Experimental requirements for Grover's algorithm in optical quantum computation

The field of linear optical quantum computation (LOQC) will soon need a repertoire of experimental milestones. We make progress in this direction by describing several experiments based on Grover's algorithm. These experiments range from a relatively simple implementation using only a single nonscalable controlled- NOT (CNOT) gate to the most complex, requiring two concatenated scalable CNOT gates, and thus form a useful set of early milestones for LOQC. We also give a complete description of basic LOQC using polarization-encoded qubits, making use of many simplifications to the original scheme of Knill, Laflamme, and Milburn [E. Knill, R. Laflamme, and G. J. Milburn, Nature (London) 409, 46 (2001)].

Role of glutamic acid 216 in cytochrome P450 2D6 substrate binding and catalysis

Human cytochrome P450 (P450) 2D6 is an important enzyme involved in the metabolism of drugs, many of which are amines or contain other basic nitrogen atoms. Asp301 has generally been considered to be involved in electrostatic docking with the basic substrates, on the basis of previous modeling studies and site-directed mutagenesis. Substitution of Glu216 with a residue other than Asp strongly attenuated the binding of quinidine, bufuralol, and several other P450 2D6 ligands. Catalytic activity with the substrates bufuralol and 4-methoxyphenethylamine was strongly inhibited by neutral or basic mutations at Glu216 (>95%), to the same extent as the substitution of Asn at Asp301. Unlike the Asp301 mutants, the Gln216 mutant (E216Q) retained 40% enzyme efficiency with the substrate spirosulfonamide, devoid of basic nitrogen, suggesting that the substitutions at Glu216 affect binding of amine substrates more than other catalytic steps. Attempts to induce catalytic specificity toward new substrates by substitutions at Asp301 and Glu216 were unsuccessful. Collectively, the results provide evidence for electrostatic interaction of amine substrates with Glu216, and we propose that both of these acidic residues plus at least another residue(s) is (are) involved in binding the repertoire of P450 2D6 ligands.

Alternatives to conventional vaccines - Mediators of innate immunity

Vaccines have been described as weapons of mass protection. The eradication of many diseases is testament to their utility and effectiveness. Nevertheless, many vaccine preventable diseases remain prevalent because of political and economic barriers. Additionally, the effects of immaturity and old age, therapies that incapacitate the adaptive immune system and the multitude of strategies evolved by pathogens to evade immediate or sustained recognition by the mammalian immune system are barriers to the effectiveness of existing vaccines or development of new vaccines. In the front line of defence against the pervasiness of infection are the elements of the innate immune system. Innate immunity is under studied and poorly appreciated. However, in the first days after entry of a pathogen into the body, our entire protective response is dependant upon the various elements of our innate immune repertoire. In spite of, its place as our initial defence against infection, attention is only now turning to strategies which enhance or supplement innate immunity. This review examines the need for and potential of innate immune therapies.

Mentoring as a career guidance activity: Fostering non-traditional career exploration for girls

This paper reports on a short term mentoring project conducted in the Australian state of Queensland to foster non-traditional career exploration for girls in the communications/informa - tion technology industry. The aim of the study was to evaluate the possibilities of a short term mentoring program to foster girls’interest in a non-traditional industry. In addition it sought to exam - ine the viability of mentoring as a career guidance activity in schools. The findings indicate that mentoring could be a worthy addition to the repertoire of career guidance activities offered by schools and that it is a valuable process in promoting non-traditional career exploration for girls.

Contemporaneous fluctuations in T cell responses to persistent herpes virus infections

The classical paradigm for T cell dynamics suggests that the resolution of a primary acute virus infection is followed by the generation of a long-lived pool of memory T cells that is thought to be highly stable. Very limited alteration in this repertoire is expected until the immune system is re-challenged by reactivation of latent viruses or by cross-reactive pathogens. Contradicting this view, we show here that the T cell repertoire specific for two different latent herpes viruses in the peripheral blood displayed significant contemporaneous co-fluctuations of virus-specific CD8(+) T cells. The coordinated responses to two different viruses suggest that the fluctuations within the T cell repertoire may be driven by sub-clinical viral reactivation or a more generalized 'bystander' effect. The later contention was supported by the observation that, while absolute number of CD3(+) T cells and their subsets and also the cell surface phenotype of antigen-specific T cells remained relatively constant, a loss of CD62L expression in the total CD8(+) T cell population was coincident with the expansion of tetramer-positive virus-specific T cells. This study demonstrates that the dynamic process of T cell expansion and contractions in persistent viral infections is not limited to the acute phase of infection, but also continues during the latent phase of infection.

