Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

Quantifying the limits of HANPP and carbon emissions which prolong total species well-being

Anthropogenic climate and land-use change are leading to irreversible losses of global biodiversity, upon which ecosystem functioning depends. Since total species' well-being depends on ecosystem goods and services, man must determine how much net primary productivity (NPP) may be appropriated and carbon emitted so as to not adversely impact this and future generations. In 2005, man ought to have only appropriated 9.72 Pg C of NPP, representing a factor 2.50, or 59.93%, reduction in human-appropriated NPP in that year. Concurrently, the carbon cycle would have been balanced with a factor 1.26, or 20.84%, reduction from 7.60 Gt C/year to 5.70 Gt C/year, representing a return to the 1986 levels. This limit is in keeping with the category III stabilization scenario of the Intergovernmental Panel for Climate Change. Projecting population growth to 2030 and its associated basic food requirements, the maximum HANPP remains at 9.74 ± 0.02 Pg C/year. This time-invariant HANPP may only provide for the current global population of 6.51 billion equitably at the current average consumption of 1.49 t C per capita, calling into question the sustainability of developing countries striving for high-consuming country levels of 5.85 t C per capita and its impacts on equitable resource distribution. © Springer Science+Business Media B.V. 2009.

Phylogeny and zoogeography of the cyprinid hemicultrine group (Cyprinidae : Cultrinae)

Ying-Gui Dai and Jun-Xing Yang (2003) Phylogeny and zoogeography of the cyprinid hemicultrine group (Cyprinidae: Cultrinae). Zoological Studies 42(1): 73-92. The hemicultrine group consists of middle-sized cyprinids in Asia which taxonomically belong to the subfamily Cultrinae in the Cyprinidae (Cypriniformes), but there has been no convincing generic phylogenetic hypothesis proposal so far. On the basis of a morphological study of 65 specimens soaked in formalin and 14 skeletal specimens of 8 species in 6 genera within the hemicultrine group as an ingroup, a 70-character matrix was obtained. The generic phylogenetic relationships of the hemicultrine group are hypothesized with the matrix by the method of cladistic analysis. When the species Rasborinus lineatus or Cultrichthys erythropterus is used as the sole outgroup, the matrix gives the same single most-parsimonious tree of generic phylogenetic relationships within the hemicultrine group which shows that the hemicultrine group forms a monophyletic group. However, when Rasborinus lineatus is used as the sole outgroup and Cultrichthys erythropterus and Paralaubuca barroni are included in the ingroup, the hemicultrine group is validated to represent a paraphyletic group, and the hemicultrine group and the genus Paralaubuca form a monophyletic group. The tree of generic relationships and zoogeography of the monophyletic group comprising the hemicultrine group and the genus Paralaubuca suggest the following: (1) The monophyletic group comprises 2 smaller monophyletic groups: the genera Hemiculterella + Pseudohemiculter + Hainania and the genera Hemiculter + Paralaubuca + Pseudolaubuca + Toxabramis. (2) The sister groups of the monophyletic group show both overlapping and vicariant distribution patterns; therefore the generic distribution pattern of the monophyletic group maybe have resulted from both dispersal and vicariance events. (3) The monophyletic group probably originated on the Asian mainland from the Yangtze River to the Pearl River and on Hainan Island in China. (4) The monophyletic group probably originated after the Japanese Archipelago was separated from the Asian mainland at the beginning of the Quaternary Period in the Cenozoic but before Taiwan, Hainan Island, and Indonesia were completely isolated from the Asian mainland after the ice age in the Quaternary Period. (5) Speciation of the genus Hemiculter should have been the earliest, and those of the genera Paralaubuca, Pseudolaubuca, and Hainania ought to be the latest in the process of evolution of this monophyletic group. http://www.sinica.edu.tw/zool/zoolstud/42.1/73.pdf.

coconceptmap: a system for collaborative concept mapping

Concept mapping is a technique for visualizing the relationships between different concepts, and collaborative concept mapping is used to model knowledge and transfer expert knowledge. Because of lacking some features,existing systems can’t support collaborative concept mapping effectively. In this paper, we analysis the collaborative concept mapping process according to the theory of distributed cognition, and argue the functions effective systems ought to include. A collaborative concept mapping system should have the following features: visualization of concept map, flexible collaboration style,supporting natural interaction, knowledge management and history management. Furthermore, we describe every feature in details. Finally,a prototype system has been built to fully explore the above technologies.

