Structural basis for the function of anti-idiotypic antibody in immune memory

We had earlier proposed a hypothesis to explain the mechanism of perpetuation of immunological memory based on the operation of idiotypic network in the complete absence of antigen. Experimental evidences were provided for memory maintenance through anti-idiotypic antibody (Ab(2)) carrying the internal image of the antigen. In the present work, we describe a structural basis for such memory perpetuation by molecular modeling and structural analysis studies. A three-dimensional model of Ab(2) was generated and the structure of the antigenic site on the hemagglutinin protein H of Rinderpest virus was modeled using the structural template of hemagglutinin protein of Measles virus. Our results show that a large portion of heavy chain containing the CDR regions of Ab(2) resembles the domain of the hemagglutinin housing the epitope regions. The similarity demonstrates that an internal image of the H antigen is formed in Ab(2), which provides a structural basis for functional mimicry demonstrated earlier. This work brings out the importance of the structural similarity between a domain of hemagglutinin protein to that of its corresponding Ab(2). It provides evidence that Ab(2) is indeed capable of functioning as surrogate antigen and provides support to earlier proposed relay hypothesis which has provided a mechanism for the maintenance of immunological memory.

Flow of metal into the flash gap in the last stages of a plane-strain closed-die forging operation

In closed-die forging the flash geometry should be such as to ensure that the cavity is completely filled just as the two dies come into contact at the parting plane. If metal is caused to extrude through the flash gap as the dies approach the point of contact — a practice generally resorted to as a means of ensuring complete filling — dies are unnecessarily stressed in a high-stress regime (as the flash is quite thin and possibly cooled by then), which reduces the die life and unnecessarily increases the energy requirement of the operation. It is therefore necessary to carefully determine the dimensions of the flash land and flash thickness — the two parameters, apart from friction at the land, which control the lateral flow. The dimensions should be such that the flow into the longitudinal cavity is controlled throughout the operation, ensuring complete filling just as the dies touch at the parting plane. The design of the flash must be related to the shape and size of the forging cavity as the control of flow has to be exercised throughout the operation: it is possible to do this if the mechanics of how the lateral extrusion into the flash takes place is understood for specific cavity shapes and sizes. The work reported here is part of an ongoing programme investigating flow in closed-die forging. A simple closed shape (no longitudinal flow) which may correspond to the last stages of a real forging operation is analysed using the stress equilibrium approach. Metal from the cavity (flange) flows into the flash by shearing in the cavity in one of the three modes considered here: for a given cavity the mode with the least energy requirement is assumed to be the most realistic. On this basis a map has been developed which, given the depth and width of the cavity as well as the flash thickness, will tell the designer of the most likely mode (of the three modes considered) in which metal in the cavity will shear and then flow into the flash gap. The results of limited set of experiments, reported herein, validate this method of selecting the optimum model of flow into the flash gap.

Optimal sign tests for data from ranked set samples

This paper considers the one-sample sign test for data obtained from general ranked set sampling when the number of observations for each rank are not necessarily the same, and proposes a weighted sign test because observations with different ranks are not identically distributed. The optimal weight for each observation is distribution free and only depends on its associated rank. It is shown analytically that (1) the weighted version always improves the Pitman efficiency for all distributions; and (2) the optimal design is to select the median from each ranked set.

Effects of variance-function misspecification in analysis of longitudinal data

The approach of generalized estimating equations (GEE) is based on the framework of generalized linear models but allows for specification of a working matrix for modeling within-subject correlations. The variance is often assumed to be a known function of the mean. This article investigates the impacts of misspecifying the variance function on estimators of the mean parameters for quantitative responses. Our numerical studies indicate that (1) correct specification of the variance function can improve the estimation efficiency even if the correlation structure is misspecified; (2) misspecification of the variance function impacts much more on estimators for within-cluster covariates than for cluster-level covariates; and (3) if the variance function is misspecified, correct choice of the correlation structure may not necessarily improve estimation efficiency. We illustrate impacts of different variance functions using a real data set from cow growth.

