In vivo analysis of the 3′ untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone

Large sections of the 3′ untranslated region (UTR) of hepatitis C virus (HCV) were deleted from an infectious cDNA clone, and the RNA transcripts from seven deletion mutants were tested sequentially for infectivity in a chimpanzee. Mutants lacking all or part of the 3′ terminal conserved region or the poly(U–UC) region were unable to infect the chimpanzee, indicating that both regions are critical for infectivity in vivo. However, the third region, the variable region, was able to tolerate a deletion that destroyed the two putative stem–loop structures within this region. Mutant VR-24 containing a deletion of the proximal 24 nt of the variable region of the 3′ UTR was viable in the chimpanzee and seemed to replicate as well as the undeleted parent virus. The chimpanzee became viremic 1 week after inoculation with mutant VR-24, and the HCV genome titer increased over time during the early acute infection. Therefore, the poly(U–UC) region and the conserved region, but not the variable region, of the 3′ UTR seem to be critical for in vivo infectivity of HCV.

Analysis of the interaction of ZAP-70 and syk protein-tyrosine kinases with the T-cell antigen receptor by plasmon resonance.

Tyrosine phosphorylation of a 17-amino acid immunoreceptor tyrosine-based activation motif (ITAM), conserved in each of the signaling subunits of the T-cell antigen receptor (TCR), mediates the recruitment of ZAP-70 and syk protein-tyrosine kinases (PTKs) to the activated receptor. The interaction between the two tandemly arranged Src-homology 2 (SH2) domains of this family of PTKs and each of the phosphotyrosine-containing ITAMs was examined by real-time measurements of kinetic parameters. The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. Both PTKs bound with ka and Kd values of 5 x 10(6) M-1.sec-1 and approximately 25 nM, respectively. Bindings to the other TCR ITAMs (zeta 1, zeta 2, gamma, and delta ITAMs) were comparable, although the zeta 3 ITAM bound approximately 2.5-fold less well. Studies of the affinity of a single functional SH2 domain of ZAP-70 provided evidence for the cooperative nature of binding of the dual SH2 domains. Mutation of either single SH2 domain decreased the Kd by > 100-fold. Finally, the critical features of the ITAM for syk binding were found to be similar to those required for ZAP-70 binding. These data provide insight into the mechanism by which the multisubunit TCR interacts with downstream effector molecules.

Critical properties of the four-state commutative random permutation glassy Potts model in three and four dimensions

We investigate the critical properties of the four-state commutative random permutation glassy Potts model in three and four dimensions by means of Monte Carlo simulations and a finite-size scaling analysis. By using a field programmable gate array, we have been able to thermalize a large number of samples of systems with large volume. This has allowed us to observe a spin-glass ordered phase in d=4 and to study the critical properties of the transition. In d=3, our results are consistent with the presence of a Kosterlitz-Thouless transition, but also with different scenarios: transient effects due to a value of the lower critical dimension slightly below 3 could be very important.

The Vernacular Discourse of the "Arab Spring:" An Analysis of the Visual, the Embodied, and the Textual Rhetorics of the Karama Revolution

The Vernacular Discourse of the "Arab Spring" is a project that bridges the divide between the East and the West by offering new readings to Arab subjectivities. Through an analysis of the "Arab Spring" through the lens of vernacular discourse, it challenges the Euro-Americo-centric legacies of Orientalism in Western academia and the new wave of extremism in the Arab world by offering alternative representations of Arab bodies and subjectivities. To offer this new reading of the "Arab Spring," it explores the foundations of critical rhetoric as a theory and a practice and argues for a turn towards a critical vernacular discourse. The turn towards critical vernacular discourse is important as it urges the analyses of different artifacts produced by marginalized groups in order to understand their perspectives that have largely been foreclosed in traditional cultural studies research. Building on embodied/performative critical rhetoric, the vernacular discourses of the Arab revolutionary body examines other forms of knowledge productions that are not merely textual; more specifically, through data gathered in the Lhbib Bourguiba, Tunisia. This analysis of the political revolutionary body unveils the complexity underlining the discussion around issues of identity, agency and representation in the Middle East and North Africa, and calls for a critical study towards these issues in the region beyond the binary approach that has been practiced and applied by academics and media analysts. Hence, by analyzing vernacular discourse, this research locates a method of examining and theorizing the dialectic between agency, citizenry, and subjectivity through the study of how power structure is recreated and challenged through the use of the vernacular in revolutionary movements, as well as how marginalized groups construct their own subjectivities through the use of vernacular discourse. Therefore, highlighting the political prominence of evaluating the Arab Spring as a vernacular discourse is important in creating new ways of understanding communication in postcolonial/neocolonial settings.

The Critical Strips of the Sums 1 + 2z + ... + nz

We give a partition of the critical strip, associated with each partial sum 1 + 2z + ... + nz of the Riemann zeta function for Re z < −1, formed by infinitely many rectangles for which a formula allows us to count the number of its zeros inside each of them with an error, at most, of two zeros. A generalization of this formula is also given to a large class of almost-periodic functions with bounded spectrum.

