Hapten synthesis and antibody production for the development of a melamine immunoassay

The incorporation of melamine into food products is banned but its misuse has been widely reported in both animal feeds and food. The development of a rapid screening immunoassay for monitoring of the substance is an urgent requirement. Two haptens of melamine were synthesized by introducing spacer arms of different lengths and structures on the triazine ring of the analyte molecular structure. 6-Aminocaproic acid and 3-mercaptopropionic acid were reacted with 2-chloro-4,6-diamino-1,3,5-triazine (CAAT) to produce hapten 1[3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylamino) hexanoic acid] and hapten 2[3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylthio) propanoic acid]. respectively. The molecular structures of the two haptens were identified by I H nuclear magnetic resonance spectrometry, mass spectrometry and infrared spectrometry. An immunogen was prepared by coupling hapten 1 to bovine serum albumin (BSA). Two plate coating antigens were prepared by coupling both haptens to egg ovalbumin (OVA). A competitive indirect enzyme-linked immunosorbent assay (ciELISA) was developed to evaluate homogeneous and heterogeneous assay formats. The results showed that polyclonal antibodies with high titers were obtained, and the heterogeneous immunoassay format demonstrated a better performance with an IC50 of 70.6 ng mL(-1), a LOD of 2.6 ng mL(-1) and a LOQ of 7.6 ng mL(-1). Except for cyromazine, no obvious cross-reactivity to common compounds was found. The data showed that the hapten synthesis was successful and the resultant antisera could be used in an immunoassay for the rapid and sensitive detection of this banned chemical. (C) 2010 Elsevier B.V. All rights reserved.

Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy

A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol beta, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol beta protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol beta protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta-expressing cells. Consistent with previous studies, Pol beta-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol beta. They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin treatment. Oncogene (2010) 29, 463-468; doi:10.1038/onc.2009.327; published online 19 October 2009

Children’s attributions of belief to humans and God: cross-cultural evidence

The capacity to attribute beliefs to others in order to understand action is one of the mainstays of human cognition. Yet it is debatable whether children attribute beliefs in the same way to all agents. In this paper, we present the results of a false-belief task concerning humans and God run with a sample of Maya children aged 4–7, and place them in the context of several psychological theories of cognitive development. Children were found to attribute beliefs in different ways to humans and God. The evidence also speaks to the debate concerning the universality and uniformity of the development of folk-psychological reasoning.

Echolocation signal structure in the Megachiropteran bat Rousettus aegyptiacus Geoffroy 1810

Rousettus aegyptiacus Geoffroy 1810 is a member of the only genus of Megachiropteran bats to use vocal echolocation, but the structure of its brief, click-like signal is poorly described. Although thought to have a simple echolocation system compared to that of Microchiroptera, R. aegyptiacus is capable of good obstacle avoidance using its impulse sonar. The energy content of the signal was at least an order of magnitude smaller than in Microchiropteran bats and dolphins (approximately 4 X 10(-8) J m(-2)). Measurement of the duration, amplitude and peak frequency demonstrate that the signals of this animal are broadly similar in structure and duration to those of dolphins. Gabor functions were used to model signals and to estimate signal parameters, and the quality of the Gabor function fit to the early part of the signal demonstrates that the echolocation signals of R. aegyptiacus match the minimum spectral spread for their duration and amplitude and are thus well matched to its best hearing sensitivity. However, the low energy content of the signals and short duration should make returning echoes difficult to detect. The performance of R. aegyptincus in obstacle avoidance experiments using echolocation therefore remains something of a conundrum.

Eclipsing Binary Science via the Merging of Transit and Doppler Exoplanet Survey Data—A Case Study with the MARVELS Pilot Project and SuperWASP

Exoplanet transit and Doppler surveys discover many binary stars during their operation that can be used to conduct a variety of ancillary science. Specifically, eclipsing binary stars can be used to study the stellar mass-radius relationship and to test predictions of theoretical stellar evolution models. By cross-referencing 24 binary stars found in the MARVELS Pilot Project with SuperWASP photometry, we find two new eclipsing binaries, TYC 0272-00458-1 and TYC 1422-01328-1, which we use as case studies to develop a general approach to eclipsing binaries in survey data. TYC 0272-00458-1 is a single-lined spectroscopic binary for which we calculate a mass of the secondary and radii for both components using reasonable constraints on the primary mass through several different techniques. For a primary mass of M 1 = 0.92 ± 0.1 M sun, we find M 2 = 0.610 ± 0.036 M sun, R 1 = 0.932 ± 0.076 R sun, and R 2 = 0.559 ± 0.102 R sun, and find that both stars have masses and radii consistent with model predictions. TYC 1422-01328-1 is a triple-component system for which we can directly measure the masses and radii of the eclipsing pair. We find that the eclipsing pair consists of an evolved primary star (M 1 = 1.163 ± 0.034 M sun, R 1 = 2.063 ± 0.058 R sun) and a G-type dwarf secondary (M 2 = 0.905 ± 0.067 M sun, R 2 = 0.887 ± 0.037 R sun). We provide the framework necessary to apply this analysis to much larger data sets.

