe in SDSS and the INT Photometric Hα Survey (IPHAS) so far. IPHAS is a nearly complete northern galactic plane survey in Hα, r' and i' bands. Many previously unknown PNe have been discovered with IPHAS. We investigate implications of a more complete local sample on PN birthrate estimates.


In an effort to establish new benzimidazole related structural leads with improved anticancer activity, several new benzimidazole derivatives (5a-i) with 1,3,4-oxadiazole scaffold incorporated were synthesized and studied for their anticancer activity. The anticancer screening against MDA-MB-231 breast cancer cell lines showed that compound (5c) exhibited moderate cytotoxicity.


In the years between 1930 and 1980, some of the best-known photographers from around the world came to London and made its streets, buildings and communities their subject. For some, the British capital was to become home; for others it remained a foreign city, as enigmatic perhaps as any they had visited. Each brought their own distinctive perspective,subverting or perpetuating national stereotypes, seeking out the typical or the exotic, attempting to penetrate the fabled British reserve with their lens. Together their work creates a portrait of a great world city, changing and mutating, a restless and fascinating muse. This remarkable book, accompanying a major exhibition at Tate Britain in London's Olympic year, demonstrates the breadth and variety of the responses London provoked from visiting photographers during the period, from portraits to reportage, from social realism to whimsy and humour, the changes in their technique and attitude demonstrating developments in photography itself. Essays by selected critics will address both the photographers' contributions and the history of London. Artists represented feature some of the greatest names in twentieth century photography, including Eve Arnold, Dorothy Bohm, Bill Brandt, Henri-Cartier Bresson, Bruce Davidson, Elliot Erwitt, Robert Frank, Leonard Freed, Emil Hoppe,Inge Morath, Dora Maar, Irving Penn, Willy Ronis and Al Vandenberg.


This paper deals with the modeling of a regional energy system, based on the example of Qatar, over a time horizon of 35 years or more, taking into account the possible transition toward a smart city paradigm of the Doha region and the probable climate regime that could result from COP21 and the coming rounds of international climate negotiations. The impact on the energy system of a transition toward smart city could take many forms: (i) by providing two-way communications between consumers and electricity producers, the smart city will foster demand response and distributed energy resource management; (ii) new forms of demand for energy services will materialize in the transport, housing and service sectors that could contribute to lower the environmental footprint of the energy sector; (iii) the smart-grid connection of distributed energy resources and the possibility to provide secondary reserve through grid storage and distributed system service, like e.g. reactive power compensation, will facilitate the penetration of variable renewable energy in the energy system. Qatar is the world-class leader in the export of liquefied natural gas (LNG). It has also access to crude oil reserves. As the economy of Qatar developed, as in other Gulf countries, the energy system expanded assuming an unlimited supply of very low cost fossil fuels. However, the very economic success of the gas and oil exporting countries in the Gulf region is starting to impose a limit on this form of development of the energy system. The share of gas that is used in the region and thus not available for export is increasing sharply. The local pollution due to the burning of fossil fuels in transport, residential, service and industry sectors, has to be curbed. Finally, at COP21 in Paris, more than 160 nations, including Qatar, have agreed to reduce GHG emissions in order to reach a goal of limiting the temperature change at the end of 21st century at 1.5oC. At COP21 Qatar has made a commitment to reduce its per-capita emission level, which is one of the highest in the world. To deal with these challenges, the Gulf countries count on a substitution from fossil fuel source to variable renewable ones (as well as some extent to nuclear power generation in UAE, KSA and Iran). This is exemplified by the location of IRENA headquarters[1] in Abu Dhabi, inaugurated in May 2015. Indeed, harnessing wind and solar energy sources seems promising in the region, with some caveats due to intermittency of wind blowing and sand storms reducing the efficiency of solar panels. There is another game changing phenomenon represented by the drive toward smart cities. The cities in Gulf countries are very modern and they are ready to embrace the smart city paradigm and concept. Abu Dhabi and more generally the UAE, Qatar and Saudi Arabia have announced pilot projects for fully integrated "smart-city" districts. The development of the "internet of things", which characterizes smart cities, will translate for the energy system into a development of smart-grid connected, distributed energy resources and this should help tremendously the penetration of variable renewable energy sources. The model ETEM-SC[2] used in this research has been designed to help in assessing the policies that could be used to define, up to the horizon 2050, an environmentally friendly energy system in Qatar. ETEM-SC is a technology rich cost-efficiency model, which permits an exploration of the future of the regional energy system under different environmental and economic constraints. The model is derived from the shell-model ETEM (Energy-Technology-Environment-Model), developed at ORDECSYS[3]. This shell has a structure of a linear program, as in MARKAL, MESSAGE or TIMES, with an extensive description of technology and energy choices in the region into consideration. The new additions that have been made for our purpose (SC for Smart Cities) concern: (i) the modeling of constraints and options at the power distribution level, due to the introduction of smart grids, distributed energy resource and demand response; (ii) the consideration of the impact on demand for energy services of the development of a smart city environment, and (iii) the explicit consideration of uncertainty in the scenario building, through the use of stochastic programming and robust optimization techniques. Some technical aspects of these modeling advances have been described in two parent papers (Babonneau et al. (2016a) and (2016b)). The present research will focus on the description of the scenarios for Qatar that result from the use of this model. These scenarios are based on publicly available data and should not be considered as a representation of the energy policy of the state of Qatar. The purpose of this exercise is to demonstrate the potential offered by ETEM-SC to assess the possible penetration of variable renewable energy in regional energy systems with smart-city development, in order to reduce drastically the GHG emissions. [1] The International Renewable Energy Agency. www.irena.org [2] Energy Technology Environment Model-Smart-Cities. [3] See www.ordecsys.com for details.


The main purpose of this thesis is the development of a new constitutive soil model emphasising the use of thermodynamic principles. This new approach to plasticity modelling, termed 'hyperplasticity', was first developed by Collins and Houlsby (1997) and Houlsby and Puzrin (2000). This idea has been further extended to continuous hyperplasticity in which smooth transitions between elastic and plastic behaviour can be modelled (Puzrin and Houlsby, 2001b). Applying hyperplasticity to this research, a kinematic hardening model specified by means of two scalar functionals is used to accommodate the effect of stress history on stiffness. A rate-dependent calculation for an approximation of the incremental stress-strain response is introduced. The model developed in the research is named 'kinematic hardening modified Cam-clay (KHMCC) model' and requires eight parameters (plus an extra parameter for rate-dependent analysis). Triaxial test results from the Asian Institute of Technology (AIT) and cyclic undrained triaxial data from Chulalongkorn University are employed to establish the soil parameters for the new model. The model is initially developed in terms of triaxial stress-strain parameters for the purpose of comparison with the experimental data on Bangkok clay. The model is expressed in FORTRAN code for implementation into the OXFEM finite element program. Two examples of real geotechnical projects in Bangkok (a road embankment and tunnelling in soft ground) are analysed under plane strain conditions. Comparisons of the numerical analysis results with field data are made. In addition, factors affecting the results of the analysis such as stress history and K0, are investigated.


Data from studies in Mwanza Region in Tanzania suggest stabilising HIV prevalence. The objective was to determine the factors that may have contributed to the relatively stable pattern of the HIV prevalence observed in the comparison communities of the Mwanza STD treatment trial in rural Mwanza Region, Tanzania between 1991 and 2001. Socio-demographic, sexual behaviour and HIV prevalence data in two surveys conducted 10 years apart in the same communities using similar sampling schemes were compared. The age standardised HIV prevalence was 3.8% (95% CI: 3.2-4.6) in 1991 and 4.3% (95% CI: 2.8-6.4) in 2001 for males (Z= - 0.56, P= 0.58); and 4.5% (95% CI: 3.8-5.3) in 1991 and 3.9% (95% CI: 2.6-5.6) in 2001 for females (Z= 0.64, P = 0.52). Participants in the 2001 survey reported significantly fewer lifetime and recent sexual partners (12 months), Sexually Transmitted disease syndromes (12 months) and significantly more condom use at last sex with casual partners than those in the 1991 behaviour survey. We conclude that STD/HIV infection prevention activities in rural Mwanza may be responsible for changes in risky sexual behaviour and have successfully impeded the spread of HIV infection. These activities should therefore be enhanced to reduce HIV incidence even further. In addition, modelling studies are needed to assess whether mobility of HIV infected people out of rural communities may stabilise the prevalence of the HIV infection in the general populations.


