A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein

Post mortem biochemical staging of Alzheimer’s disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205.

Analysis of human chorionic gonadotropin-monoclonal antibody interaction in BIAcore

Kinetic studies of macromolecular ligand-ligate interaction have generated ample interest since the advent of plasmon resonance based instruments like BIAcore. Most of the studies reported in literature assume a simple 1 : 1 Langmuir binding and complete reversibility of the system. However we observed that in a high affinity antigen-antibody system [human chorionic gonadotropin-monoclonal antibody (hCG-mAb)] dissociation is insignificant and the sensogram data cannot be used to measure the equilibrium and kinetic parameters. At low concentrations of mAb the complete sensogram could be fitted to a single exponential. Interestingly we found that at higher mAb concentrations, the binding data did not conform to a simple bimolecular model. Instead, the data fitted a two-step model, which may be because of surface heterogeneity of affinity sites. In this paper, we report on the global fit of the sensograms. We have developed a method by which a single two-minute sensogram can be used in high affinity systems to measure the association rate constant of the reaction and the functional capacity of the ligand (hCG) immobilized on the chip. We provide a rational explanation for the discrepancies generally observed in most of the BIAcore sensograms

Application of artificial intelligence for the assessment of the status of power transformers

The Dissolved Gas Analysis (DGA) a non destructive test procedure, has been in vogue for a long time now, for assessing the status of power and related transformers in service. An early indication of likely internal faults that may exist in Transformers has been seen to be revealed, to a reasonable degree of accuracy by the DGA. The data acquisition and subsequent analysis needs an expert in the concerned area to accurately assess the condition of the equipment. Since the presence of the expert is not always guaranteed, it is incumbent on the part of the power utilities to requisition a well planned and reliable artificial expert system to replace, at least in part, an expert. This paper presents the application of Ordered Ant Mner (OAM) classifier for the prediction of involved fault. Secondly, the paper also attempts to estimate the remaining life of the power transformer as an extension to the elapsed life estimation method suggested in the literature.

A CD8(+) T cell clone specific for antigen also recognizes peptidomimics present in anti-idiotypic antibody: Implications for T cell memory

The relay hypothesis [R. Nayak, S. Mitra-Kaushik, M.S. Shaila, Perpetuation of immunological memory: a relay hypothesis, Immunology 102 (2001) 387-395] was earlier proposed to explain perpetuation of immunological memory without requiring long lived memory cells or persisting antigen. This hypothesis envisaged cycles of interaction and proliferation of complementary idiotypic B cells (Burnet cells) and anti-idiotypic B cells (Jerne cells) as the primary reason for perpetuation of immunological memory. The presence of pepti-domimics of antigen in anti-idiotypic antibody and their presentation to antigen specific T cells was postulated to be primary reason for perpetuation of T cell memory. Using a viral hemagglutinin as a model, in this work, we demonstrate the presence of peptidomimics in the variable region of ail anti-idiotypic antibody capable of functionally mimicking the antigen derived peptides. A CD8(+) CTL clone was generated against the hemagglutinin protein which specifically responds to either peptidomimic synthesizing cells or peptidomimic pulsed antigen presenting cells. Thus, it appears reasonable that a population of activated antigen specific T cells is maintained in the body by presentation of peptidomimic through Jerne cells and other antigen presenting cells long after immunization. (C) 2007 Elsevier Inc. All rights reserved.

Classification of Indian meteorological stations using cluster and fuzzy cluster analysis, and Kohonen artificial neural networks

The present study deals with the application of cluster analysis, Fuzzy Cluster Analysis (FCA) and Kohonen Artificial Neural Networks (KANN) methods for classification of 159 meteorological stations in India into meteorologically homogeneous groups. Eight parameters, namely latitude, longitude, elevation, average temperature, humidity, wind speed, sunshine hours and solar radiation, are considered as the classification criteria for grouping. The optimal number of groups is determined as 14 based on the Davies-Bouldin index approach. It is observed that the FCA approach performed better than the other two methodologies for the present study.

The Edge of Danger: artificial lighting and the dialectics of domestic occupation in Philip Johnson's Glass and Guest Houses

In the first half of the twentieth century the dematerializing of boundaries between enclosure and exposure problematized traditional acts of “occupation” and understandings of the domestic environment. As a space of escalating technological control, the modern domestic interior offered new potential to re-define the meaning and means of habitation. This shift is clearly expressed in the transformation of electric lighting technology and applications for the modern interior in the mid-twentieth century. Addressing these issues, this paper examines the critical role of electric lighting in regulating and framing both the public and private occupation of Philip Johnson’s New Canaan estate. Exploring the dialectically paired transparent Glass House and opaque Guest House (both 1949), this study illustrates how Johnson employed artificial light to control the visual environment of the estate as well as to aestheticize the performance of domestic space. Looking closely at the use of artificial light to create emotive effects as well as to intensify the experience of occupation, this revisiting of the iconic Glass House and lesser-known Guest House provides a more complex understanding of Johnson’s work and the means with which he inhabited his own architecture. Calling attention to the importance of Johnson serving as both architect and client, and his particular interest in exploring the new potential of architectural lighting in this period, this paper investigates Johnson’s use of electric light to support architectural narratives, maintain visual order and control, and to suit the nuanced desires of domestic occupation.