CTL recognition of a bulged viral peptide involves biased TCR selection

MHC class I molecules generally present peptides of 8-10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related alpha beta TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed-side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands.

Teacher responses to the communicative attempts of children with autism

We assessed teacher responses to the communicative attempts of children with autism. Teachers were first interviewed using the Inventory of Potential Communicative Acts (IPCA) to identify behaviors in each child's repertoire that the teachers considered to be communicative. Interview results suggested that the teachers interpreted many of the children's prelinguistic gestures, body movements, and facial expressions, as forms of communication. Naturalistic observations were then conducted in the child's classroom to determine how teachers responded to the children's identified forms of prelinguistic behaviors. The results of these naturalistic observations suggested that the teachers often did not respond to the child's prelinguistic behaviors in ways that acknowledged their communicative intent. Implications of the results on the child's communication development and for intervention efforts are discussed.

An Australian Idol of Modernist Consumerism: Minnie Tittell Brune and the Gallery Girls

The Australian career of the young American actor Minnie Tittell Brune exemplifies the complex cultural and economic forces operating on the institution of live theatre at the beginning of the twentieth century. Brune focalizes the contemporary processes which reconstituted the international institution of mass entertainment out of the traditional cultural practices of theatre. The theatrical star is seen as both engaging with and resisting the commodification of her labour power; image and talent resulting from her ambiguous industrial role as magnetic 'star' and as managerial commodity. However, the iconic and affective power of the actor evokes strong attachment from significant sections of the newly heterosocial popular audience, in particular from the gallery girls, the young female audience who idolized Brune as a performative personality enacting social self-realization and glamorous transformation. Through reading Brume's repertoire, her social persona as 'star' and her 'emotional' performative style, it is demonstrated how artistic retro-glamour, religious evangelicalism and discourses of sexuality and femininity serve to manage theatre's move into the mass-entertainment age.

Comparison of virulence gene profiles of Escherichia coli strains isolated from healthy and diarrheic swine

A combination of uni- and multiplex PCR assays targeting 58 virulence genes (VGs) associated with Escherichia coli strains causing intestinal and extraintestinal disease in humans and other mammals was used to analyze the VG repertoire of 23 commensal E. coli isolates from healthy pigs and 52 clinical isolates associated with porcine neonatal diarrhea (ND) and postweaning diarrhea (PWD). The relationship between the presence and absence of VGs was interrogated using three statistical methods. According to the generalized linear model, 17 of 58 VGs were found to be significant (P < 0.05) in distinguishing between commensal and clinical isolates. Nine of the 17 genes represented by iha, hlyA, aidA, east1, aah, fimH, iroN(E).(coli), traT, and saa have not been previously identified as important VGs in clinical porcine isolates in Australia. The remaining eight VGs code for fimbriae (F4, F5, F18, and F41) and toxins (STa, STh, LT, and Stx2), normally associated with porcine enterotoxigenic E. coli. Agglomerative hierarchical algorithm analysis grouped E. coli strains into subclusters based primarily on their serogroup. Multivariate analyses of clonal relationships based on the 17 VGs were collapsed into two-dimensional space by principal coordinate analysis. PWD clones were distributed in two quadrants, separated from ND and commensal clones, which tended to cluster within one quadrant. Clonal subclusters within quadrants were highly correlated with serogroups. These methods of analysis provide different perspectives in our attempts to understand how commensal and clinical porcine enterotoxigenic E. coli strains have evolved and are engaged in the dynamic process of losing or acquiring VGs within the pig population.

Non-coding RNAs in the nervous system

Increasing evidence suggests that the development and function of the nervous system is heavily dependent on RNA editing and the intricate spatiotemporal expression of a wide repertoire of non-coding RNAs, including micro RNAs, small nucleolar RNAs and longer non-coding RNAs. Non-coding RNAs may provide the key to understanding the multi-tiered links between neural development, nervous system function, and neurological diseases.

TCR{alpha} Genes Direct MHC Restriction in the Potent Human T Cell Response to a Class I-Bound Viral Epitope