The various doctrines of subject-matter jurisdiction represent some of the most important limitations on the powers of the federal judiciary, and the Supreme Court has repeatedly said that Article III standing, which enforces the Constitution's "case or controversy" requirement, is the most important of these jurisdictional doctrines. So a federal court that exercises its coercive power over litigants by entering a final judgment without first ensuring that the plaintiff has Article III standing would plainly violate the separation of powers. This much should be indisputable. But what if a federal court exercises its coercive power over litigants before entry of final judgment — say, by unlocking the doors to general discovery that is likely to be so expensive that it effectively coerces the defendant into an in terrorem settlement of a weak claim? Simple logic would suggest that the court should correspondingly shift earlier its resolution of the plaintiff's Article III standing as well. Yet courts inexplicably defer resolving contested issues of standing when raised by defendants, instead treating Article III standing as if it were just another merits issue: something to be plausibly alleged in a complaint, supported by substantial evidence (taken as true) at summary judgment, and eventually proved by a preponderance of evidence at trial. We argue that this approach is wrong, because it potentially subjects litigants to years of coercive proceedings absent a genuine case or controversy. Instead, we propose that courts exclusively and definitively resolve contested issues of Article III standing, no matter when they arise in the litigation, using Rule 12(b)(1) of the Federal Rules of Civil Procedure — including by holding evidentiary hearings and making credibility determinations as necessary. This approach would ensure that courts do not stray beyond the constitutionally dictated boundaries of their power by coercively affecting the primary conduct of litigants without first ensuring the existence of a genuine case or controversy.


The desire to create novel computing systems, paired with recent advances in neuroscientific understanding of the brain, has led researchers to develop neuromorphic architectures that emulate the brain. To date, such models are developed, trained, and deployed on the same substrate. However, excessive co-dependence between the substrate and the algorithm prevents portability, or at the very least requires reconstructing and retraining the model whenever the substrate changes. This paper proposes a well-defined abstraction layer -- the Neuromorphic instruction set architecture, or NISA -- that separates a neural application's algorithmic specification from the underlying execution substrate, and describes the Aivo framework, which demonstrates the concrete advantages of such an abstraction layer. Aivo consists of a NISA implementation for a rate-encoded neuromorphic system based on the cortical column abstraction, a state-of-the-art integrated development and runtime environment (IDE), and various profile-based optimization tools. Aivo's IDE generates code for emulating cortical networks on the host CPU, multiple GPGPUs, or as boolean functions. Its runtime system can deploy and adaptively optimize cortical networks in a manner similar to conventional just-in-time compilers in managed runtime systems (e.g. Java, C#).
 We demonstrate the abilities of the NISA abstraction by constructing a cortical network model of the mammalian visual cortex, deploying on multiple execution substrates, and utilizing the various optimization tools we have created. For this hierarchical configuration, Aivo's profiling based network optimization tools reduce the memory footprint by 50% and improve the execution time by a factor of 3x on the host CPU. Deploying the same network on a single GPGPU results in a 30x speedup. We further demonstrate that a speedup of 480x can be achieved by deploying a massively scaled cortical network across three GPGPUs. Finally, converting a trained hierarchical network to C/C++ boolean constructs on the host CPU results in 44x speedup.


Under normal physiological conditions, tissue remodeling in response to injury leads to tissue regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis - or the excess accumulation of ECM - can disrupt tissue architecture and function. Several organs, including the heart, lung and kidney, exhibit age-associated fibrosis. Here we investigated whether fibrosis underlies aging in the ovary - an organ that ages chronologically before other organs. We used Picrosirius Red (PSR), a connective tissue stain specific for collagen I and III fibers, to evaluate ovarian fibrosis. Using bright-field, epifluorescence, confocal and polarized light microscopy, we validated the specific staining of highly ordered PSR-stained fibers in the ovary. We next examined ovarian PSR staining in two mouse strains (CD1 and CB6F1) across an aging continuum and found that PSR staining was minimal in ovaries from reproductively young adult animals, increased in distinct foci in animals of mid-to-advanced reproductive age, and was prominent throughout the stroma of the oldest animals. Consistent with fibrosis, there was a reproductive age-associated increase in ovarian hydroxyproline content. We also observed a unique population of multinucleated macrophage giant cells, which are associated with chronic inflammation, within the ovarian stroma exclusively in reproductively old mice. In fact, several genes central to inflammation had significantly higher levels of expression in ovaries from reproductively old mice relative to young mice. These results establish fibrosis as an early hallmark of the aging ovarian stroma, and this altered microenvironment may contribute to the age-associated decline in gamete quality.


HNPCC is an autosomal dominantly inherited disorder with proclivity to early onset colorectal cancer in the absence of multiple polyps of the colon. There is a predilection for proximal colonic location (70 per cent) and an excess of synchronous and metachronous colorectal cancers. HNPCC is subdivided into Lynch syndrome I, which is restricted to site-specific colon cancer susceptibility, and Lynch syndrome II, which shows all of the features of Lynch syndrome I, but in addition, patients are at inordinately increased risk for carcinoma of the endometrium, ovary, and other anatomic sites. The frequency of HNPCC is conservatively estimated to be 4 to 6 per cent of the total colorectal cancer burden. Because of the fact that the family history is underreported almost uniformly in medical practice, we believe that the true frequency of this disease may be much greater. Heterogeneity may be extant with respect to tumor association, in that in certain Lynch syndrome II kindreds, carcinoma of the pancreas, kidney, breast, and other anatomic sites may predominate. Knowledge of the natural history of HNPCC predicates surveillance and management strategies. Thus, because of the early onset of and proximal predilection for colorectal cancer, we recommend initiation of colonscopy at age 25 and annually thereafter. We also recommend guaiac testing of the stool at least twice a year. In the case of Lynch syndrome II, in addition to colonscopy, we recommend intensive surveillance for the endometrium, including aspiration biopsies. Other targeted organs, depending on the tumor spectrum in the family, should be given priority attention. Because of an excess of synchronous and metachronous colorectal cancer in HNPCC, subtotal colectomy with ileorectal anastomosis is the treatment of choice for initial colorectal cancer. In women presenting with initial colorectal cancer who have completed their families, consideration should be given to prophylactic hysterectomy and bilateral salpingo-oophorectomy at the time of surgery for colorectal cancer. Needed are biomarkers of acceptable sensitivity and specificity for the genotype, because HNPCC lacks premonitory physical signs. We believe that increased knowledge about colorectal cancer etiology and carcinogenesis can be attained through the study of families prone to the Lynch syndromes.


ABSTRACT The yeast retrotransposon Ty5 preferentially integrates into regions of silent chromatin. Ty5 cDNA also recombines with homologous sequences, generating tandem elements or elements that have exchanged markers between cDNA and substrate. In this study, we demonstrate that Ty5 integration depends upon the conserved DD(35)E domain of integrase and cis-acting sequences at the end of the long terminal repeat (LTR) implicated in integrase binding. cDNA recombination requires Rad52p, which is responsible for homologous recombination. Interestingly, Ty5 cDNA recombines at least three times more frequently with substrates in silent chromatin than with a control substrate at an internal chromosomal locus. This preference depends upon the Ty5 targeting domain that is responsible for integration specificity, suggesting that localization of cDNA to silent chromatin results in the enhanced recombination. Recombination with a telomeric substrate occasionally generates highly reiterated Ty5 arrays, and mechanisms for tandem element formation were explored by using a plasmid-based recombination assay. Point mutations were introduced into plasmid targets, and recombination products were characterized to determine recombination initiation sites. Despite our previous observation of the importance of the LTR in forming tandem elements, recombination cannot simply be explained by crossover events between the LTRs of substrate and cDNA. We propose an alternative model based on single-strand annealing, where single-stranded cDNA initiates tandem element formation and the LTR is required for strand displacement to form a looped intermediate. Retrotransposons are increasingly found associated with chromosome ends, and amplification of Ty5 by both integration and recombination exemplifies how retroelements can contribute to telomere dynamics.


Place attachment is one of the levels of the individuals' relationship with the place and it leads to the improvement in the behavioral and scientific performance of the university students by influencing their behavior and controlling their negative behavioral patterns in an academic environment. This is while the environmental factors influencing this sense depend on the type of a place's performance and the recognition of these factors, especially in academic spaces, in addition to the contribution to the enhancement of the designing quality of the academic spaces, assists the universities' officials, as well, in accomplishing one of their essential goals, i.e. the elevation of the university's academic level. Thus, the place attachment and its aspects were explained to identify these factors in the university environment using the correlation method based on the existing literature in this area and the assumed effective factors in the creation of place attachment in three aspects of functional, physical and social particularly in university spaces were studied within the format of the theoretical model. Then, to test the model, 373 university students were selected from the technical-engineering, art and architecture and basic sciences departments of Islamic Azad University, South Tehran Branch, based on random-clustering method following which the researcher-made questionnaires were distributed among them. After verifying the validity and reliability of the measurement instrument using the fit estimation indices and Cronbach's alpha coefficient, the gathered data were subjected to path analysis using SPSS Software and the direct and indirect effect of each of the assumed factors on the sense of attachment to university was determined. The results of this study indicated that, amongst the factors influencing the artificial environment of the university, "the proper proportion of the spaces' dimension with the performance" as well as "the number of their users" have the highest effect on the university students' sense of attachment to the university. Moreover, paying attention to the color used in the spaces and the thermal comfort conditions in the building indirectly lead to the improvement of the quality of the university students' relationship with the academic environment via influencing the performance of the administrative staff and the university-students' interactions.


