Phase-sensitive spatially-modulated surface plasmon resonance polarimetry for detection of biomolecular interactions

We here describe a scheme of spatially modulated surface plasmon resonance (SPR) polarimetry that enables to combine ultra-high phase sensitivity with good signal-to-noise background. The proposed approach uses spatial modulation of s-polarized component by birefringent elements and the extraction of phase-polarization information by Fourier-transform methods. This scheme was tested for monitoring the interactions between an antibody and its biological partner. Our experimental data, collected by amplitude-sensitive and phase-sensitive polarimetry demonstrate that the latter scheme provides at least one order of magnitude improvement in terms of detection limit.     

The significance of colour velocity and spectral Doppler ultrasound in the differentiation of liver tumours

BACKGROUND: The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME-1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been observed in many ACAs and reportedly is absent in MM. METHODS: In this study, immunostaining was performed on formalin fixed, paraffin embedded cell blocks from effusions or fine-needle aspirations using the avidin-biotin-peroxidase method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9, HBME-1, and TM. RESULTS: Anti-CA 19-9 stained only 1 of the 37 cases of MM tested (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38 cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of 36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%). CONCLUSIONS: CA 19-9 has utility as part of an immunocytochemical panel for distinguishing ACA from MM, because a positive staining reaction would make the diagnosis of MM unlikely. Although HBME-1 and TM can identify MM positively, each frequently is detected in ACA, thus limiting the utility of these antibodies in cytologic specimens.     

Ultrastructural evidence for intra- and extranuclear projections of GABAergic neurons of the suprachiasmatic nucleus

GABAergic projections of the suprachiasmatic nucleus (SCN) were demonstrated in a double-labelling ultrastructural study which visualised the efferents of the SCN by PHA-L tracing, diaminobenzidine (DAB) immunocytochemistry, and GABA with immunogold postembedding staining. The results show a strong contralateral projection of the SCN that is partly GABA-containing. In addition, ipsilateral SCN projections to the dorsomedial hypothalamus and periventricular part of the paraventricular nucleus and sub-paraventricular nucleus were shown to contain GABA. The present results indicate that the SCN may utilize this inhibitory neurotransmitter to regulate and organize its own circadian rhythm as well as using GABA to transmit its diurnal information to other regions of the brain.     

A developmental study of the acquisition of Russian colour terms

We report a study of the acquisition of colour terms by Russian children which had two main aims: first, to test Berlin & Kay's (1969) theory of colour universals using acquisition order as a measure of basicness; and secondly, to see if the two BLUE terms of Russian are genuinely basic. Two hundred children aged from three to six-years-old were tested on three colour-tasks--colour term listing, colour term production and colour term comprehension. To a reasonable approximation, the order of colour term acquisition was in accord with Berlin & Kay's theory, but the data are also consistent with the weaker claim that primary terms tend to be learned before derived terms. On balance the data were consistent with Russian exceptionally, having an extra term for the BLUE region. But, the two BLUE terms--goluboj 'light blue' and sinij 'dark blue'--were confused more often than other pairs of terms even by the five- to six-year-old sample.     

Sources of interracial variation in bone mineral density

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)     

Speculative Behaviour in Immature Real Estate Markets, Lessons of the 1997 Asia Financial Crisis

This article investigates speculative behaviour and focuses on developer and banker behaviour in Asian real estate markets at the time of the 1997 Asia financial crisis. Over-optimism and over-investment are exacerbated when the financial infrastructure is incomplete and real estate markets are immature. The article identifies improvements in the real estate market infrastructure needed to lower the amplitude and cost of future episodes of volatility.     

