The ratio of diffuse to mature beta/A4 deposits in Alzheimer's disease varies in cases with and without pronounced congophilic angiopathy

The density of diffuse, primitive, classic and compact beta/A4 deposits was estimated in the cortex and hippocampus in Alzheimer's disease (AD) cases with and without pronounced congophilic angiopathy (CA). The total density of beta/A4 deposits in a given brain region was similar in cases with and without CA. Significantly fewer diffuse deposits and more primitive/classic deposits were found in the cases with CA. The densities of the primitive, classic and compact deposits were positively correlated in the cases without CA. However, no correlations were observed between the density of the mature subtypes and the diffuse deposits in these cases. In the cases with CA, the density of the primitive deposits was positively correlated with the diffuse but not with the classic deposits. The data suggest that the mature beta/A4 deposits are derived from the diffuse deposits and that the presence of pronounced CA enhances their formation.

Degeneration of cortical neurons associated with diffuse beta-amyloid (Abeta) deposits in Alzheimer’s disease

The frequency of morphological abnormalities in neuronal perikarya which were in contact with diffuse beta-amyloid (Abeta) deposits in patients with Alzheimer’s disease (AD) was compared with neurons located adjacent to the deposits. Morphological abnormalities were also studied in elderly, non-demented (ND) cases with and without diffuse Abeta deposits. In AD and ND cases with Abeta deposits, an increased proportion of neurons in contact with diffuse deposits exhibited at least one abnormality compared with neurons located adjacent to the deposits. Neurons in contact with diffuse deposits exhibited a greater frequency of abnormalities of shape, nuclei, nissl substance and had a higher frequency of cytoplasmic vacuoles compared with adjacent neurons. A greater frequency of abnormalities of shape, nissl substance and in the frequency of displaced nuclei were also observed in neurons adjacent to diffuse deposits in AD compared with ND cases. With the exception of absent nuclei, morphological abnormalities adjacent to diffuse deposits in ND cases were similar to those of ND cases without Abeta deposits. These results suggest that neuronal degeneration is associated with the earliest stages of Abeta deposit formation and is not specifically related to the formation of mature senile plaques.

Sun and sky:does human vision assume a mixture of point and diffuse illumination when interpreting shape-from-shading?

People readily perceive smooth luminance variations as being due to the shading produced by undulations of a 3-D surface (shape-from-shading). In doing so, the visual system must simultaneously estimate the shape of the surface and the nature of the illumination. Remarkably, shape-from-shading operates even when both these properties are unknown and neither can be estimated directly from the image. In such circumstances humans are thought to adopt a default illumination model. A widely held view is that the default illuminant is a point source located above the observer's head. However, some have argued instead that the default illuminant is a diffuse source. We now present evidence that humans may adopt a flexible illumination model that includes both diffuse and point source elements. Our model estimates a direction for the point source and then weights the contribution of this source according to a bias function. For most people the preferred illuminant direction is overhead with a strong diffuse component.

Spatial relationships between diffuse prion protein deposits and neuronal perikarya in variant Creutzfeldt-Jakob disease

Two morphological types of prion protein (PrPsc) deposit occur in the cerebral cortex of cases of variant Creutzfeldt-Jakob disease (vCJD), viz., diffuse and florid deposits. The objective of this study was to determine whether diffuse-type PrPsc deposits in areas of the cerebral cortex in six cases of the variant form of CJD (vCJD) were spatially correlated with neurons and whether diffuse deposit size was related to the number of adjacent neurons contributing PrPsc. In cortical gyri, density of surviving neurons was 5.38-12.15 per 50 × 200 µm sample field, neurons being distributed randomly, regularly or were clustered relative to the pia mater. Density of neurons embedded within diffuse deposits, however, was three to eight times their overall density in the section. In addition, diffuse deposit area was positively correlated with the number of embedded neurons. The frequency distribution of diffuse deposits with 0, 1, 2, 3, …, n, embedded neurons did not deviate from a Poisson distribution. These results suggest: (1) diffuse deposits in vCJD develop in situ as a result of the formation of PrPsc in relation to clusters of neurons, (2) size of a diffuse deposit is determined by the number of adjacent neurons which develop PrPsc, and (3) the probability that PrPsc is formed in relation to one neuron is independent of that of its neighbour.

Professionalism and quality in European business courses:utilising research to enhance student learning and promote employability - a pan-European study

This..paper provides a comparative analysis of Quality Management and standards in four European countries, (the UK, Austria, Slovenia and Romania) and in doing so addresses the gap in academic knowledge about how the introduction and implementation of Quality Management Strategies can both facilitate and enhance student learning within Universities.

Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate

Background: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. Methods: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). Results: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. Conclusions: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required. © 2014 Cancer Research UK. All rights reserved.

Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses

The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server. © 2013 Magdalena Molero-Abraham et al.

Influence of parameters of drying on laser induced diffuse reflectance of banana discs

Banana discs of 1 cm thickness were immersed into different antioxidant solutions to slow down potentially disturbing discoloration during drying. Samples were randomly split into 8 groups according to the 2^p experimental design. Two antioxidant solutions with 1.66% and 4.59% ascorbic acid, two levels of drying temperature with 50°C and 80°C, two levels of drying time with 6h and 8h were used or adjusted. Laser diodes of seven wavelengths (532, 635, 650, 780, 808, 850 and 1064 nm) were selected to illuminate the surface and light penetration pattern was evaluated on the basis of radial profiles. Profiles acquired at three wavelengths (532, 635 and 650 nm) were found to respond sensitively to adjusted parameters. As a result of drying, intensity decay was observed to move closer to incident point. Significant effect (p<0.01) of temperature, drying time and their interaction was found on extracted descriptive attributes of intensity profiles: full width at half maximum (FWHM), distance of inflection point (DIP) and slope of logarithmic decay (SLD). Beyond their presence, antioxidant concentration was neutral factor without significant contribution to the model. Results were in agreement with reference spectroscopic measurements, especially with NDVI index. Promising results suggest that evaluated method might be suitable for monitoring purposes during drying of fruits.

The migration crisis: representation of a border conflict in Hungarian, German and Pan-European television new coverage

In this article we review the methods used by television news channels in their reporting of the clashes between the Hungarian police and refugees at the Serbian-Hungarian border on 16th of September 2015. With the help of content analysis we examine the techniques used by each editorial board to portray events differently,resulting in dissimilar effects on recipients. During the analysis we examine news coverage for one specific day as presented by Hungarian, German and pan-European broadcasters. German news programs were chosen for comparison with Hungarian ones due to the fact that most of the refugees were heading towards Germany. We conclude that there are significant differences between the information that was broadcast according to television channels; owner expectations presumably play an important role in this.

In vivo characterization of myocardial tissue post myocardial infarction using combined fluorescence and diffuse reflectance spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region—one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees/severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

Remembering Pedro Pan: Faith, Family, and Freedom in Cuban-American Collective Memory , Lecture by Anita Casavantes Bradford

This flyer promotes the event "Remembering Pedro Pan: Faith, Family, and Freedom in Cuban-American Collective Memory Lecture by Anita Casavantes Bradford" and cosponsored by the Latin American and Caribbean Center and the Green Library

Legacy of Operation Pedro Pan, Lecture by Anita Casavantes Bradford

This flyer promotes the event "Legacy of Operation Pedro Pan", a lecture by author Anita Casavantes Bradford.

In Vivo Characterization of Myocardial Tissue Post Myocardial Infarction Using Combined Fluorescence and Diffuse Reflectance Spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on - (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region - one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees / severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.