Background: A whole-person representation captures not only patient problems but also patient strengths. To better understand and inform practice of person-centered care and documentation using a whole-person representation, a critical review of literature was conducted of the current state of patient problems and strengths documentation in electronic health records.
Methods: The informatics model of Data, Information, Knowledge and Wisdom is employed to develop this critical review. Two scientific databases were used to conduct a systematic search: CINAHL and Ovid Medline with the following search terms: strength*, problem*, whole person, wellbeing or well-being, electronic health record*, personal health record*, EHR*, and PHR*. 602 articles were returned. All articles were screened through review of titles, abstracts, or full texts. 24 articles were selected for this review.
Results: Four themes have emerged from this critical review. They are individual or cross-institutional use of problem-oriented EHRs, extension of problem-based EHRs with other integration, patient-centered integration of the problem-oriented EHR build, and construction of a whole-person representation to include strengths in the EHR documentation. The vast majority of articles focus on problem-based diagnoses and practices. Early reports of strengths documentation were found using a standardized interface terminology and ontology, the Omaha System. Results of two studies demonstrated the feasibility of using the Omaha System for whole-person documentation to capture perception of both problems and strengths.
Conclusion: Clinical information in EHRs is typically structured by problem-based diagnoses; however, there is emerging documentation of formalized strengths attributes using the Omaha System, which may promote a holistic approach to clinical practice and documentation using a person-centered, strength-based ontology.


The genomes of land plants vary dramatically in size and chromosome number, and ongoing studies are clarifying the processes that shape their composition, structure and function. Polyploidy produces an entirely duplicated genome where the processes of nonfunctionalisation, subfunctionalisation and neofunctionalisation occur at individual loci or across entire genetic pathways, with both short- and long-term effects. Transposable elements mould and alter genomes via a wide array of direct and indirect mechanisms extending well beyond their capacity to move throughout genomes. Horizontal gene transfer affects genome evolution of a lineage by incorporating novel genetic material from a separate lineage. Alternative splicing results in the inclusion and exclusion of a gene's exons and introns in processed messenger ribonucleic acid, altering the amino acid sequence and increasing an organism's protein repertoire without altering gene number. The impacts of these processes on plant genome evolution are just beginning to emerge as nonmodel genomes are sequenced.

Key Concepts

Polyploidy, or whole-genome duplication, can result in immediate genomic and genetic variation.
Gene retention or loss following polyploidy may depend on gene function and expression levels.
Transposable elements can actively or passively alter genome composition and genetic networks via a variety of processes.
Horizontal gene transfer has been most commonly found in plant mitochondrial genomes, although more cases are being found in nuclear genomes.
Alternative splicing can provide multiple gene products from a single nucleotide sequence.
The conservation and evolutionary significance of alternative splicing patterns are just beginning to be elucidated in plants.
Genome size in plants varies from among the smallest eukaryotic genomes to the largest eukaryotic genomes yet determined.

Keywords:

polyploidy;
whole-genome duplication;
horizontal gene transfer;
transposable elements;
alternative splicing;
plant evolution;
genome size


After a review on the state of tokamak transport theory, the methodology to derive experimental results will be described. Examples of confinement in ohmic plasmas and the deterioration with additional heating will be given. Some examples of improved confinement modes will be discussed. Fluctuation measurements and correlation with characteristic dimensionless numbers should reveal the clue to the unexplained phenomena. Recent information on the existence of transport barriers related to the magnetic field topology can explain anomalies in electron transport.


We report a novel digital coherent receiver based on sampling the signal in the optical domain to overcome the speed limitations of electrical analog-to-digital converters. Digital coherent receivers with aggregate optical sampling rates of up to 112 GHz are realized experimentally. The performance of such receivers is investigated in transmission experiments. Transmission of 56 GBd quadrature phase-shift keying signals over 610-km standard single-mode fiber and coherent detection with electronic impairment mitigation is demonstrated. The employed electrical analog-to-digital converters have only 20 GHz bandwidth and a sampling rate of 50 GHz.


Education of young people with mental disability is a difficult and complex process, requiring certain amount of knowledge, abilities and experience. The process of educating young people with mental disability remains important and relevant issue. Independence is closely associated with the real participation in social life opportunities: daily -decision making, planning of further activities. Mentally disabled young people must both be prepared to independent and social life, and be able to satisfy basic personal needs (take care of their health, budget, household etc.) in order to become a full-fledged member of society. Research object: success criteria of development of independent living skills in young people with mental disability. Article objective - theoretically and empirically substantiate opportunities of learning and training independent living skills and success criteria for mentally disabled young people at Independent Living Homes. The aim is specified by tasks: 1) to reveal the process of learning and training independent living skills for young people with mental disability; 2) to reveal success criteria of learning and training independent living skills for mentally disabled young people at Independent Living Homes, referring to experiences of social workers. Research methods: theoretical – analysis of scientific literature and documents, comparison, conclusion and systematization; empirical – data collection by using semi-structured interview method; a method of content analysis was used for analysing the survey data. The study included 7 social workers currently working in X Independent Living Homes of Lithuania. The working experience with mentally disabled people ranged between 2,5 and 7 years for all survey participants. This study revealed that success criteria for young people with mental disability living independently in communities are an ability to live on their own and join the community's life, as well as satisfy their basic personal needs such as taking care of themselves, setting and achieving personal goals, maintaining the tidiness at home and having an ability to encourage other people to be more tidy too. The ability to maintain at labour market is an important success criteria for young people with mental disability as well. While educating independent living skills of mentally disabled young people it is crucial to enable them to get a personal assistant services and social housing. Personal assistants would be able to give more attention to one particular young person, get to know his or her environment, be a part of his or hers life and provide support and help if it is needed.


Among the most important activities for supermarket retailers is the creation and marketing of store brands, also known as private label brands. Given the increasing quality-equivalence between national brands and store brands, they have become direct competitors, and pricing decisions should take this into account. In most cases, national brands still possess some degree of pricing and market power over store brands. In this chapter, we defi ne three components of market power for national brands versus store brands: (1) price premium; (2) volume premium; and (3) margin premium. Our chapter proceeds along the following lines. First, we delineate the factors that are the most important drivers of the three components of premium. Second, we discuss managerial implications about key success factors in the pricing of national brands and store brands. A key contribution of this chapter is that we incorporate emerging insights from the marketing literature on the pricing and market power of national brands versus store brands. Finally, we conclude by offering important future research directions.


We simulate reconstructed -motoneurons (MNs) under physiological and morphological realistic parameters and compare the modeled reciprocal (REC) and recurrent (REN) inhibitory postsynaptic potentials (IPSPs) containing voltage-dependent channels on the dendrites with the IPSPs of a passive MN model. Three distribution functions of the voltage-dependent channels on the dendrites are applied: a step function (ST) with uniform spatial dispersion; an exponential decay (ED) function, with channels with high density located proximal to the soma; and an exponential rise (ER) with a higher density of channels located distally. The excitatory and REN inhibitory inputs are located as a gaussian function on the dendrites, while the REC inhibitory synapses are located proximal to the soma. Our simulations generate four key results. (1) The distribution pattern of the voltage-dependent channels does not affect the IPSP peak, its time integral (TI), or its rate of rise (RR). However, the IPSP peak decreased in the presence of the active dendrites, while the EPSP peak increased. (2) Proximally located IPSP conductance produces greater IPSP peak, RR, and TI. (3) Increased duration of the IPSP produces greater RR and moderately increased TI and has a small effect on the peak amplitude. (4) The IPSP of both REC and REN models is specific to each MN: its amplitude is proportional to the MNs' input resistance, RN; the increase of IPSP at the proximal location of the IPSP synapses is inversely related to RN; and the effect of the IPSP conductance duration is insensitive to RN.


The study purposes at examining the computer-assisted English language learning technology for undergraduate university students. Computer-Assisted English Language Learning (CAELL) is an emerging trend that has highly impacted traditional theories of learning and teaching foreign languages. This new trend has introduced innovative techniques and the latest pedagogies for teachers and students of all levels. This is an attempt to look at teaching and learning practices through CAELL. The study is conducted in the mixed method in which sequential exploratory design is employed. A random sampling technique is used to select the population for this research. Data is collected from both teachers and students. 10 English language teachers are requested for semi-structured interviews to explore the CAELL teaching practices. Furthermore, a questionnaire is adapted for 146 undergraduate students of Shaheed Benazir Bhutto University (SBBU) Shaheed Benazirabad and its campuses. Qualitative data is thematically analyzed and Statistical Package for Social Sciences software (SPSS) 20th version is used to analyzed quantitative data. The findings indicate that there is a positive effect of CAELL technology among university students and teachers. Among four skills of language, students effectively improve their listening skills by using CAELL. This new trend increases students' motivation and eases them to learn English without pen and paper. Students prefer to use CAELL but most of the participants are unaware of using CAELL because of lack of facilities. Teachers are of the view that effective English language teaching demands CAELL knowledge. Last but not least limitations and delimitations are identified and areas for further studies are recommended.