General ranked set sampling with cost considerations

Nahhas, Wolfe, and Chen (2002, Biometrics 58, 964-971) considered optimal set size for ranked set sampling (RSS) with fixed operational costs. This framework can be very useful in practice to determine whether RSS is beneficial and to obtain the optimal set size that minimizes the variance of the population estimator for a fixed total cost. In this article, we propose a scheme of general RSS in which more than one observation can be taken from each ranked set. This is shown to be more cost-effective in some cases when the cost of ranking is not so small. We demonstrate using the example in Nahhas, Wolfe, and Chen (2002, Biometrics 58, 964-971), by taking two or more observations from one set even with the optimal set size from the RSS design can be more beneficial.

Efficient regression analysis with ranked-set sampling

This article is motivated by a lung cancer study where a regression model is involved and the response variable is too expensive to measure but the predictor variable can be measured easily with relatively negligible cost. This situation occurs quite often in medical studies, quantitative genetics, and ecological and environmental studies. In this article, by using the idea of ranked-set sampling (RSS), we develop sampling strategies that can reduce cost and increase efficiency of the regression analysis for the above-mentioned situation. The developed method is applied retrospectively to a lung cancer study. In the lung cancer study, the interest is to investigate the association between smoking status and three biomarkers: polyphenol DNA adducts, micronuclei, and sister chromatic exchanges. Optimal sampling schemes with different optimality criteria such as A-, D-, and integrated mean square error (IMSE)-optimality are considered in the application. With set size 10 in RSS, the improvement of the optimal schemes over simple random sampling (SRS) is great. For instance, by using the optimal scheme with IMSE-optimality, the IMSEs of the estimated regression functions for the three biomarkers are reduced to about half of those incurred by using SRS.

The Saintly Madman : A Study of the Scholarly Reception History of Buile Shuibhne

This study examines the scholarly reception history of an early Irish text, Buile Shuibhne (The Frenzy of Suibhne), by focusing on the various theoretical and methodological presuppositions which have determined the scholars’ understanding of the text’s religious allegorical significance in the course of the 20th century. The reception-oriented inquiry takes the intersubjective aspect of literary interpretation as the basis for accentuating the importance of communally shared presumptions and reading strategies in the explication of interpretive variety. The materials of the study have been divided into four frameworks of interpretation: historical, pre-Christian, Christian and anthropological. This heuristic division does not denote mutually exclusive paradigms, but rather refers to perceived similarities within each group regarding the questions posed, and the evidence adduced, in textual analysis. The historical framework concentrates on the issues of the origins of the tale and the possible historicity of its main protagonist. The pre-Christian framework covers the theories of the shamanic, Indo-European and Celtic elements in the text, whereas the Christian framework includes readings emphasising the biblical, monastic and ascetic aspects of the tale. The anthropological framework in turn focuses on the parallels drawn between the narrative and the universal structure of the rites of passage. In addition to the examination of these four frameworks, the study also links the question of methodology with wider issues of authorship and textual integrity, and critically reconsiders the manner in which J.G. O'Keeffe's 1913 edition of the text has been reified in previous scholarship as a representation of a 12th century authorial original. The overall objective of the present case-study is to relate theoretical conceptions of literary theory, comparative religion and historiography to the study of early Irish narrative material by considering the communal and institutional dimension of meaning-making, and the implications of comparative methodology for historical research. In this aim, the prevailing methodological presuppositions informing the scholarly discourse on Buile Shuibhne are set against the wider context of Celtic Studies scholarship, in order to draw attention to the need to critically reflect upon the operations of knowledge production in future research.

