The CD40-CD154 system in anti-infective host defense

Research in the past few years has documented significant advances in our understanding of the CD40-CD40 ligand (CD154) system in diverse immune functions. This system influences many T cell mediated inflammatory immune responses and effector functions, unmasking a previously unexpected role for CD40-CD154 in cell mediated immunity. Manipulation of CD154 in animal models of infection by the use of CD154-deficient mice or anti-CD154 antibodies has shown the importance of this system in the initiation of the inflammatory response, in the activation of antigen-presenting cells and in resistance to infections.     

Clinical associations of prenatal ischaemic white matter injury

Neuropathological examinations were carried out at necropsy on 274 cases of intrauterine death or neonatal death at or before three days after birth. Fifty six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review of the maternal case notes to ascertain antenatal clinical associations there was an increased incidence of intrauterine growth retardation, either based on birth weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1 to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine growth retardation and white matter damage remained after excluding fetuses with a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that chronic intrauterine hypoxia may be associated with damage to cerebral white matter among fetuses and infants who die. The relation between ischaemic white matter damage and cerebral palsy among survivors remains speculative.     

On-Line Shape recognition with incremental training using binary synaptic weights algorithm

Recognition of hand drawn shapes is beneficial in drawing packages and automated sketch entry in handheld computers. In this paper, we propose a new approach to on-line geometric shape recognition with incremental training function, which utilizes a heuristic function to reduce noise and a neural network for classification and on-line training. Instead of recognizing segments of a drawing and then performing syntactical analysis to match with a predefined shape, which is weak in terms of generalization and dealing with noise, we examine the shape as a whole. The main concept of the recognition method is derived from the fact that internal angles are very important in the perceived shape of outlines. Our application's aim is to recognize elliptic, rectangular, and triangular shapes in a way similar to human cognition of these shapes. Human beings recognize such basic shapes regardless of the variations in size, noise on the shape border, rotation and in the case of triangles, regardless of the type of the triangle. The key concept is that the neural network learns the relationships between the internal angles of a shape and its classification, therefore only a few training samples which represent the class of the shape are sufficient. Fast meremental training, which is performed on-line, is accomplished by the use of the Binary Synaptic Weights algorithm, a one pass, feedforward neural network training algorithm. Incremental training offers the advantage of adjusting the recognition capability of the system to the user's drawings. the results are very successful, such that the neural network correctly classified shapes that did not have any resemblance to the shapes in the initial training set.     

Catalytic properties of SrSn1−xSbxO3 in methanol oxidation

Ceramic model catalyst materials of general formula SrSn_1–x Sb _x O₃ are synthesised by solid state reaction. X-ray diffraction shows the materials to be single phase over the composition range 0 x0.085, with a second phase, identified as SrSb₂O₅, being produced at higher antimony doping levels. XPS, Auger electron spectroscopy and valence band photoemission show strong segregation of Sb to the surface of the material even within the single phase regime. The catalytic properties of the materials are examined using methanol oxidation as a test reaction. The activity and selectivity to formaldehyde production shown by these materials is found to be strongly correlated with the attainment of the bulk solubility limit of Sb in the SrSnO₃ perovskite host.     

The Role of Cholesterol on Triterpenoid Saponin-Induced Endolysosomal Escape of a Saporin-Based Immunotoxin

Cholesterol seems to play a central role in the augmentation of saporin-based immunotoxin (IT) cytotoxicity by triterpenoid saponins. Endolysosomal escape has been proposed as one mechanism for the saponin-mediated enhancement of targeted toxins. We investigated the effects of lipid depletion followed by repletion on Saponinum album (SA)-induced endolysosomal escape of Alexa Fluor labelled saporin and the saporin-based immunotoxin OKT10-SAP, directed against CD38, in Daudi lymphoma cells. Lipid deprived cells showed reduced SA-induced endolysosomal escape at two concentrations of SA, as determined by a flow cytometric method. The repletion of membrane cholesterol by low density lipoprotein (LDL) restored SA-induced endolysosomal escape at a concentration of 5 µg/mL SA but not at 1 µg/mL SA. When LDL was used to restore the cholesterol levels in lipid deprived cells, the SA augmentation of OKT10-SAP cytotoxicity was partially restored at 1 µg/mL SA and fully restored at 5 µg/mL SA. These results suggest that different mechanisms of action might be involved for the two different concentrations of SA and that endosomal escape may not be the main mechanism for the augmentation of saporin IT cytotoxicity by SA at the sub-lytic concentration of 1 µg/mL SA.     