A new scan that matches an aided Inertial Navigation System (INS) with a low-cost LiDAR is proposed as an alternative to GNSS-based navigation systems in GNSS-degraded or -denied environments such as indoor areas, dense forests, or urban canyons. In these areas, INS-based Dead Reckoning (DR) and Simultaneous Localization and Mapping (SLAM) technologies are normally used to estimate positions as separate tools. However, there are critical implementation problems with each standalone system. The drift errors of velocity, position, and heading angles in an INS will accumulate over time, and on-line calibration is a must for sustaining positioning accuracy. SLAM performance is poor in featureless environments where the matching errors can significantly increase. Each standalone positioning method cannot offer a sustainable navigation solution with acceptable accuracy. This paper integrates two complementary technologies—INS and LiDAR SLAM—into one navigation frame with a loosely coupled Extended Kalman Filter (EKF) to use the advantages and overcome the drawbacks of each system to establish a stable long-term navigation process. Static and dynamic field tests were carried out with a self-developed Unmanned Ground Vehicle (UGV) platform—NAVIS. The results prove that the proposed approach can provide positioning accuracy at the centimetre level for long-term operations, even in a featureless indoor environment.


Current approaches to the regulation of coal mining activities in Australia have facilitated the extraction of substantial amounts of coal and coal seam gas. The regulation of coal mining activities must now achieve the reduction or mitigation of greenhouse gas emissions in order to address the challenge of climate change and achieve ecologically sustainable development. Several legislative mechanisms currently exist which appear to offer the means to bring about the reduction or mitigation of greenhouse gas emissions from coal mining activities, yet Australia's emissions from coal mining continue to rise. This article critiques these existing legislative mechanisms and presents recommendations for reform.


The Search for Extraterrestrial Intelligence (SETI) makes certain assumptions which guide all current search programs. To illustrate some, this includes (1) that interstellar flight is not possible (2) that the motivations of interstellar cultures are based largely on anthropomorphic understandings of homo sapiens (3) that the Fermi Paradox and the Drake equation are the starting point (axioms) of all reasoning (4) that definitions of 'life' are based largely on our understanding of homeostasis (5) that radio waves are the most likely method of interstellar communications (6) that unknown single event source signatures detected in space are not amenable to scrutiny due to the demands of the scientific method to be reproducible (7) that such anomalous signatures are either astronomical or communications based in type with no consideration for emissions from advanced industrialisation or propulsion and power technology. These assumptions, and others, have guided the SETI community towards a constrained level of thinking that is equivalent to philosophical dogma. In this paper, we unpack these assumptions, and others, and argue that the potential for life and intelligent life in the Cosmos may be much greater than the SETI community currently appears to conclude. It is also argued that more progress in our underanding of our place in the Cosmos can be made, if the separate disciplines of astronomy, interstellar spacecraft design, SETI, biology and philosophy can work together in a complementary way. Presented at the 47th IAA Symposium on the Search for Extraterrestrial Intelligence. SETI and Society.


Background Despite reported early successes, anterior cruciate ligament (ACL) injury rates have not diminished. Currently explicit learning strategies are mainly used for prevention. However, this may be unsuitable for the control of complex motor skills. Objective The purpose was to investigate explicit and implicit learning while keeping balance on a 4 mm narrow ridge. Results can contribute to the development of ACL injury prevention programs. Design Randomised controlled trial. Setting Laboratory based study with recreational athletes. Participants 60 healthy subjects between 18 and 24 years were recruited from the university population. Females (n=36) and males (n=24) were equally distributed over three groups; implicit learning, explicit learning and the control group. Interventions Balance time on the ridge was investigated where the groups received different types of feedback after each trial; implicit (visual feedback from video of the best trial so far), explicit (instructions) and no feedback. During the retention test after 2 weeks none of the subjects received any feedback. All subjects conducted 25 trials during both measurements. The independent t-test was used in SPSS 16.0 (SPSS Inc., Chicago, IL) where the alpha level was set a priori at p<0.05. Main outcome Measures Grow of balance time (based on first grade regression line). Results Growth during the intervention for implicit, explicit and control was 2.36 (SD ± 3.21; p=0.009), 1.53 (SD ± 2.09; p=0.001) and 0.84 (SD ± 1.26; p=0.209) respectively. Growth of the implicit group was significantly different from the control group (p=0.03). No other significant differences were found. Growth and group differences were not significant from each other during the retention test (p>0.05). Conclusion Before use in the clinical setting, future research is needed to evaluate and improve the learning strategies. SD were high, which could explain the results.


In this work we address the problem of point-cloud denoising where we assume that a given point-cloud comprises (noisy) points that were sampled from an underlying surface that is to be denoised. We phrase the point-cloud denoising problem in terms of a dictionary learning framework. To this end, for a given point-cloud we (robustly) extract planar patches covering the entire point-cloud, where each patch contains a (noisy) description of the local structure of the underlying surface. Based on the general assumption that many of the local patches (in the noise-free point-cloud) contain redundant information (e.g. due to smoothness of the surface, or due to repetitive structures), we find a low-dimensional affine subspace that (approximately) explains the extracted (noisy) patches. Computationally, this is achieved by solving a structured low-rank matrix factorization problem, where we impose smoothness on the patch dictionary and sparsity on the coefficients. We experimentally demonstrate that our method outperforms existing denoising approaches in various noise scenarios.


This study is concerned with the improvement of school uniforms in Zimbabwe by taking into account the wishes of pupils and by involving them in their production. A case study focusing on urban schools and district council schools was conducted. The study was undertaken in the belief that if students are involved in the design and making of uniforms, these will be functional, and pupils are likely to appreciate them.
The study revealed three interesting points:
1. Pupils were generally dissatisfied with the function of uniforms
2. The majority of the pupils expressed their willingness to be involved in the making of uniforms because they believed it helped reduce the cost of buying the uniforms, and they would produce uniform garments whose functional values would be close to their tastes.
3. Teachers expressed their willingness to help the pupils with the making of some uniform garments as part of education with production (EWP).
Based on that the above findings, a strong case can be made that favors the involvement of pupils in the making of uniforms and, to that extent, the concept of education with production will become more meaningful to them. Furthermore, by participating in the making of their own uniforms, pupils will gain practical skills in designing and constructing garments


For years economists have urged policymakers to use market-based approaches such as cap-and-trade programs or emission taxes to control pollution. The SO2 allowance market created by Title IV of the 1990 U.S. Clean Air Act Amendments represents the first real test of the wisdom of economists' advice. Subsequent urban and regional applications of NOx emission allowance trading took shape in the 1990s in the United States, culminating in a second large experiment in emission trading in the eastern United States that began in 2003. This paper provides an overview of the economic rationale for emission trading and a description of the major U.S. programs for sulfur dioxide (SO2) and nitrogen oxides (NOx). We evaluate these programs along measures of performance including cost savings, environmental integrity, and incentives for technological innovation. We offer lessons for the design of future programs including, most importantly, those reducing carbon dioxide.


Falls are the leading cause of fatal and non-fatal injuries among seniors worldwide, with serious and costly consequences. Compensatory balance responses (CBRs) are reactions to recover stability following a loss of balance, potentially resulting in a fall if sufficient recovery mechanisms are not activated. While performance of CBRs are demonstrated risk factors for falls in seniors, the frequency, type, and underlying cause of these incidents occurring in everyday life have not been well investigated. This study was spawned from the lack of research on development of fall risk assessment methods that can be used for continuous and long-term mobility monitoring of the geriatric population, during activities of daily living, and in their dwellings. Wearable sensor systems (WSS) offer a promising approach for continuous real-time detection of gait and balance behavior to assess the risk of falling during activities of daily living. To detect CBRs, we record movement signals (e.g. acceleration) and activity patterns of four muscles involving in maintaining balance using wearable inertial measurement units (IMUs) and surface electromyography (sEMG) sensors. To develop more robust detection methods, we investigate machine learning approaches (e.g., support vector machines, neural networks) and successfully detect lateral CBRs, during normal gait with accuracies of 92.4% and 98.1% using sEMG and IMU signals, respectively. Moreover, to detect environmental fall-related hazards that are associated with CBRs, and affect balance control behavior of seniors, we employ an egocentric mobile vision system mounted on participants chest. Two algorithms (e.g. Gabor Barcodes and Convolutional Neural Networks) are developed. Our vision-based method detects 17 different classes of environmental risk factors (e.g., stairs, ramps, curbs) with 88.5% accuracy. To the best of the authors knowledge, this study is the first to develop and evaluate an automated vision-based method for fall hazard detection.