植物冠层氮素淋失研究进展

植物冠层在养分循环及改变养分流量方面的作用,是当前国内、外研究的重点和热点课题。本文在综合评述前人研究的基础上,对植物冠层氮素淋失及其影响因素进行了分析,指出现有研究中存在的不足,提出了下一步应重点研究的问题:(1)进一步完善测定方法,开展对农田植物冠层氮素淋失的研究;(2)如果确定农田植物存在冠层氮素淋洗,需明确冠层氮素淋洗形态,并与不同氮效率基因型联系起来进行研究;(3)开展揭示植物冠层氮素淋失途径与过程的机理研究,特别是应该将不同生育期叶面积、气孔密度、气孔导度、叶片自由空间和自由空间中可溶性氮素等可能影响冠层氮素淋洗的指标与冠层氮素淋洗相联系进行研究,有利于揭示冠层氮素淋失机理,对冠层氮素淋失赋予理论支持。

地震波场模拟及叠前深度偏移的李群方法

The processes of seismic wave propagation in phase space and one way wave extrapolation in frequency-space domain, if without dissipation, are essentially transformation under the action of one parameter Lie groups. Consequently, the numerical calculation methods of the propagation ought to be Lie group transformation too, which is known as Lie group method. After a fruitful study on the fast methods in matrix inversion, some of the Lie group methods in seismic numerical modeling and depth migration are presented here. Firstly the Lie group description and method of seismic wave propagation in phase space is proposed, which is, in other words, symplectic group description and method for seismic wave propagation, since symplectic group is a Lie subgroup and symplectic method is a special Lie group method. Under the frame of Hamiltonian, the propagation of seismic wave is a symplectic group transformation with one parameter and consequently, the numerical calculation methods of the propagation ought to be symplectic method. After discrete the wave field in time and phase space, many explicit, implicit and leap-frog symplectic schemes are deduced for numerical modeling. Compared to symplectic schemes, Finite difference (FD) method is an approximate of symplectic method. Consequently, explicit, implicit and leap-frog symplectic schemes and FD method are applied in the same conditions to get a wave field in constant velocity model, a synthetic model and Marmousi model. The result illustrates the potential power of the symplectic methods. As an application, symplectic method is employed to give synthetic seismic record of Qinghai foothills model. Another application is the development of Ray+symplectic reverse-time migration method. To make a reasonable balance between the computational efficiency and accuracy, we combine the multi-valued wave field & Green function algorithm with symplectic reverse time migration and thus develop a new ray+wave equation prestack depth migration method. Marmousi model data and Qinghai foothills model data are processed here. The result shows that our method is a better alternative to ray migration for complex structure imaging. Similarly, the extrapolation of one way wave in frequency-space domain is a Lie group transformation with one parameter Z and consequently, the numerical calculation methods of the extrapolation ought to be Lie group methods. After discrete the wave field in depth and space, the Lie group transformation has the form of matrix exponential and each approximation of it gives a Lie group algorithm. Though Pade symmetrical series approximation of matrix exponential gives a extrapolation method which is traditionally regarded as implicit FD migration, it benefits the theoretic and applying study of seismic imaging for it represent the depth extrapolation and migration method in a entirely different way. While, the technique of coordinates of second kind for the approximation of the matrix exponential begins a new way to develop migration operator. The inversion of matrix plays a vital role in the numerical migration method given by Pade symmetrical series approximation. The matrix has a Toepelitz structure with a helical boundary condition and is easy to inverse with LU decomposition. A efficient LU decomposition method is spectral factorization. That is, after the minimum phase correlative function of each array of matrix had be given by a spectral factorization method, all of the functions are arranged in a position according to its former location to get a lower triangular matrix. The major merit of LU decomposition with spectral factorization (SF Decomposition) is its efficiency in dealing with a large number of matrixes. After the setup of a table of the spectral factorization results of each array of matrix, the SF decomposition can give the lower triangular matrix by reading the table. However, the relationship among arrays is ignored in this method, which brings errors in decomposition method. Especially for numerical calculation in complex model, the errors is fatal. Direct elimination method can give the exact LU decomposition But even it is simplified in our case, the large number of decomposition cost unendurable computer time. A hybrid method is proposed here, which combines spectral factorization with direct elimination. Its decomposition errors is 10 times little than that of spectral factorization, and its decomposition speed is quite faster than that of direct elimination, especially in dealing with a large number of matrix. With the hybrid method, the 3D implicit migration can be expected to apply on real seismic data. Finally, the impulse response of 3D implicit migration operator is presented.

Sopravvenienze e rimedi nel contratto d'appalto: la previsione del cosiddetto obbligo di rinegoziazione

In this thesis I study how the legal system reacts (or ought to react) to unforeseen circumstances that interfere with the functioning of long term contractual relationships. More precisely, I investigate whether mandatory renegotiation would be an appropriate tool to guarantee the flexibility that long-term relationships require. Furthermore, after having analyzed the instruments that our legal system offers to preserve long-term contractual relationships, I explore the solutions adopted by other legal systems. This comparative analysis helps to formulate normative proposals to improve the functioning of our legal system.

JUSTEIS: JISC Usage Surveys: Trends in Electronic Information Services Final report 2003/2004 Cycle Five

Urquhart, C., Spink, S., Thomas, R., Yeoman, A., Durbin, J., Turner, J., Fenton, R. & Armstrong, C. (2004). JUSTEIS: JISC Usage Surveys: Trends in Electronic Information Services Final report 2003/2004 Cycle Five. Aberystwyth: Department of Information Studies, University of Wales Aberystwyth. Sponsorship: JISC

Getting Constitutional Theory into Proportion: A Matter of Interpretation?