Polyborazylene oxides

The reactions of various B-dichloro-N-triarylborazines with boiling N,N-dimethylformamide (DMF), and DMF in the presence of dimethylamine have been shown to give condensation polymers of the polyborazylene oxide type. The degrees of polymerisation range in individual cases from about 2–25. The presence of one ortho substituent in the N-aryl group causes the molecular weight to fall sharply, and polymerisation is completely inhibited in the presence of two ortho substituents. Reactions of several N-triarylborazines with boiling DMF also gave polyborazylene oxide-type polymers together with trimethylamine. The infra-red spectra, and thermal and hydrolytic stability of the polymers have been investigated.     

Effect of increasing the salience of message ambiguities on kindergartners' evaluations of communicative success and message adequacy.

Previous research has shown that kindergarten children often appear uncertain or confused when they try to execute inadequate instructions but then go on to indicate that they had succeeded in doing what the instructor intended and that the instructions had been adequate. The present study was conducted with 72 kindergartners to test this research. Results confirm these findings and demonstrate that Ss' positive evaluations of inadequate messages were not due to forgetting their initial uncertainty. Extra emphasis on the ambiguous nature of the instructions helped Ss realize that they might not have succeeded in doing what the instructor intended them to, but it did not help them realize that the instructions had been inadequate. In contrast, emphasizing exactly what they were to achieve did not help them recognize either their possible failure in the task or the inadequacy of the instructions. Ss' performance resulted from a poor understanding of message quality and the role it plays in determining the success or failure of a communication. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion

Mucus hypersecretion and plugging of lower respiratory tract airways contributes to the morbidity and mortality associated with asthma. Interleukin (IL)-4 plays a putative role in some forms of asthma. Thus, transgenic mice that overexpress murine IL-4 selectively within the lung were used to study the effect of IL-4 on mucus glycoprotein gene expression and mucin release. Histologic examination of lung sections from IL-4 mice revealed that nonciliated epithelial cells from conducting airways were hypertrophic, due at least in part to the accumulation of mucus glycoprotein. The cytoplasm of these cells stained positively for glycoproteins using mucicarmine, alcian blue (AB), and periodic acid-Schiff (PAS). Ciliated cells were also enlarged but did not show any mucin-specific staining. Inclusion granules typically found in nonciliated (Clara) cells of control mice were absent in the IL-4 transgenic mice. Northern blot analysis of total RNA from lung tissue revealed that the expression of the MUC5AC, but not MUC2, mucin gene was distinctly upgraded in IL-4 transgenic mice compared to transgene-negative controls. In addition, a 5- to 10-fold increase in AB- and PAS-positive material was found in lavage fluid from IL-4 overexpressing mice compared to transgene-negative controls. Thus, the overexpression of IL-4 locally within the lung enhances mucus glycoprotein synthesis by altering gene expression, results in the accumulation of mucus glycoprotein in nonciliated epithelial cells, and induces the release of mucus into the airway lumen. We therefore hypothesize that the overproduction of mucus seen in some patients with asthma may be a direct result of the action of IL-4 within the inflamed lung.     

Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells

Murine Lyme borreliosis is characterized by arthritis and carditis that are most severe at 2 to 3 wk, then regress during the course of persistent infection. Borrelia burgdorferi-specific Abs and CD4+ T cells have been implicated in the resolution phase of arthritis. Therefore, MHC class II transactivator (CIITA)-deficient mice that do not express conventional class II molecules and lack the normal CD4 repertoire were used to investigate the role of MHC class II-mediated responses in Lyme disease. The development of arthritis and carditis, and the resolution of arthritis, were similar in CIITA-deficient and control C57/BL6 mice. In contrast, the resolution of carditis was delayed in CIITA-deficient animals compared with controls. Moreover, CIITA-deficient mice developed B. burgdorferi-specific IgG2b Abs, and sera from these animals passively protected naive C3H/HeN mice from challenge inoculation and cleared B. burgdorferi from 2 day-infected C.B.17 SCID mice. These data suggest that CD4+ T cells and MHC class II-mediated responses are not required for the generation of protective Abs or the regression of arthritis, but may be important in the resolution of Lyme carditis in mice.