Background: The time to first cigarette (TTFC) is a good indicator of several dimensions of nicotine dependence. An early TTFC is also associated with increased lung and oral cancer risk. Our objective was to determine the relationship between TTFC and exposure to tobacco smoke carcinogens. Methods: We conducted a cross-sectional analysis of a nationally representative subsample of smoking adults that had urinary samples analyzed for tobacco biomarkers. The study included 1,945 participants from the 2007–2008 and 2009–2010 National Health and Nutrition and Examination Survey. The main outcome measure was creatinine-adjusted urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Results: The cigarette-per-day adjusted levels of NNAL were twice as high in participants who smoked within 5 minutes after waking than in participants who refrained from smoking for at least 1 hour (0.58 vs. 0.28 ng/mL, P < 0.001). In multivariate linear models, a shorter TTFC was significantly associated with increasing NNAL levels, after adjusting for cigarettes smoked per day (or cotinine), secondhand smoke exposure, age, sex, race/ethnicity, and other potential confounders. Conclusions: These data show that in a nationally representative sample, there is a dose-dependent relationship between earlier smoking in the day and higher biologic exposure to a tobacco smoke carcinogen. Impact: Our study provides further evidence that highlights the relationship between TTFC, nicotine dependence, and cancer risk. Cancer Epidemiol Biomarkers Prev; 22(4); 615–22. ©2013 AACR.


A recent trend in spoken dialogue research is the use of reinforcement learning to train dialogue systems in a simulated environment. Past researchers have shown that the types of errors that are simulated can have a significant effect on simulated dialogue performance. Since modern systems typically receive an N-best list of possible user utterances, it is important to be able to simulate a full N-best list of hypotheses. This paper presents a new method for simulating such errors based on logistic regression, as well as a new method for simulating the structure of N-best lists of semantics and their probabilities, based on the Dirichlet distribution. Off-line evaluations show that the new Dirichlet model results in a much closer match to the receiver operating characteristics (ROC) of the live data. Experiments also show that the logistic model gives confusions that are closer to the type of confusions observed in live situations. The hope is that these new error models will be able to improve the resulting performance of trained dialogue systems.


Understanding the characteristics of water use efficiency (WUE) could enhance our understanding of the integrated response of terrestrial ecosystems to climate change. In this study, the vegetation photosynthesis model (VPM) and the revised remote sensing-Penman Monteith (RRS-PM) model were used to characterize the spatial-temporal dynamics of gross primary productivity (GPP) and evapotranspiration (ET) in the Yangtze River Delta (YRD) region. Our predicted GPP and ET results were in the range of those reported by other models. To be specific, the RRS-PM model could explain 85% of the variability in ET at the Anji site, China. The root mean square error between the simulation value and the measured ET was 8.543 mm month -1 . For the evergreen broadleaf forest, deciduous needle leaf forest and deciduous broadleaf forest, GPP decreased and ET increased, thus the WUE = (GPP/ET) inevitably decreased. The increase in WUE in grassland was due to the decreased ET, for which the rate of decrease was greater than for GPP. For the spatial distribution of WUE, the maximum value occurred in the southern and northeastern parts of the YRD region, while the minimum value was distributed in the middle and northwest. This is likely due to the different land-cover types. In the south, there is more forest, while in the north the land-cover type is almost entirely cropland. In our study, GPP increased with increasing LAI across all of the plant function types. (ET), photosynthesis


Single-molecule fluorescence resonance energy transfer (smFRET) methods were used to study the assembly pathway and DNA unwinding activity of the bacteriophage T4 helicase-primase (primosome) complex. The helicase substrates used were surface-immobilized model DNA replication forks "internally" labeled in the duplex region with opposed donor/acceptor (iCy3/iCy5) chromophore pairs in the lagging and leading strands. The time dependence of the smFRET signals was monitored during the unwinding process, and helicase rates and processivities were measured as a function of GTP concentration. This smFRET approach was also used to investigate the subunit stoichiometry of the primosome and the assembly pathway required to form functional and fully active primosome-DNA complexes. We confirmed that gp41 helicase monomer subunits form stable hexameric helicases in the presence of GTP and that the resulting (gp41)(6) complexes bind only weakly at DNA fork junctions. The addition of a single subunit of gp61 primase stabilized the resulting primosome complex at the fork and resulted in fully active and processive primosome helicases with gp41:gp61 subunit ratios of 6:1, while higher and lower subunit ratios substantially reduced the primosome unwinding activity. The use of alternative assembly pathways resulted in a loss of helicase activity and the formation of metastable DNA-protein aggregates, which were easily detected in our smFRET experiments as intense light-scattering foci. These single-molecule experiments provide a detailed real-time visualization of the assembly pathway and duplex DNA unwinding activity of the T4 primosome and are consistent with more indirect equilibrium and steady state results obtained in bulk solution studies.


Carter, B., & McGoldrick, M. (1999). The Expanded Family Life Cycle: Individual, Family, and Social Perspectives (3rd ed.). Needham Heights, MA: Allyn & Bacon. 541 pages. ISBN 0-205-20009-5. Price: $73. The third edition of Carter and McGoldrick (Eds.), The Expanded Family Life Cycle, is a valuable resource for family therapists, students of family therapy and family science, as well as a range of professionals working with and advocating for families. Although family therapy terminology is interspersed throughout the book and the final four chapters are written directly to clinicians, the content of the book and the message of recognition and appreciation for diversity are appropriate for a variety of audiences. The book is divided into three parts encompassing 30 chapters written by respected scholars and clinicians in the family therapy field. An expanded definition of family is applied throughout the book with considerable attention paid to diversity in culture and family structure. A multisystem approach is used to examine the family, beginning with individual, immediate, and extended family interactions and expanding to include the influence of community, culture, and society. Within the context of the life cycle framework, the primary goal of the book is to acknowledge the many systemic forces that influence individual and family development over time. Consequently issues of race, gender, class, culture, sexual orientation, ethnicity, spirituality, and religiosity are repeatedly recognized for their impact on development. The first section of the book, "Conceptual Perspectives," contains 12 chapters that address a range of social issues and their influence on the individual and family system. Chapter 1, authored by the editors, introduces a broader definition of family and emphasizes the conceptual flexibility of the family life cycle framework when applied to diverse family structures. The authors recognize vertical and horizontal family stressors, intergenerational structures, and the importance of sociohistorical context. The passions of Carter and McGoldrick are apparent in their writing and in their strong political statements. They encourage practitioners to go beyond addressing immediate client problems and recognize the larger social context in which their clients live. Family therapists (and other family professionals) are encouraged to raise issues of racism, classism, sexism, and other discriminatory attitudes and to empower themselves and their clients to initiate social change. The remaining chapters in this section address the influence of ethnic culture, class, gender, history, ordinal position, death, migration, and family rituals on family functioning over time. Chapter 3 illustrates how genograms can be used as a therapeutic tool. The chapter consists of a detailed examination of Sigmund Freud's family history using a Freud family genogram. Finally, it was refreshing to see entire chapters dedicated to the effect of culture on family life (chap. 4), men's issues (chap. 7), and sibling relationships (chap. 9). The second section of the book, "Perspectives on the Evolving American Family," encompasses developmental issues of young adulthood, intimate relationships, parenthood, and aging within the context of the family life cycle. This section celebrates family diversity by providing chapters about the unique challenges and strengths of midlife families, single-parent families, gay and lesbian families, reconstituted families, as well as families living in poverty and experiencing divorce. …


As Excel applications become more complex and the Windows development platform more powerful, Excel developers need books like this to help them evolve their solutions to the next level of sophistication. Professional Excel Development is a book for developers who want to build powerful, state-of-the-art Excel applications using the latest Microsoft technologies. Gabhan Berry, Program Manager, Excel Programmability, Microsoft The first edition of Professional Excel Development is my most-consulted and most-recommended book on Office development. The second edition expands both the depth and range. It shines because it takes every issue one step further than you expect. The book relies on the authors current, real-world experience to cover not only how a feature works, but also the practical implications of using it in professional work. Shauna Kelly, Director, Thendara Green This book illustrates techniques that will result in well-designed, robust, and maintainable Excel-based applications. The authors advice comes from decades of solid experience of designing and building applications. The practicality of the methods is well illustrated by the example timesheet application that is developed step-by-step through the book. Every serious Excel developer should read this and learn from it. I did. Bill Manville, Application Developer, Bill Manville Associates The Start-to-Finish Guide to Building State-of-the-Art Solutions with Excel 2007 In this book, four world-class Microsoft Excel developers offer start-to-finish guidance for building powerful, robust, and secure applications with Excel. The authorsthree of whom have been honored by Microsoft as Excel Most Valuable Professionals (MVPs)show how to consistently make the right design decisions and make the most of Excels most powerful new features. Using their techniques,you can reduce development costs, time to market, and hassleand build more effective, successful solutions. Fully updated for Excel 2007, this book starts where other books on Excel programming leave off. Through a hands-on case study project, youll discover best practices for planning, architecting, and building Excel applications that are robust, secure, easy to maintain, and highly usable. If youre a working developer, no other book on Excel programming offers you this much depth, insight, or value. Design worksheets that will be more useful and reliable Leverage built-in and application-specific add-ins Construct applications that behave like independent Windows programs Make the most of the new Ribbon user interface Create cross-version applications that work with legacy versions of Excel Utilize XML within Excel applications Understand and use Windows API calls Master VBA error handling, debugging, and performance optimization Develop applications based on data stored in Access, SQL Server, and other databases Build powerful visualization solutions with Excel charting engine Learn how to work with VB.NET and leverage its IDE Automate Microsoft Excel with VB.NET Create managed COM add-ins for Microsoft Excel with VB.NET Develop Excel solutions with Visual Studio Tools for Office (VSTO) Integrate Excel with Web Services Deploy applications more securely and efficiently


During the past decade, innovative digital technology and Internet marketplaces have created a variety of 'phenomena' of businesses, media and institutions considered to be important interaction channels in the music industry, along with an influx of Peer-to-Peer services such as Napster, and Kazaa shifting the business models of major music labels and distributors. Considering the Australian Music Association reported an annual retail turnover of approximately $300 million in 1992 and later in 1999, an increase in figures reported at $396.8 million with the inclusion of music DVD sales, the notion of value-adding to a music product emerges as a profitable venture at each length of the music industry's value chain. In spite of this, Australian studies have often overlooked the underlying perceptions, fears and ideas of those working within the value chain, especially regarding the impact of new technology on their roles. This paper identifies the perceptions of various intermediaries within the Australian Music Industry, identifying common themes and viewpoints amongst the study's participants. Consequently, the paper concluded that the perception of value in the music industry is somewhat influenced by a variety of factors, including music knowledge, communication and dependence on intermediaries to name a few. Common themes were revealed throughout the study include the perception of competitive advantage, new opportunities from new technology and the notion of defining a gimmick versus Value-Adding emerged as indicative of adding value from the study participants.