The Homeless Etiquette : Social Interaction and Behavior Among the Homeless in Taito Ward, Tokyo

The thesis focuses on the social interaction and behavior of the homeless living in Tokyo's Taito Ward. The study is based on the author's own ethnographic field research carried out in the autumn 2003. The chosen methodologies were based on the methodology called "participant observation", and they were used depending on the context. The ethnographic field research was carried out from the mid-August to the beginning of the October in 2003. The most important targets of the research were three separate loosely knit groups placed in certain parts of Taito Ward. One of these groups was based in proximity to the Ueno train station, one group gathered every morning around a homeless support organization called San'yûkai, and one was based in Tamahime Park located in the old San'ya area of Tokyo. The analysis is based on the aspects of Takie Sugiyama Lebra's theory of "social relativism". Lebra's theory consists of the following, arguably universal aspects: belongingness, empathy, dependence, place in the society, and reciprocity. In addition, all the interaction and behavior is tied to the context and the situation. According to Lebra, ritual and intimate situations produce similar action, which is socially relative. Of these, the norms of the ritual behavior are more regulated, while the intimate bahavior is less spontaneous. On the contrary, an anomic situation produces anomic behavior, which is not socially relative. Lebra's theory is critically reviewed by the author of the thesis, and the author has attempted to modify the theory to make it more adaptable to the present-day society and to the analysis. Erving Goffman's views of the social interaction and Anthony Giddens' theories about the social structures have been used as complementary thoretical basis. The aim of the thesis is to clarify, how and why the interaction and the behavior of some homeless individuals in some situations follow the aspects of Lebra's "social relativism", and on the other hand, why in some situations they do not. In the latter cases the answers can be sought from regional and individual differences, or from the inaptness of the theory to analyze the presented situation. Here, a significant factor is the major finding of the field study: the so called "homeless etiquette", which is an abstract set of norms and values that influences the social interaction and behavior of the homeless, and with which many homeless individuals presented in the study complied. The fundamental goal of the thesis is to reach profound understanding about the daily life of the homeless, whose lives were studied. The author argues that this kind of profound understanding is necessary in looking for sustainable solutions in the areas of social and housing policy to improve the position of the homeless and the qualitative functioning of the society.

Problems of Proto-Slavic Historical Nominal Morphology : On the Basis of Old Church Slavic

In this study I offer a diachronic solution for a number of difficult inflectional endings in Old Church Slavic nominal declensions. In this context I address the perhaps most disputed and the most important question of the Slavic nominal inflectional morphology: whether there was in Proto-Slavic an Auslautgesetz (ALG), a law of final syllables, that narrowed the Proto-Indo-European vowel */o/ to */u/ in closed word-final syllables. In addition, the work contains an exhaustive morphological classification of the nouns and adjectives that occur in canonical Old Church Slavic. I argue that Proto-Indo-European */o/ became Proto-Slavic */u/ before word-final */s/ and */N/. This conclusion is based on the impossibility of finding credible analogical (as opposed to phonological) explanations for the forms supporting the ALG hypothesis, and on the survival of the neuter gender in Slavic. It is not likely that the */o/-stem nominative singular ending */-u/ was borrowed from the accusative singular, because the latter would have been the only paradigmatic form with the stem vowel */-u-/. It is equally unlikely that the ending */-u/ was borrowed from the */u/-stems, because the latter constituted a moribund class. The usually stated motivation for such an analogical borrowing, i.e. a need to prevent the merger of */o/-stem masculines with neuters of the same class, is not tenable. Extra-Slavic, as well as intra-Slavic evidence suggests that phonologically-triggered mergers between two semantically opaque genders do not tend to be prevented, but rather that such mergers lead to the loss of the gender opposition in question. On the other hand, if */-os/ had not become */-us/, most nouns and, most importantly, all adjectives and pronouns would have lost the formal distinction between masculines and neuters. This would have necessarily resulted in the loss of the neuter gender. A new explanation is given for the most apparent piece of evidence against the ALG hypothesis, the nominative-accusative singular of the */es/-stem neuters, e.g. nebo 'sky'. I argue that it arose in late Proto-Slavic dialects, replacing regular nebe, under the influence of the */o/- and */yo/-stems where a correlation had emerged between a hard root-final consonant and the termination -o, on the one hand, and a soft root-final consonant and the termination -e, on the other.