Capital : a critical analysis of capitalist production /

"Works and authors quoted": p. [801]-816.

Functional analysis of the a-defensin disulfide array in mouse cryptdin-4

The alpha-defensin antimicrobial peptide family is defined by a unique tridisulfide array. To test whether this invariant structural feature determines alpha-defensin bactericidal activity, mouse cryptdin-4 (Crp4) tertiary structure was disrupted by pairs of site-directed Ala for Cys substitutions. In a series of Crp4 disulfide variants whose cysteine connectivities were confirmed using NMR spectroscopy and mass spectrometry, mutagenesis did not induce loss of function. To the contrary, the in vitro bactericidal activities of several Crp4 disulfide variants were equivalent to or greater than those of native Crp4. Mouse Paneth cell alpha-defensins require the proteolytic activation of precursors by matrix metalloproteinase-7 (MMP-7), prompting an analysis of the relative sensitivities of native and mutant Crp4 and proCrp4 molecules to degradation by MMP-7. Although native Crp4 and the alpha-defensin moiety of proCrp4 resisted proteolysis completely, all disulfide variants were degraded extensively by MMP-7. Crp4 bactericidal activity was eliminated by MMP-7 cleavage. Thus, rather than determining alpha-defensin bactericidal activity, the Crp4 disulfide arrangement confers essential protection from degradation by this critical activating proteinase.

A critical review of the stress corrosion cracking (SCC) of magnesium alloys

This review aims to provide a foundation for the safe and effective use of magnesium (Mg) alloys, including practical guidelines for the service use of Mg alloys in the atmosphere and/or in contact with aqueous solutions. This is to provide support for the rapidly increasing use of Mg in industrial applications, particularly in the automobile industry. These guidelines should be firmly based on a critical analysis of our knowledge of SCC based on (1) service experience, (2) laboratory testing and (3) understanding of the mechanism of SCC, as well as based on an understanding of the Mg corrosion mechanism.

The communication rights in the information society (CRIS) campaign: Applying social movement theories to an analysis of global media reform

Social movement theories offer useful conceptual and analytical tools to the study and research of global media reform movements. This article is a critical analysis of the Communication Rights in the Information Society (CRIS) campaign. It explores its successes and blind-spots in the light of social movement theory, in particular resource mobilization theory (RMT), and offers practical directions for the movement to move on from where it is to where it ought to be.

A political analysis of the PRSP initiative: Social struggles and the organization of persistent relations of inequality

The current global development project appears to be premised on the assumption that underlying political debates over development have been settled. An upshot of this is that development is reduced to the theoretical, ideological and legal framework of a neo-liberal political order. However, implicit, and sometimes explicit, political dynamics of development can be rendered from a perspective that foregrounds social struggles. I offer a political analysis of the PRSP initiative by examining its evolution and implications considered within social and political contexts, and by specific reference to the 'poverty reduction' interventions that emerged in the 1980s. I argue that the PRSP initiative is best understood as the formation of a comprehensive extension of neo-liberal strategic responses that emerged in the 1980s. In this context, I discuss the example of microcredit schemes in relation to the PRSP process and demonstrate the analytical significance of micro-political social relations for political analyses of development. The approach I adopt reveals social struggles as relationally constitutive of formations of a hegemonic development discourse otherwise ostensibly rendered in de-contextualized terms. From the perspective of critical development analysis such struggles are the concrete expressions of the contradictions immanent to the dialectic of development through inequality and immiseration in the (re)production of social power.

Understanding technology integration in secondary mathematics: Theorising the role of the teacher

Previous research on computers and graphics calculators in mathematics education has examined effects on curriculum content and students’ mathematical achievement and attitudes while less attention has been given to the relationship between technology use and issues of pedagogy, in particular the impact on teachers’ professional learning in specific classroom and school environments. This observation is critical in the current context of educational policy making, where it is assumed – often incorrectly – that supplying schools with hardware and software will increase teachers’ use of technology and encourage more innovative teaching approaches. This paper reports on a research program that aimed to develop better understanding of how and under what conditions Australian secondary school mathematics teachers learn to effectively integrate technology into their practice. The research adapted Valsiner’s concepts of the Zone of Proximal Development, Zone of Free Movement and Zone of Promoted Action to devise a theoretical framework for analysing relationships between factors influencing teachers’ use of technology in mathematics classrooms. This paper illustrates how the framework may be used by analysing case studies of a novice teacher and an experienced teacher in different school settings.