Bit patterned media recording (BPMR) is a candidate technology proposed to extend the areal density growth capability of magnetic recording systems. In conventional granular magnetic recording (CGMR), bits of information are recorded onto a number of randomly distributed magnetic grains. The difficulty for the granular media approach is that due to the randomness of the grains, a certain minimum number of grains are required in order to maintain the media signal to noise ratio (SNR). This requires smaller grains as the bits are shrunk and we end up with either unstable, or unwriteable grains as per the well-known media-trilemma. In BPMR, instead of random positions, the "grains'' are ordered into a well-defined lattice of magnetic islands. Because of this ordering, the media SNR is no longer determined by the number of grains per bit as in CGMR, but is defined by the geometrical and magnetic distributions of the fabrication process of the media. Analytical models exist for BPMR, that flip grains in the media based on the switching field distribution (SFD) and the knowledge of the applied head field. On the other side, a statistical model for CGMR has been proposed that measures probabilities of grains flipping based on micromagnetic simulations, named the grain flipping probability (GFP) model. In this work, we adapt the GFP model for BPMR and perform a comparison between densities predicted via the analytical and GFP models, by processing the signals from these models with the appropriate detectors and LDPC (low density parity check) decoders.


INTRODUCTION
Staphylococcus aureus is the etiological agent for a wide range of human infections, and its pathogenicity largely depends on various virulence factors associated with adherence, evasion of the immune system and damage of the host. This study determined the prevalence of methicillin-resistant S. aureus (MRSA) and some selected virulence genes in clinical isolates of S. aureus from South-Western Nigeria.

MATERIALS AND METHODS
The antibiotic susceptibility of 156 S. aureus isolates to various antibiotics was determined. Moreover, polymerase chain reaction detection of the mecA gene was performed including SCCmec typing, and the isolates were screened for selected genes (alpha hemolysin [hla], intracellular adhesion A [icaA], Panton-Valentine leukocidin [PVL], fibronectin binding protein A [fnbA], bone sialoprotein binding protein [bbp], exfoliative toxin A [eta], exfoliative toxin B [etb], and collagen binding adhesion [cna]) associated with virulence.

RESULTS
The prevalence of mecA gene was 42.3% (66 out of 156 S. aureus), and SCCmec typing showed that 24 (36.4%) carried the SCCmec II element, 4 (6.1%) with type III, 10 (15.2%) with SCCmec IV, and 28 (42.4%) harbored type V. The proportion of S. aureus with the following genes was ascertained: Hla (55.1%), icaA (42.3%), PVL (34.6%), fnbA (8.3%), bbp (4.5%), and eta (3.8%). All the isolates were etb and cna negative. The prevalence of the PVL gene in methicillin susceptible Staphylococcus aureus (MSSA) was 53.3% compared with 9.1% of MRSA. An association between virulence genes (eta and icaA) and mecA positive S. aureus; and significant difference in the distribution of virulence genes in in-patients and out-patients were found. The MRSA strains in South-Western Nigeria were dominated by SCCmec II and SCCmec V.

CONCLUSION
The study concluded that there is a high prevalence of MRSA in Nigeria with association of eta and icaA genes with mecA gene in S. aureus isolates.


This chapter developed from a paper delivered to the Visual Delights conference at the University of Sheffield in 2002,
concentrating on film exhibition in Brighton and Hove in 1896-97 and, as such, represents the initial stages of research for an
early film exhibition history of Brighton and Hove that Gray was to curate (output 1). This wider history begins with the arrival of the
Kinetoscope in 1895 and concludes with the opening of the first purpose-built cinemas in 1909-10. It is shaped by the need to
conceptualise the dynamic and holistic relationship between production and exhibition within film culture as it evolved within one
particular place.
Gray's research recognises the fact that the history of film exhibition in Britain before the First World War had not previously
been systematically chronicled and analysed. In 2006 at the Ninth International Domitor Conference, held at the University of Michigan, Gray presented a paper on film exhibition in Brighton from 1897 to 1900, focusing on the rise of patriotic multi-media entertainments that combined film with lantern slides, music, song and narration. It will be published as part of the conference proceedings in either 2007 or 2008. Domitor is the international early cinema society. The triennial Visual Delights conference is allied to Early Popular Visual Culture (Routledge), the peer-reviewed journal dedicated to popular visual culture before 1930.
Gray is one of the journal's associate editors.


The purpose of the paper was to determine whether changes in the learning process could be assessed based on characteristic ERP and ERP changes, as well as the level of model accuracy that is required to ascertain the changes in the learning process. We presented arithmetic tasks to subjects and simultaneously recorded correct response rate, response time, and electroencephalogram (EEG). Then Event Related Potential (ERP) was calculated from the EEG. Three-step modeling was then conducted using correct response rate and response time as objective variables and characteristic ERP as an explanatory variable. These results were interpreted using the learning process model.


0.5% and 1.0% (w/w) of boric acid (H3BO3) were incorporated in rubberwood (Hevea brasiliensis) particleboards
either by initially mixing the boric acid powder with urea formaldehyde adhesive or spraying boric acid solution
onto the furnish during blending. Two types of urea formaldehyde, i.e. E1-glue (maximum permissible
formaldehyde emmision < 0.1 ppm) and E2-glue (maximum permissible formaldehyde emmision 0.1-1.0 ppm)
were used as the bonding agent. The targeted density of the boards was 650 kg/m3
. The board properties and
durability against white rot fungus were evaluated in accordance with JIS A 5908-1983 and ASTM D2017-71,
respectively. The chemical loading in the board was in the range of 0.42-0.47% and 0.64-0.70%, respectively
when 0.5% and 1.0% of boric acid (based on the dry-weight of the particles) were incorporated in the boards.
The dry modulus of rupture (MaR), dry modulus of elasticity (MOE) of the boric acid-treated boards were
significantly reduced. The reduction of the properties increased as the chemical loading in the treated boards increases. However, wet MOR and wet MOE, internal bonds (IB) and thickness swelling (TS) of treated boards
at both concentration levels did not differ significantly compared to the untreated boards. Particleboards bonded
with E2-glue were more resistant to white rot Jungus (Pycnoporous sanguineus) than those bonded with El-glue.
The presence of boric acid significantly increased the durability of board against white rot Fungus, and the
resistance towards the Fungus increased as the boric acid loading increases.


The purpose of the study was to explore the effects that individual vs. collective structured creative musical problem solving tasks had on students' compositional products. Subjects in a convenience sample of 32 fourth-graders and 32 fifth-graders were randomly assigned to either the individual or collective condition. The 3 treatment sessions were characterized by an open-ended creative problem solving task, which included questions intended to guide subjects through 3 stages of the creative problem solving process: Understanding the Problem, Generating Ideas, and Planning for Action. Subjects participated in the pre- and posttest individually. Three experienced music educators assessed the compositional products in terms of pattern use, cohesiveness, and creativity. The originally intended MANCOVAs could not be carried out because the data did not meet the necessary assumptions. Pretest and posttest scores were explored with individual ANOVAs. The Bonferroni technique was used to adjust the alpha level. The statistical analyses showed that subjects exposed to the individual condition obtained higher scores than subjects exposed to the collective condition on six of the eight explored subtests, but these differences were not significant. The level of interjudge reliability decreased at each of the three measurements of the study: pilot test, pretest, and posttest. The study's results suggest that music educators interested in observing specific characteristics of individual students' compositional products, such as the levels of cohesiveness, creativity, and pattern use, could do so regardless of the condition under which students were exposed to compositional tasks, either individually or collectively. Recommendations for future research include the use of a measurement instrument specifically designed for open-ended tasks, and the exploration of the current study's measurement instrument with closed-ended tasks. The study highlights the need for appropriate measurement instruments designed for the compositional tasks at hand, and the need for research results reported clearly, so that more advancement of this field is possible.