Transparent optical packet switching: network architecture anddemonstrators in the KEOPS project

This paper reviews the work carried out in the ACTS KEOPS (Keys to Optical Packet Switching) project, describing the results obtained to date. The main objective of the project is the definition, development, and assessment of optical packet switching and routing networks, capable of providing transparency to the payload bit rate, using optical packets of fixed duration and low bit rate headers in order to enable easier processing at the network/node interfaces. The feasibility of the KEOPS concept is assessed by modeling, laboratory experiments, and testbed implementation of optical packet switching nodes and network/node interfacing blocks, including a fully equipped demonstrator. The demonstration relies on advanced optoelectronic components, developed within the project, which are described     

Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines

Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vaccines. Here, we describe a mucoadhesive patch made of a layer-by-layer assembly of polysaccharides, chitosan, and hyaluronic acid. The mucoadhesive patch was covered by adjuvanted nanoparticles carrying viral proteins. We showed that the nanoparticles effectively cross the outer layers of the sublingual mucosa to reach the epithelium. Furthermore, the encapsulated adjuvants, 3M-052 and mifamurtide, targeting toll-like receptor (TLR) 7/8 and nucleotide-binding oligomerization domain-2 (NOD2), respectively, remain fully active after encapsulation into nanoparticles and exhibit a cytokine/chemokine signature similar to the mucosal gold-standard adjuvant, the cholera toxin. However, the particulate adjuvants induced more moderate levels of proinflammatory interleukin (IL)-6 and keratinocyte chemoattractant (KC), suggesting a controlled activation of the innate immune response.     

In Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators

ABCB11 is responsible for biliary bile acid secretion at the canalicular membrane of hepatocytes. Variations in the ABCB11 gene cause a spectrum of rare liver diseases. The most severe form is progressive familial intrahepatic cholestasis type 2 (PFIC2). Current medical treatments have limited efficacy. Here, we report the in vitro study of Abcb11 missense variants identified in PFIC2 patients and their functional rescue using cystic fibrosis transmembrane conductance regulator potentiators. Three ABCB11 disease-causing variations identified in PFIC2 patients (i.e., A257V, T463I and G562D) were reproduced in a plasmid encoding an Abcb11-green fluorescent protein. After transfection, the expression and localization of the variants were studied in HepG2 cells. Taurocholate transport activity and the effect of potentiators were studied in Madin–Darby canine kidney (MDCK) clones coexpressing Abcb11 and the sodium taurocholate cotransporting polypeptide (Ntcp/Slc10A1). As predicted using three-dimensional structure analysis, the three variants were expressed at the canalicular membrane but showed a defective function. Ivacaftor, GLP1837, SBC040 and SBC219 potentiators increased the bile acid transport of A257V and T463I and to a lesser extent, of G562D Abcb11 missense variants. In addition, a synergic effect was observed when ivacaftor was combined with SBC040 or SBC219. Such potentiators could represent new pharmacological approaches for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the function of the transporter.     

Nitric Oxide Metabolic Pathway in Drought-Stressed Nodules of Faba Bean (Vicia faba L.)

Drought is an environmental stress that strongly impacts plants. It affects all stages of growth and induces profound disturbances that influence all cellular functions. Legumes can establish a symbiosis with Rhizobium-type bacteria, whose function is to fix atmospheric nitrogen in organs called nodules and to meet plant nitrogen needs. Symbiotic nitrogen fixation (SNF) is particularly sensitive to drought. We raised the hypothesis that, in drought-stressed nodules, SNF inhibition is partly correlated to hypoxia resulting from nodule structure compaction and an increased O₂ diffusion barrier, and that the nodule energy regeneration involves phytoglobin–nitric oxide (Pgb–NO) respiration. To test this hypothesis, we subjected faba bean (Vicia faba L.) plants nodulated with a Rhizobium laguerreae strain to either drought or osmotic stress. We monitored the N₂-fixation activity, the energy state (ATP/ADP ratio), the expression of hypoxia marker genes (alcohol dehydrogenase and alanine aminotransferase), and the functioning of the Pgb–NO respiration in the nodules. The collected data confirmed our hypothesis and showed that (1) drought-stressed nodules were subject to more intense hypoxia than control nodules and (2) NO production increased and contributed via Pgb–NO respiration to the maintenance of the energy state of drought-stressed nodules.