Investigation of true remnant polarization response in heterostructured artificial biferroics

Epitaxial bilayered thin films composed of ferromagnetic La0.6Sr0.4MnO3 and ferroelectric 0.7Pb (Mg1/3Nb2/3)O3-0.3(PbTiO3) were fabricated on LaAlO3 (100) substrates by pulsed laser ablation. Ferroelectric, ferromagnetic and magneto-dielectric characterizations performed earlier indicated the possible existence of strain-mediated magneto-electric coupling in these biferroic heterostructures. In order to investigate their true remnant polarization characteristics, usable in devices, room-temperature polarization versus electric field, positive-up negative-down (PUND) pulse polarization studies and remnant hysteresis measurements were carried out. The PUND and remnant hysteresis measurements revealed the significant contribution of the non-remnant component in the observed polarization hysteresis response of these heterostructures. (C) 2010 Published by Elsevier Ltd

Prediction of swelling pressure of soil using artificial intelligence techniques

The swelling pressure of soil depends upon various soil parameters such as mineralogy, clay content, Atterberg's limits, dry density, moisture content, initial degree of saturation, etc. along with structural and environmental factors. It is very difficult to model and analyze swelling pressure effectively taking all the above aspects into consideration. Various statistical/empirical methods have been attempted to predict the swelling pressure based on index properties of soil. In this paper, the computational intelligence techniques artificial neural network and support vector machine have been used to develop models based on the set of available experimental results to predict swelling pressure from the inputs; natural moisture content, dry density, liquid limit, plasticity index, and clay fraction. The generalization of the model to new set of data other than the training set of data is discussed which is required for successful application of a model. A detailed study of the relative performance of the computational intelligence techniques has been carried out based on different statistical performance criteria.

Prediction of swelling pressure of soil using artificial intelligence techniques

The swelling pressure of soil depends upon various soil parameters such as mineralogy, clay content, Atterberg's limits, dry density, moisture content, initial degree of saturation, etc. along with structural and environmental factors. It is very difficult to model and analyze swelling pressure effectively taking all the above aspects into consideration. Various statistical/empirical methods have been attempted to predict the swelling pressure based on index properties of soil. In this paper, the computational intelligence techniques artificial neural network and support vector machine have been used to develop models based on the set of available experimental results to predict swelling pressure from the inputs; natural moisture content, dry density, liquid limit, plasticity index, and clay fraction. The generalization of the model to new set of data other than the training set of data is discussed which is required for successful application of a model. A detailed study of the relative performance of the computational intelligence techniques has been carried out based on different statistical performance criteria.

A new ELISA plate based microtiter well assay for mycobacterial topoisomerase I for the direct screening of enzyme inhibitory monoclonal antibody supernatants

Antigen specific monoclonal antibodies present in crude hybridoma supernatants are normally screened by ELISA on plates coated with the relevant antigen. Screening for inhibitory monoclonals to enzymes would require the evaluation of purified antibodies or antibody containing supernatants for their inhibition of enzyme activity in a separate assay. However, screening for inhibitory antibodies against DNA transacting enzymes such as topoisomerase I (topo I) cannot be done using hybridoma supernatants due to the presence of nucleases in tissue culture media containing foetal calf serum which degrade the DNA substrates upon addition. We have developed a simple and rapid screening procedure for the identification of clones that secrete inhibitory antibodies against mycobacterial topo I using 96 well ELISA microtiter plates. The principle of the method is the selective capture of monoclonal antibodies from crude hybridoma supernatants by topo I that is tethered to the plate through the use of plate-bound polyclonal anti-topo I antibodies. This step allows the nucleases present in the medium to be washed off leaving the inhibitor bound to the tethered enzyme. The inhibitory activity of the captured antibody is assessed by performing an in situ DNA relaxation assay by the addition of supercoiled DNA substrate directly to the microtiter well followed by the analysis of the reaction products by agarose gel electrophoresis. The validity of this method was confirmed by purification of the identified inhibitory antibody and its evaluation in a DNA relaxation assay. Elimination of all enzyme-inhibitory constituents of the culture medium from the well in which the inhibitory antibody is bound to the tethered enzyme may make this method broadly applicable to enzymes such as DNA gyrases, restriction enzymes and other DNA transaction enzymes. Further, the method is simple and avoids the need of prior antibody purification for testing its inhibitory activity. (C) 2010 Elsevier B.V. All rights reserved.

Multiple contour extraction from graylevel images using an artificial neural network

For active contour modeling (ACM), we propose a novel self-organizing map (SOM)-based approach, called the batch-SOM (BSOM), that attempts to integrate the advantages of SOM- and snake-based ACMs in order to extract the desired contours from images. We employ feature points, in the form of ail edge-map (as obtained from a standard edge-detection operation), to guide the contour (as in the case of SOM-based ACMs) along with the gradient and intensity variations in a local region to ensure that the contour does not "leak" into the object boundary in case of faulty feature points (weak or broken edges). In contrast with the snake-based ACMs, however, we do not use an explicit energy functional (based on gradient or intensity) for controlling the contour movement. We extend the BSOM to handle extraction of contours of multiple objects, by splitting a single contour into as many subcontours as the objects in the image. The BSOM and its extended version are tested on synthetic binary and gray-level images with both single and multiple objects. We also demonstrate the efficacy of the BSOM on images of objects having both convex and nonconvex boundaries. The results demonstrate the superiority of the BSOM over others. Finally, we analyze the limitations of the BSOM.

Passive immunization with an antibody to the beta-subunit of ovine luteinizing hormone as a method of early abortion--a feasibility study in monkeys (Macaca radiata)

Antiserum to the beta-subunit of ovine luteinizing hormone (oLH-beta) raised in monkeys (Macaca radiata) has been tested by a variety of criteria both in vivo and in vitro to establish its ability to neutralize oLH, hLH, and human chorionic gonadotropin (hCG). Passive administration of this antiserum caused inhibition of ovulation and termination of pregnancy in recipient monkeys as indicated by premature vaginal bleeding and a significant reduction in serum progesterone and estrogen levels. The results suggest that antiserum raised in monkeys against oLH-beta can neutralize monkey LH as well as monkey CG.