The underlying generic properties of {alpha}β TCRs that control MHC restriction remain largely unresolved. To investigate MHC restriction, we have examined the CTL response to a viral epitope that binds promiscuously to two human leukocyte Ags (HLAs) that differ by a single amino acid at position 156. Individuals expressing either HLA-B*3501 (156Leucine) or HLA-B*3508 (156Arginine) showed a potent CTL response to the 407HPVGEADYFEY417 epitope from EBV. Interestingly, the response was characterized by highly restricted TCR β-chain usage in both HLA-B*3501+ and HLA-B*3508+ individuals; however, this conserved TRBV9+ β-chain was associated with distinct TCR {alpha}-chains depending upon the HLA-B*35 allele expressed by the virus-exposed host. Functional assays confirmed that TCR {alpha}-chain usage determined the HLA restriction of the CTLs. Structural studies revealed significant differences in the mobility of the peptide when bound to HLA-B*3501 or HLA-B*3508. In HLA-B*3501, the bulged section of the peptide was disordered, whereas in HLA-B*3508 the bulged epitope adopted an ordered conformation. Collectively, these data demonstrate not only that mobile MHC-bound peptides can be highly immunogenic but can also stimulate an extremely biased TCR repertoire. In addition, TCR {alpha}-chain usage is shown to play a critical role in controlling MHC restriction between closely related allomorphs.

Modulation of insect Cav channels by peptidic spider toxins

Insects have a much smaller repertoire of voltage-gated calcium (Ca-v) channels than vertebrates. Drosophila melanogaster harbors only a single ortholog of each of the vertebrate Ca(v)1, Ca(v)2, and Ca(v)3 subtypes, although its basal inventory is expanded by alternative splicing and editing of Ca-v channel transcripts. Nevertheless, there appears to be little functional plasticity within this limited panel of insect Ca-v channels, since severe loss-of-function mutations in genes encoding the pore-forming a, subunits in Drosophila are embryonic lethal. Since the primary role of spider venom is to paralyze or kill insect prey, it is not surprising that most, if not all, spider venoms contain peptides that potently modify the activity of these functionally critical insect Ca-v channels. Unfortunately, it has proven difficult to determine the precise ion channel subtypes recognized by these peptide toxins since insect Ca-v channels have significantly different pharmacology to their vertebrate counterparts, and cloned insect Ca-v channels are not available for electrophysiological studies. However, biochemical and genetic studies indicate that some of these spider toxins might ultimately become the defining pharmacology for certain subtypes of insect Ca-v channels. This review focuses on peptidic spider toxins that specifically target insect Ca-v channels. In addition to providing novel molecular tools for ion channel characterization, some of these toxins are being used as leads to develop new methods for controlling insect pests. (c) 2006 Elsevier Ltd. All rights reserved.

An online community of practice for pre-service and beginning teachers of secondary mathematics

The aim of this study was to investigate how a community of practice focused on learning to teach secondary mathematics was created and sustained by pre-service and beginning teachers. Bulletin board discussions of one pre-service cohort are analysed in terms of Wenger’s (1998) three defining features of a community of practice: mutual engagement, joint enterprise, and a shared repertoire. The study shows that the emergent design of the community contributed to its sustainability in allowing the pre-service teachers to define their own professional goals and values. Sustainability was also related to how the participants expanded, transformed, and maintained the community during the pre-service program and after graduation.

MASHALIM PARA CONTAR - SUBSÍDIOS PARA A EDUCAÇÃO PARA A PRUDENTIA

Essa pesquisa tem por objetivo estudar o significado e o alcance educativos, por um lado da virtude da prudentia e, por outro, da arte de contar mashalim. O objetivo específico é elaborar uma coletânea que ajude a resgatar a relação prudentia / narrativas na formação de professores de ensino fundamental e médio e também dotar o docente de um material que sirva para que ele mesmo elabore o seu próprio repertório nesse campo. O material aqui apresentado é uma coletânea acompanhada de reflexões filosóficas e pedagógicas, que ajudaram a compreender os valores antropológicos das situações envolvidas. Para isso, apoiamo-nos no referencial teórico clássico de Tomás de Aquino, especialmente em seus estudos sobre essa virtude (Tomás de Aquino, 2005), e em seus intérpretes contemporâneos: Josef Pieper e Jean Lauand. Além disso, foi central a minha experiência pessoal como contadora de histórias que se baseia no psicodramatista Moreno, no biólogo Maturana e em teóricos que têm desenvolvido trabalhos referentes à leitura e escrita para ampliar o diálogo com os professores.

Identities and oppressions: Jean-Claude Lauzon's Léolo (1992)

This article approaches the fragmentation of identities characteristic of contemporary Western societies through the 1992 film Léolo by Jean-Claude Lauzon. Although it does explore linguistic, social, religious and ethnic divisions, this major piece of the Quebec repertoire recasts the sociolinguistic conflict between vernacular and formal practices (Labov 1972; Blanche-Benveniste 2002), raising questions of status and choice. This conflict is subsumed by the dialectics between primary and secondary culture. The cultural and linguistic opposition finds a primary metaphor in the film's central motif of the duality of dream and reality. No more than the cultural and linguistic can this opposition find a synthesis. This impossible reconciliation defines the constitutive rupture of the human psyche itself.