The Sound of Becoming: Moving Towards a Virtual Music

In 1985 Jacques Attali proposed a new modality for music. He suggests that there be “not a new music, but a new way of making music... a radically new form of the insertion of music into communication” (Attali 134). What Attali foretold has become a firm reality in contemporary musical practice. One has only to look at any current musical activity to encounter work that relies heavily on real-time interaction and dynamic generation and/or modification of materials. But why is this ontologically different ‘mode of essentially interactive and transformative existence’ (Ziarek 195), this ‘new way of making music’, so attractive to contemporary artists? What is motivating artists to abandon a production model in favor of a model of real-time interactive exploration? I will argue that at the foundation of this new artistic ontology lies Deleuze’s concept of the virtual. It is a recognition of the virtual power of music, that music making can be an act of invention, a process where one can discover something never before experienced.

Semiotics, Presence and the Sublime in the Work of Alvin Lucier

Alvin Lucier, in his uncompromising exploration into the artistic potential of acoustic phenomena, has developed a body of work that remains highly original and hugely influential across many disciplines. His seminal works such as I am sitting in a room and Music for Solo Performer foreshadowed ways of approaching sound that are in common use among electro-acoustic composers, installation artists, as well as in commercial products. Lucier, despite his far reaching influence, is and has always been a composer, and his explorations of acoustics have been singularly focused on the development of a rich body of music. In this article, I investigate Lucier’s unique approach and attitude towards acoustics and aspire to enumerate important aesthetic developments he has made in creating music through the exploration of acoustic phenomena. In particular, this article seeks to investigate the role of semiotics in Lucier’s work, commenting on the pre-linguistic nature of Lucier’s approach to acoustic phenomenon. Here as well, an exploration of Lucier’s musical materials takes place, focusing on his instrumental compositions, specifically Diamonds for One, Two or Three Orchestras, where instruments are used as catalysts to generate in real-time acoustic phenomenon which interact to produce a rich yet intimate world of sound. Finally, Lucier’s approach to semiotics and real-time generation of music is viewed through a sublime aesthetic provoking questions regarding issues of presence and the now.

Portfolio of Compositions investigating ensemble improvisation, distributed and real-time scoring, and multi-nodal input and output

This output is a collection of compositions which explore issues of ensemble improvisation, ensemble management and orchestration, real-time and distributed scoring, multi-nodal inputs and outputs, and animated and graphic notation. Compositions include: Activities I; tutti, duet, trio, solo, quartet; Lewitt Notations I; Webwork I; and Sometimes I feel the space between people (voices) in terms of tempos. These compositions are presented in computer animated scores which are synchronized through the network and subject to real-time modification and control. They can be performed by ensembles distributed over large physical spaces connected by the network. The scores for these compositions include software which displays the animations to the performers, software to structure and disseminate score events, and triggering software that allows the control of a performance to be distributed. Scores can also include live electronics which are coordinated with graphic events.

The Science of Religious Beliefs

Why have humans, throughout history and across cultures, shown a strong tendency to believe in the existence of superhuman intentional agents and attached this belief to notions of morality, misfortune, and the creation of the world? The answer emerging from the cognitive science of religion appears to be that explicit beliefs are informed and constrained by the natural and cross-culturally recurrent operation of implicit cognitive systems. Successful god concepts resonate with the expectations of these implicit systems but also have attention-demanding and inferentially-rich properties that allow their integration into various areas of human concern. Theological concepts may deviate from these natural cognitive moorings but require special cultural scaffolding, such as Whitehouse's two Modes of Religiosity, to do so and constitute additions to, rather than replacements of the religious beliefs supported by implicit cognitive systems.

Vascular Endothelial Cell Growth–Activated XBP1 Splicing in Endothelial Cells Is Crucial for Angiogenesis

BACKGROUND - : Vascular endothelial cell growth factor plays a pivotal role in angiogenesis via regulating endothelial cell proliferation. The X-box binding protein 1 (XBP1) is believed to be a signal transducer in the endoplasmic reticulum stress response. It is unknown whether there is crosstalk between vascular endothelial cell growth factor signaling and XBP1 pathway. 

METHODS AND RESULTS - : We found that vascular endothelial cell growth factor induced the kinase insert domain receptor internalization and interaction through C-terminal domain with the unspliced XBP1 and the inositol requiring enzyme 1 α in the endoplasmic reticulum, leading to inositol requiring enzyme 1 α phosphorylation and XBP1 mRNA splicing, which was abolished by siRNA-mediated knockdown of kinase insert domain receptor. Spliced XBP1 regulated endothelial cell proliferation in a PI3K/Akt/GSK3β/β- catenin/E2F2-dependent manner and modulated the cell size increase in a PI3K/Akt/GSK3β/β-catenin/E2F2-independent manner. Knockdown of XBP1 or inositol requiring enzyme 1 α decreased endothelial cell proliferation via suppression of Akt/GSK3β phosphorylation, β-catenin nuclear translocation, and E2F2 expression. Endothelial cell-specific knockout of XBP1 (XBP1ecko) in mice retarded the retinal vasculogenesis in the first 2 postnatal weeks and impaired the angiogenesis triggered by ischemia. Reconstitution of XBP1 by Ad-XBP1s gene transfer significantly improved angiogenesis in ischemic tissue in XBP1ecko mice. Transplantation of bone marrow from wild-type o XBP1ecko mice could also slightly improve the foot blood reperfusion in ischemic XBP1ecko mice. 

CONCLUSIONS - : These results suggest that XBP1 can function via growth factor signaling pathways to regulate endothelial proliferation and angiogenesis. 

Protein kinase C{delta} deficiency accelerates neointimal lesions of mouse injured artery involving delayed reendothelialization and vasohibin-1 accumulation

To use protein kinase C (PKC) d-knockout mice to investigate the role of PKCd in lesion development and to understand the underlying mechanism of the vascular disease.