Applying a Systems Approach to the Analysis of the Benefits of Conversion to Organic Production

Although the current level of organic production in industrialised countries amounts to little more than 1-2 percent, it is recognised that one of the major issues shaping agricultural output over the next several decades will be the demand for organic produce (Dixon et al. 2001). In Australia, the issues of healthy food and environmental concern contribute to increasing demand and market volumes for organic produce. However, in Indonesia, using more economical inputs for organic production is a supply-side factor driving organic production. For individual growers and processors, conversion from conventional to organic agriculture is often a challenging step, entailing a thorough revision of established practices and heightened market insecurity. This paper examines the potential for a systems approach to the analysis of the conversion process, to yield insights for household and community decisions. A framework for applying farming systems research to investigate the benefits of organic production in both Australia and Indonesia is discussed. The framework incorporates scope for farmer participation, crucial to the understanding of farming systems; analysis of production; and relationships to resources, technologies, markets, services, policies and institutions in their local cultural context. A systems approach offers the potential to internalise the external effects that may be constraining decisions to convert to organic production, and for the design of decision-making tools to assist households and the community. Systems models can guide policy design and serve as a mechanism for predicting the impact of changes to the policy and market environments. The increasing emphasis of farming systems research on community and environment in recent years is in keeping with the proposed application to organic production, processing and marketing issues. The approach will also facilitate the analysis of critical aspects of the Australian production, marketing and policy environment, and the investigation of these same features in an Indonesian context.

A critical assessment of the finite element method for calculating electric and magnetic fields

The present dissertation is concerned with the determination of the magnetic field distribution in ma[.rnetic electron lenses by means of the finite element method. In the differential form of this method a Poisson type equation is solved by numerical methods over a finite boundary. Previous methods of adapting this procedure to the requirements of digital computers have restricted its use to computers of extremely large core size. It is shown that by reformulating the boundary conditions, a considerable reduction in core store can be achieved for a given accuracy of field distribution. The magnetic field distribution of a lens may also be calculated by the integral form of the finite element rnethod. This eliminates boundary problems mentioned but introduces other difficulties. After a careful analysis of both methods it has proved possible to combine the advantages of both in a .new approach to the problem which may be called the 'differential-integral' finite element method. The application of this method to the determination of the magnetic field distribution of some new types of magnetic lenses is described. In the course of the work considerable re-programming of standard programs was necessary in order to reduce the core store requirements to a minimum.

An analysis of the effect of process parameters on the formability of sheet metal

This investigation is in two parts, theory and experimental verification. (1) Theoretical Study In this study it is, for obvious reasons, necessary to analyse the concept of formability first. For the purpose of the present investigation it is sufficient to define the four aspects of formability as follows: (a) the formability of the material at a critical section, (b) the formability of the material in general, (c) process efficiency, (d) proportional increase in surface area. A method of quantitative assessment is proposed for each of the four aspects of formability. The theoretical study also includes the distinction between coaxial and non-coaxial strains which occur, respectively, in axisymmetrical and unsymmetrical forming processes and the inadequacy of the circular grid system for the assessment of formability is explained in the light of this distinction. (2) Experimental Study As one of the bases of the experimental work, the determination of the end point of a forming process, which sets the limit to the formability of the work material, is discussed. The effects of three process parameters on draw-in are shown graphically. Then the delay of fracture in sheet metal forming resulting from draw-in is analysed in kinematical terms, namely, through the radial displacements, the radial and the circumferential strains, and the projected thickness of the workpiece. Through the equilibrium equation of the membrane stresses, the effect on the shape of the unsupported region of the workpiece, and hence the position of the critical section is explained. Then, the effect of draw-in on the four aspects of formability is discussed throughout this investigation. The triangular coordinate system is used to present and analyse the triaxial strains involved. This coordinate system has the advantage of showing all the three principal strains in a material simultaneously, as well as representing clearly the many types of strains involved in sheet metal work.

An analysis of the role of soft systems methodology in the change process and the contribution of the facilitator within this process

This research aims to examine the effectiveness of Soft Systems Methodology (SSM) to enable systemic change within local goverment and local NHS environments and to examine the role of the facilitator within this process. Checkland's Mode 2 variant of Soft Systems Methodology was applied on an experimental basis in two environments, Herefordshire Health Authority and Sand well Health Authority. The Herefordshire application used SSM in the design of an Integrated Care Pathway for stroke patients. In Sandwell, SSM was deployed to assist in the design of an Infonnation Management and Technology (IM&T) Strategy for the boundary-spanning Sandwell Partnership. Both of these environments were experiencing significant organisational change as the experiments unfurled. The explicit objectives of the research were: To examine the evolution and development of SSM and to contribute to its further development. To apply the Soft Systems Methodology to change processes within the NHS. To evaluate the potential role of SSM in this wider process of change. To assess the role of the researcher as a facilitator within this process. To develop a critical framework through which the impact of SSM on change might be understood and assessed. In developing these objectives, it became apparent that there was a gap in knowledge relating to SSM. This gap concerns the evaluation of the role of the approach in the change process. The case studies highlighted issues in stakeholder selection and management; the communicative assumptions in SSM; the ambiguous role of the facilitator; and the impact of highly politicised problem environments on the effectiveness of the methodology in the process of change. An augmented variant on SSM that integrates an appropriate (social constructivist) evaluation method is outlined, together with a series of hypotheses about the operationalisation of this proposed method.