BACKGROUND
Immune checkpoint inhibitors provide significant clinical benefit to a subset of patients, but novel prognostic markers are needed to predict which patients will respond. This study was initiated to determine if features of patient T cell repertoires could provide insights into the mechanisms of immunotherapy, while also predicting outcomes.

METHODS
We examined T cell receptor (TCR) repertoires in peripheral blood of 25 metastatic pancreatic cancer patients treated with ipilimumab with or without GVAX (a pancreatic cancer vaccine), as well as peripheral blood and tumor biopsies from 32 patients treated with GVAX and mesothelin-expressing Listeria monocytogenes with or without nivolumab. Statistics from these repertoires were then tested for their association with clinical response and treatment group.

RESULTS
We demonstrate that, first, the majority of patients receiving these treatments experience a net diversification of their peripheral TCR repertoires. Second, patients receiving ipilimumab experienced larger changes in their repertoires, especially in combination with GVAX. Finally, both a low baseline clonality and a high number of expanded clones following treatment were associated with significantly longer survival in patients who received ipilimumab but not in patients receiving nivolumab.

CONCLUSIONS
We show that these therapies have measurably different effects on the peripheral repertoire, consistent with their mechanisms of action, and demonstrate the potential for TCR repertoire profiling to serve as a biomarker of clinical response in pancreatic cancer patients receiving immunotherapy. In addition, our results suggest testing sequential administration of anti-CTLA-4 and anti-PD-1 antibodies to achieve optimal therapeutic benefit.

TRIAL REGISTRATION
Samples used in this study were collected from the NCT00836407 and NCT02243371 clinical trials.

FUNDING
Research supported by a Stand Up To Cancer Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research grant (SU2C-AACR-DT14-14). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research (AACR). Additional clinical trial funding was provided by AACR-Pancreatic Cancer Action Network Research Acceleration Network grant (14-90-25-LE), NCI SPORE in GI Cancer (CA062924), Quick-Trials for Novel Cancer Therapies: Exploratory Grants (R21CA126058-01A2), and the US Food and Drug Administration (R01FD004819). Research collaboration and financial support were provided by Adaptive Biotechnologies.


Systematic examination of published sedimentary and metamorphosed pelite analyses has revealed evidence of significant mass transfer and volume strain during regional metamorphism. Statistical analysis of the data shows that Barrovian zone metamorphism of pelitic schist generally causes increases in the whole-rock concentrations of the low-solubility elements Ti and All The observed increases in Ti and Al contents as functions of metamorphic grade are almost certainly due to residual enrichment caused by the removal of other more soluble species. Application of mass-balance principles to the petite compositional trends indicates that the average pelite may lose as much as 30% of its mass and volume during progressive metamorphism from subgreenschist to amphibolite facies conditions. The bulk of the lost mass is silica, not volatiles. In addition, other elements, particularly Ca, Na, and K, appear to be highly mobile in deep-crustal metamorphism. Contrary to conventional interpretations, it is concluded that the regional metamorphism of pelites is not an isochemical process.


MOTIVATION
Biological networks are often modeled by random graphs. A better modeling vehicle is a multigraph where each pair of nodes is connected by a Poisson number of edges. In the current model, the mean number of edges equals the product of two propensities, one for each node. In this context it is possible to construct a simple and effective algorithm for rapid maximum likelihood estimation of all propensities. Given estimated propensities, it is then possible to test statistically for functionally connected nodes that show an excess of observed edges over expected edges. The model extends readily to directed multigraphs. Here, propensities are replaced by outgoing and incoming propensities.

RESULTS
The theory is applied to real data on neuronal connections, interacting genes in radiation hybrids, interacting proteins in a literature curated database, and letter and word pairs in seven Shaskespearean plays.

AVAILABILITY
All data used are fully available online from their respective sites. Source code and software is available from http://code.google.com/p/poisson-multigraph/.


Part 28 includes a supplement purported to combat fatigue and enhance growth hormone (ornithine); a well-known ingredient (phenylalanine) of a well-known sweetener (aspartame); a possible energy enhancer via 2,3 diphosphoglycerate (phosphate); and a rather dubious supplement purported in the early 1940s to have a wide range of medicinal effects (pangamic acid). Of these, only phosphate appears to have some credible evidence to support the claims of an ergogenic effect.

### K Currell

Ornithine is an amino acid which plays a key role in the urea cycle, facilitating the disposal of ammonia. Ammonia is produced during intense exercise and may be one of the causes of fatigue. There is some evidence that L-ornithine hydrochloride supplementation prior to high-intensity exercise may prevent fatigue and improve performance by modulating the metabolism of ammonia.1 At present, the evidence is far from conclusive with a need to conduct more research using valid measures of performance.

It has been suggested that ornithine supplementation will promote the secretion of growth hormone within humans.2 However, research has not been conducted to show whether this may enhance the adaptation to training and ultimately lead to an improvement in the performance.

One potential avenue of future research is ornithine-α-ketoglutarate. This has been shown to improve the recovery of individuals from burns, trauma and in the postoperative state. It may also be a precursor of nitric oxide.2 At present, there is not enough evidence to support the use of ornithine in sport performance. However, further research should be conducted to investigate its use.

### DR Moore

Phenylalanine is …


BEKTAS, Z. K., B. MIRAN, O. K. UYSAL and C. GUNDEN, 2011. Consumer awareness for food safety in Turkey. Bulg. J. Agric. Sci., 17: 470-483 The main objective of this study is to determine the level of consumer awareness about food safety in Izmir, one of the biggest provinces in Turkey. The data is obtained from a survey of 385 consumers in Izmir, between April-2004 and February-2005. According to probit models, high income and education as well as the presence of elderly individuals in the house increase the probability of having knowledge on food safety. Likewise, probability of married consumers with knowledge about food safety and high level of education, of being affected by food scandals is high. It is concluded that, increased awareness of food safety pass through informative campaigns targeting especially lowand middle-income groups and masses with low education levels, and through endeavours of improving the levels of education and welfare.


Abstract Since its formal establishment in 1996, the European Society for the History of Economic Thought (ESHET) has organised 23 annual conferences. Participation data gathered from various sources reveals 1777 unique participants. In order to study their regular engagement with ESHET, we focus only on a group of 476 scholars who attended at least three conferences. We collect available biographic data on this smaller group of regular attendees and analyse their educational background, career trajectories, geographical and gender representation. With this prosopography we depict the evolving structure of the history of economic thought community in Europe and beyond.


A continuous Quaternary sediment sequence was recovered from Hole 902-C9001C during the D/V Chikyu 2006 mission along the northeastern margin of Japan. The age and rate of deposition of this core were estimated using calcareous nannofossil biostratigraphy and oxygen isotope curves measured from benthic foraminifera (Uvigerina akitaensis) and dated from 740 ka to the present, a period that spanned the Brunhes normal polarity epoch. Sediment consisted of diatomaceous siltstone and contained an abundance of radiolarians. A total of 91 radiolarian species was found in the core, of which 74 were analysed. Of these radiolarian species, 36 demonstrated continuous stratigraphical distribution over the past 740 ka and 38 had shorter ranges of biostratigraphical interest. Three of the 38 species were determined to be novel and are described in the present study (Amphisphaera tanzhiyuani sp. nov., Schizodiscus japonicus sp. nov. and Siphonosphaera? paraphoros sp. nov.). Based on 17 radiolarian bioevents, including four datums which have been commonly used across a wide area of the North Pacific, the radiolarian sequence of this core was divided into 8 zones: Amphirhopalum virchowii Zone (613–740 ka), Spongaster tetras irregularis Zone (516–613 ka), Cyrtidosphaera reticulata Zone (357–516 ka), Spongurus cylindricus Zone (238–357 ka), Pterocanium depressum Zone (209–238 ka), Spongoliva ellipsoides Zone (131–209 ka), Ceratospyris problematica Zone (33–131 ka), and the Acanthodesmia vinculata Zone (0–33 ka).


We present an algorithm that generates natural and intuitive deformations via direct manipulation for a wide range of shape representations and editing scenarios. Our method builds a space deformation represented by a collection of affine transformations organized in a graph structure. One transformation is associated with each graph node and applies a deformation to the nearby space. Positional constraints are specified on the points of an embedded object. As the user manipulates the constraints, a nonlinear minimization problem is solved to find optimal values for the affine transformations. Feature preservation is encoded directly in the objective function by measuring the deviation of each transformation from a true rotation. This algorithm addresses the problem of "embedded deformation" since it deforms space through direct manipulation of objects embedded within it, while preserving the embedded objects' features. We demonstrate our method by editing meshes, polygon soups, mesh animations, and animated particle systems.