Adsorption isitherms for neutral organic compounds-A hierarchy in modelling: Part IV. Charge of maximum adsorption-Statistical mechanical basis

The charge at which adsorption of orgamc compounds attains a maximum ( \sigma MAX M) at an electrochenucal interface is analysed using several multi-state models in a hierarchical manner The analysis is based on statistical mechamcal results for the following models (A) two-state site parity, (B) two-state muhl-slte, and (C) three-state site parity The coulombic interactions due to permanent and reduced dipole effects (using mean field approximation), electrostatic field effects and specific substrate interactions have been taken into account. The simplest model in the hierarchy (two-state site parity) yields the exphcit dependence of ( \sigma MAX M) on the permanent dipole moment, polarizability of the solvent and the adsorbate, lattice spacing, effective coordination number, etc Other models in the baerarchy bring to hght the influence of the solvent structure and the role of substrate interactions, etc As a result of this approach, the "composition" of oM.x m terms of the fundamental molecular constants becomes clear. With a view to use these molecular results to maxamum advantage, the derived results for ( \sigma MAX M) have been converted into those involving experimentally observable parameters lake Co, C 1, E N, etc Wherever possible, some of the earlier phenomenologlcal relations reported for ( \sigma MAX M), notably by Parsons, Damaskm and Frumkln, and Trasattl, are shown to have a certain molecular basis, vlz a simple two-state sate panty model.As a corollary to the hxerarcbacal modelling, \sigma MAX M and the potential corresponding to at (Emax) are shown to be constants independent of 0max or Corg for all models The lmphcatlon of our analysis f o r OmMa x with respect to that predicted by the generalized surface layer equation (which postulates Om~ and Ema x varlaUon with 0) is discussed in detail Finally we discuss an passing o M. and the electrosorptlon valency an this context.

Ultrafast and reversible multiblock formation by the SET-Nitroxide radical coupling reaction

The single electron transfer-nitroxide radical coupling (SET-NRC) reaction has been used to produce multiblock polymers with high molecular weights in under 3 min at 50◦C by coupling a difunctional telechelic polystyrene (Br-PSTY-Br)with a dinitroxide. The well known combination of dimethyl sulfoxide as solvent and Me6TREN as ligand facilitated the in situ disproportionation of CuIBr to the highly active nascent Cu0 species. This SET reaction allowed polymeric radicals to be rapidly formed from their corresponding halide end-groups. Trapping of these carbon-centred radicals at close to diffusion controlled rates by dinitroxides resulted in high-molecular-weight multiblock polymers. Our results showed that the disproportionation of CuI was critical in obtaining these ultrafast reactions, and confirmed that activation was primarily through Cu0. We took advantage of the reversibility of the NRC reaction at elevated temperatures to decouple the multiblock back to the original PSTY building block through capping the chain-ends with mono-functional nitroxides. These alkoxyamine end-groups were further exchanged with an alkyne mono-functional nitroxide (TEMPO–≡) and ‘clicked’ by a CuI-catalyzed azide/alkyne cycloaddition (CuAAC) reaction with N3–PSTY–N3 to reform the multiblocks. This final ‘click’ reaction, even after the consecutive decoupling and nitroxide-exchange reactions, still produced high molecular-weight multiblocks efficiently. These SET-NRC reactions would have ideal applications in re-usable plastics and possibly as self-healing materials.

Anisotropic gaussian beams

Anisotropic gaussian beams are obtained as exact solutions to the parabolic wave equation. These beams have a quadratic phase front whose principal radii of curvature are non-degenerate everywhere. It is shown that, for the lowest order beams, there exists a plane normal to the beam axis where the intensity distribution is rotationally symmetric about the beam axis. A possible application of these beams as normal modes of laser cavities with astigmatic mirrors is noted.