Gibbs, N., Getting Constitutional Theory into Proportion: A Matter of Interpretation?, Oxford Journal of Legal Studies, 27 (1), 175-191. RAE2008

Synthetic biology: a utilitarian perspective

I examine the positive and negative features of synthetic biology (‘SynBio’) from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a ‘precautionary’ approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio.

Korespondencja sztuk w dydaktyce szkoły ponadgimnazjalnej. Diagnoza i propozycje

Instytut Filologii Polskiej: Zakład Dydaktyki Literatury i Języka Polskiego

On Apologizing in Norwegian

This paper discusses selected points concerning the verbal realization of the speech act of apology in Norwegian. It sets out to establish prevailing tendencies in the choice of apology strategies applied by the native speakers of Norwegian. The present findings, which seem to indicate that Norwegian apology strategies are fairly routinized, ought to be perceived as preliminary as a more detailed analysis of apology formulae will be presented in an upcoming article.

Development of a general internet attitude scale and internet self-efficacy scale

The measurement of users’ attitudes towards and confidence with using the Internet is an important yet poorly researched topic. Previous research has encountered issues that serve to obfuscate rather than clarify. Such issues include a lack of distinction between the terms ‘attitude’ and ‘self-efficacy’, the absence of a theoretical framework to measure each concept, and failure to follow well-established techniques for the measurement of both attitude and self-efficacy. Thus, the primary aim of this research was to develop two statistically reliable scales which independently measure attitudes towards the Internet and Internet self-efficacy. This research addressed the outlined issues by applying appropriate theoretical frameworks to each of the constructs under investigation. First, the well-known three component (affect, behaviour, cognition) model of attitudes was applied to previous Internet attitude statements. The scale was distributed to four large samples of participants. Exploratory factor analyses revealed four underlying factors in the scale: Internet Affect, Internet Exhilaration, Social Benefit of the Internet and Internet Detriment. The final scale contains 21 items, demonstrates excellent reliability and achieved excellent model fit in the confirmatory factor analysis. Second, Bandura’s (1997) model of self-efficacy was followed to develop a reliable measure of Internet self-efficacy. Data collected as part of this research suggests that there are ten main activities which individuals can carry out on the Internet. Preliminary analyses suggested that self-efficacy is confounded with previous experience; thus, individuals were invited to indicate how frequently they performed the listed Internet tasks in addition to rating their feelings of self-efficacy for each task. The scale was distributed to a sample of 841 participants. Results from the analyses suggest that the more frequently an individual performs an activity on the Internet, the higher their self-efficacy score for that activity. This suggests that frequency of use ought to be taken into account in individual’s self-efficacy scores to obtain a ‘true’ self-efficacy score for the individual. Thus, a formula was devised to incorporate participants’ previous experience of Internet tasks in their Internet self-efficacy scores. This formula was then used to obtain an overall Internet self-efficacy score for participants. Following the development of both scales, gender and age differences were explored in Internet attitudes and Internet self-efficacy scores. The analyses indicated that there were no gender differences between groups for Internet attitude or Internet self-efficacy scores. However, age group differences were identified for both attitudes and self-efficacy. Individuals aged 25-34 years achieved the highest scores on both the Internet attitude and Internet self-efficacy measures. Internet attitude and self-efficacy scores tended to decrease with age with older participants achieving lower scores on both measures than younger participants. It was also found that the more exposure individuals had to the Internet, the higher their Internet attitude and Internet self-efficacy scores. Examination of the relationship between attitude and self-efficacy found a significantly positive relationship between the two measures suggesting that the two constructs are related. Implication of such findings and directions for future research are outlined in detail in the Discussion section of this thesis.

Gold mining in the Peruvian Amazon: global prices, deforestation, and mercury imports.

Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006-2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R(2) = 0.93, p = 0.04, 2003-2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground.

Likelihood, entropy and species diversity; some comparisons in a Sumatran forest

In attempts to conserve the species diversity of trees in tropical forests, monitoring of diversity in inventories is essential. For effective monitoring it is crucial to be able to make meaningful comparisons between different regions, or comparisons of the diversity of a region at different times. Many species diversity measures have been defined, including the well-known abundance and entropy measures. All such measures share a number of problems in their effective practical use. However, probably the most problematic is that they cannot be used to meaningfully assess changes, since thay are only concerned with the number of species or the proportions of the population/sample which they constitute. A natural (though simplistic) model of a species frequency distribution is the multinomial distribution. It is shown that the likelihood analysis of samples from such a distribution are closely related to a number of entropy-type measures of diversity. Hence a comparison of the species distribution on two plots, using the multinomial model and likelihood methods, leads to generalised cross-entropy as the LRT test statistic of the null that the species distributions are the same. Data from 30 contiguous plots in a forest in Sumatra are analysed using these methods. Significance tests between all pairs of plots yield extremely low p-values, indicating strongly that it ought to been "Obvious" that the observed species distributions are different on different plots. In terms of how different the plots are, and how these differences vary over the whole study site, a display of the degrees of freedom of the test, (equivalent to the number of shared species) seems to be the most revealing indicator, as well as the simplest.