The acquisition of a scene-specific normal behaviour model underlies many existing approaches to the problem of automated video surveillance. Since it is unrealistic to acquire a comprehensive set of labelled behaviours for every surveyed scenario, modelling normal behaviour typically corresponds to modelling the distribution of a large collection of unlabelled examples. In general, however, it would be desirable to be able to filter an unlabelled dataset to remove potentially anomalous examples. This thesis proposes a simple semi-supervised learning framework that could allow a human operator to efficiently filter the examples used to construct a normal behaviour model by providing occasional feedback: Specifically, the classification output of the model under construction is used to filter the incoming sequence of unlabelled examples so that human approval is requested before incorporating any example classified as anomalous, while all other examples are automatically used for training. A key component of the proposed framework is an incremental one-class learning algorithm which can be trained on a sequence of normal examples while allowing new examples to be classified at any stage during training. The proposed algorithm represents an initial set of training examples with a kernel density estimate, before using merging operations to incrementally construct a Gaussian mixture model while minimising an information-theoretic cost function. This algorithm is shown to outperform an existing state-of-the-art approach without requiring off-line model selection. Throughout this thesis behaviours are considered in terms of whole motion trajectories: in order to apply the proposed algorithm, trajectories must be encoded with fixed length vectors. To determine an appropriate encoding strategy, an empirical comparison is conducted to determine the relative class-separability afforded by several different trajectory representations for a range of datasets. The results obtained suggest that the choice of representation makes a small but consistent difference to class separability, indicating that cubic B-Spline control points (fitted using least-squares regression) provide a good choice for use in subsequent experiments. The proposed semi-supervised learning framework is tested on three different real trajectory datasets. In all cases the rate of human intervention requests drops steadily, reaching a usefully low level of ∼ 1% in one case. A further experiment indicates that once a sufficient number of interventions has been provided, a high level of classification performance can be achieved even if subsequent requests are ignored. The automatic incorporation of unlabelled data is shown to improve classification performance in all cases, while a high level of classification performance is maintained even when unlabelled data containing a high proportion of anomalous examples is presented.


Since 1978, the United States and other nations have been pushing to eliminate highly enriched uranium (HEU)—which a terrorist or rogue nation could use to make a bomb—as fuel in civilian research reactors. But achieving that goal will take far longer than previously hoped, according to a study from the National Academies of Sciences, Engineering, and Medicine. Instead of 2018, a timeframe of 2035 is more realistic, the 28 January report concludes. Dozens of civilian research reactors have closed or converted from HEU—uranium enriched to at least 20% of the fissile isotope U-235—to safer low enriched uranium (LEU), including 28 since 2009. But 74 of them still rely on HEU, and developing an LEU replacement fuel for them will take another 12 to 17 years, the report says. Moreover, Russia has expressed little interest in converting its 32 research reactors. Most controversially, as an interim step the report calls for converting the eight U.S. research reactors from running on 93% enriched weapons-grade uranium to 45% enriched HEU. Some nonproliferation experts argue that move would perpetuate commerce in HEU and torpedo the development the LEU fuel.


In recent decades, there has been a rapid growth in consumer awareness of the influence of corporate activities on the environment, and society at large. Firms operating in the food supply chain have not been exempted: the vulnerability of agrifood businesses towards public opinion incentivizes firms to implement social, environmental and ethical measures in collaboration with the other food supply chain stakeholders. Previous studies in the food sector have shown that corporate social responsibility has positive effects on firm performance, but what is still unclear is whether, and how much, consumers are willing to pay for such an intangible attribute. In tackling this issue, we attempt to offer insights into consumer willingness to pay for corporate social responsibility attributes, identifying the psychological constructs that are likely to influence consumer preferences. Our contingent valuation experiment involving Italian consumers shows that individual values behave as effective determinants of consumer willingness to pay for corporate social responsibility.


BACKGROUND
The purpose of this study was to investigate the effects of polymorphisms in CYP3A5*3, CYP3AP1, and MDR1, and of haplotype, on plasma levels of tacrolimus in Chinese patients after renal transplantation, and to assess the relationship between polymorphisms and the variability of concentration/dose of tacrolimus for optimization and individualization regimens.

MATERIAL/METHODS
The MALDI-TOF method was used to detect the genotype of CYP3A5*3, CYP3AP1, and MDR-1 in kidney transplant recipients (n=63) receiving tacrolimus. Patients were assigned to 3 groups according to genotype. Peripheral blood was collected and the serum concentrations of tacrolimus were determined by EMIT 2000 after 12 hours of administration. Dose-adjusted concentrations of tacrolimus were calculated according to the different groups.

RESULTS
We found that tacrolimus dose-adjusted C0 was larger in CYP3A5*3 and CYP3AP1 non-expressing renal transplant patients than in those who expressed the genes. In addition, wild-type homozygotes for MDR1 C3435T had a slightly lower dose-adjusted C0 compared with heterozygotes. However, no evidence was found that there was relationship between the MDR1 1236CT, 2677GT or haplotype polymorphisms and tacrolimus pharmacokinetics.

CONCLUSIONS
The CYP3A5 genotype shows the most important association with tacrolimus concentrations. Our study suggests that a pharmacogenetic approach could be employed to predict individual drug availability differences in future.


This study was designed to determine the comparative creativity of learners who follow PjBL in the environment around with students who follow PjBL in the classroom. The study was conducted from May 2016 to May 2017. The study used a descriptive approach with experimental research type. Design in research is simple factorial design 2x2. The sample of the study amounted to 121 students. The instrument of research in the form of observation sheet of creativity of learners. Data were analyzed by the non-parametric statistical test of Mann Whitney U at a significant level of 0.05. The results showed that the creativity of students Z = 9.179 and Z = 7.563 which means the value of Z ˃ Z-table =1,96 means that the application of PjBL model in the class and in the environment has a significant effect on the creativity of the students. It can conclude that students who follow PjBL in the environment show significantly better creativity than students who follow PjBL in the classroom.


Following the death of Singapore's founding leader Lee Kuan Yew in March 2015, China remains obsessed with Singapore, the only country in the region to achieve advanced economic industrialization without undergoing substantial political liberalization. The key "lesson" that China is trying to learn is how to combine authoritarian rule with "good governance" ("meritocratic" one-party rule). The impact of the "Singapore model" on China shows that learning by nondemocratic states is not necessarily a short-term "modular" phenomenon that is largely reactive in character, but can be long-term and highly institutionalized. It has become increasingly clear, however, that China sees what it wants to see in Singapore, making the "lessons" learned more caricature than reality. And China's recent crackdown on dissenters, squeezing the already limited political space allowed during the post–Tiananmen Square Massacre period, is actually moving the country further away from rather than toward the Singapore model.


The recent analysis developed by professor William H. Page on the US notion of concerted actions raised the idea to develop an article that exams in-death the EU meaning of concerned practices and that skein of US doctrines that focus on several phenomena running from facilitating practices to invitations to collude, plus factors and agreements to exchange information. According to professor Page, the current definition of concerted actions misses the opportunity to use inter-firm communications as the discriminating factor between cases of collusive pricing practices and cases of interdependent parallel behaviors that result in the same market price. To the contrary, the current EU definition of concerted practices accomplishes this purpose. By characterizing strategic inter-firm contacts as one of its building blocks, this notion supplies antitrust enforcers with a theoretical tool that tells lawful oligopolistic interdependence apart from unlawful collusive conduct. Yet, the current EU definition of concerted practices does something more. By encompassing a very strong presumption—that firms exchanging strategic information cannot do anything else but accordingly shape their internal decisions as to prices— this notion catches cartels that appear only from these strategic inter-firm contacts, regardless of their price market conduct. Therefore, the current EU notion of concerted practices is a very powerful prosecuting tool that, as such, deserves to dialog with the US antitrust tradition. Having analyzed the US case law about interdependence, parallelism and exchanges of information, we hence discus whether and how to bridge the EU and US experiences.


1. The activities of the enzymes involved in catecholamine synthesis, tyrosine hydroxylase, aromatic amino acid decarboxylase and dopamine β-hydroxylase, were markedly enhanced in homogenates of phaeochromocytoma compared with human adrenal medulla homogenates measured under optimum substrate concentrations. 2. It was demonstrated in fresh tumour slices that the rate of formation of dopamine (3,4-dihydroxyphenethylamine) from tyrosine was much slower than the rate of formation of dopamine from dopa (3,4-dihydroxyphenylalanine) (suggesting that tyrosine hydroxylase was the rate-limiting enzyme in noradrenaline synthesis in phaeochromocytoma) and that the tyrosine hydroxylation step was still susceptible to end-product inhibition by catecholamines. 3. It is suggested that catecholamine overproduction in phaeochromocytoma is due to the increased activities of catecholamine synthetic enzymes rather than to an insensitivity of tyrosine hydroxylase to end-product inhibition. 4. The activities of the enzymes involved in catecholamine catabolism, monoamine oxidase and perhaps catecholamine O-methyltransferase, were reduced in phaeochromocytoma. This finding provides a biochemical basis for the previous published observations of nonexocytotic release of catecholamines in these tumours. Thus excess amounts of newly synthesized noradrenaline which cannot be stored in the filled catecholamine storage vesicles may not be degraded owing to the reduced monoamine oxidase activity and could diffuse from the phaeochromocytoma into the circulation.