Assessment of quality defects in macadamia kernels using NIR spectroscopy

Spectral data were collected of intact and ground kernels using 3 instruments (using Si-PbS, Si, and InGaAs detectors), operating over different areas of the spectrum (between 400 and 2500 nm) and employing transmittance, interactance, and reflectance sample presentation strategies. Kernels were assessed on the basis of oil and water content, and with respect to the defect categories of insect damage, rancidity, discoloration, mould growth, germination, and decomposition. Predictive model performance statistics for oil content models were acceptable on all instruments (R2 > 0.98; RMSECV < 2.5%, which is similar to reference analysis error), although that for the instrument employing reflectance optics was inferior to models developed for the instruments employing transmission optics. The spectral positions for calibration coefficients were consistent with absorbance due to the third overtones of CH2 stretching. Calibration models for moisture content in ground samples were acceptable on all instruments (R2 > 0.97; RMSECV < 0.2%), whereas calibration models for intact kernels were relatively poor. Calibration coefficients were more highly weighted around 1360, 740 and 840 nm, consistent with absorbance due to overtones of O-H stretching and combination. Intact kernels with brown centres or rancidity could be discriminated from each other and from sound kernels using principal component analysis. Part kernels affected by insect damage, discoloration, mould growth, germination, and decomposition could be discriminated from sound kernels. However, discrimination among these defect categories was not distinct and could not be validated on an independent set. It is concluded that there is good potential for a low cost Si photodiode array instrument to be employed to identify some quality defects of intact macadamia kernels and to quantify oil and moisture content of kernels in the process laboratory and for oil content in-line. Further work is required to examine the robustness of predictive models across different populations, including growing districts, cultivars and times of harvest.

Functionally associated molecular genetic marker map construction in perennial ryegrass (Lolium perenne L.)

A molecular marker-based map of perennial ryegrass (Lolium perenne L.) has been constructed through the use of polymorphisms associated with expressed sequence tags (ESTs). A pair-cross between genotypes from a North African ecotype and the cultivar Aurora was used to generate a two-way pseudo-testcross population. A selection of 157 cDNAs assigned to eight different functional categories associated with agronomically important biological processes was used to detect polymorphic EST–RFLP loci in the F1(NA6 × AU6) population. A comprehensive set of EST–SSR markers was developed from the analysis of 14,767 unigenes, with 310 primer pairs showing efficient amplification and detecting 113 polymorphic loci. Two parental genetic maps were produced: the NA6 genetic map contains 88 EST–RFLP and 71 EST–SSR loci with a total map length of 963 cM, while the AU6 genetic map contains 67 EST–RFLP and 58 EST–SSR loci with a total map length of 757 cM. Bridging loci permitted the alignment of homologous chromosomes between the parental maps, and a sub-set of genomic DNA-derived SSRs was used to relate linkage groups to the perennial ryegrass reference map. Regions of segregation distortion were identified, in some instances in common with other perennial ryegrass maps. The EST-derived marker-based map provides the basis for in silico comparative genetic mapping, as well as the evaluation of co-location between QTLs and functionally associated genetic loci.

Structural Basis of Drug Resistance by Genetic Variants of HIV Type 1 Clade C Protease from India

Using computer modeling of three-dimensional structures and structural information available on the crystal structures of HIV-1 protease, we investigated the structural effects of mutations, in treatment-naive and treatment-exposed individuals from India and postulated mechanisms of resistance in clade C variants. A large number of models (14) have been generated by computational mutation of the available crystal structures of drug bound proteases. Localized energy minimization was carried out in and around the sites of mutation in order to optimize the geometry of interactions present. Most of the mutations result in structural differences at the flap that favors the semiopen state of the enzyme. Some of the mutations were also found to confer resistance by affecting the geometry of the active site. The E35D mutation affects the flap structure in clade B strains and E35N and E35K mutation, seen in our modeled strains, have a more profound effect. Common polymorphisms at positions 36 and 63 in clade C also affected flap structure. Apart from a few other residues Gln-58, Asn-83, Asn-88, and Gln-92 and their interactions are important for the transition from the closed to the open state. Development of protease inhibitors by structure-based design requires investigation of mechanisms operative for clade C to improve the efficacy of therapy.