Moving in Semantic Space in Prodromal and Very Early Alzheimer's Disease : An Item-Level Characterization of the Semantic Fluency Task

The semantic fluency task is a widely used clinical tool in the diagnostic process of Alzheimer's disease. The task requires efficient mapping of the semantic space to produce as many items as possible within a semantic category. We examined whether healthy volunteers (n = 42) and patients with early Alzheimer's disease (24 diagnosed with amnestic Mild Cognitive Impairment and 18 with early Alzheimer's dementia) take advantage of and travel in the semantic space differently. With focus on the animal fluency task, we sought to emulate the detailed structure of the multidimensional semantic space by utilizing word2vec-method from the natural language processing domain. To render the resulting multidimensional semantic space visually comprehensible, we applied a dimensionality reduction algorithm (t-SNE), which enabled a straightforward division of the semantic space into sub-categories. Moving in semantic space was quantified with the number of items created, sub-categories visited, and switches and returns to these sub-categories. Multinomial logistic regression models were used to predict the diagnostic group with these independent variables. We found that returning to a sub-category provided additional information, besides the number of words produced in the task, to differentiate patients with Alzheimer's dementia from both amnestic Mild Cognitive Impairment patients and healthy controls. The results suggest that the frequency of returning to a sub-category may serve as an additional aid for clinicians in diagnosing early Alzheimer's disease. Moreover, our results imply that the combination of word2vec and subsequent t-SNE-visualization may offer a valuable tool for examining the semantic space and its sub-categories.Peer reviewe

Medial perirhinal cortex disambiguates confusable objects

Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer's disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region—the medial perirhinal cortex—is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damag

Electrical measurement of internal quantum efficiency and extraction efficiency of III-N light-emitting diodes

We propose a direct electrical measurement method for determining the extraction efficiency (EXE) and internal quantum efficiency(IQE) of III-Nitride light-emitting diodes(LEDs). The method is based on measuring the optical output power as a function of injection current at current densities near the external quantum efficiency (EQE) maximum and extracting IQE and EXE from the measurement data. In contrast to conventional methods, our method requires no low temperaturemeasurements or prior knowledge of the device structure. The method is far more convenient than commonly used methods because it enables measuring the EXE and IQE of different LED structures at room temperature directly in a repeatable and consistent way. This enables convenient comparison of LED structures. We apply the method to determine the IQE and EXE of one commercial LED and selected self-grown planar LED chips to compare the effects of different LED structure designs. Our results are in line with published experimental results and also give more insight to our earlier findings regarding the effects of growth parameters on the quantum efficiency. In addition, our measurement method allows estimating the Shockley-Read-Hall and radiative recombination parameters if the Auger parameter is known.Peer reviewe

Endorectal magnetic resonance imaging of prostatic cancer: comparison between fat-suppressed T2-weighted fast spin echo and three-dimensional dual-echo, steady-state sequences

Peer reviewe

Magnetic Resonance Imaging Findings in Finnish Spitz Dogs with Focal Epilepsy

Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were evaluated. General clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast enhancement after gadolinium injection was identified in this dog's right parietal cortex. However, no such changes were observed in repeated magnetic resonance images. Special emphasis was given to seizure history to determine any correlations between seizure intervals and MRI findings. Our results indicate that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity in detecting epileptogenic areas in our patients with focal seizures. Reversible MRI changes in 1 dog could have been caused by seizures

Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma

Summary Background Incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. Objectives To study the role of complement classical pathway components C1q, C1r and C1s in the progression of cSCC. Methods The mRNA levels of C1Q subunits, C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes (NHEKs), cSCC tumors in vivo and normal skin were analyzed with quantitative RT-PCR. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analyzed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. Results Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared to normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumors in vivo compared to normal skin. Abundant expression of C1r and C1s by tumor cells was detected in invasive sporadic cSCCs and recessive dystrophic epidermolysis bullosa-associated cSCCs, whereas the expression of C1r and C1s was lower in cSCC in situ, actinic keratosis, and normal skin. Knockdown of C1r and C1s expression in cSCC cells inhibited activation of ERK1/2 and Akt, promoted apoptosis of cSCC cells and significantly suppressed growth and vascularization of human cSCC xenograft tumors in vivo. Conclusions These results provide evidence for the role of tumor cell-derived C1r and C1s in the progression of cSCC and identify them as biomarkers and putative therapeutic targets in cSCC. This article is protected by copyright. All rights reserved.Peer reviewe

Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, and the prognosis of patients with metastatic disease is poor. There is an emerging need to identify molecular markers for predicting aggressive behaviour of cSCC. Here, we have examined the role of tight junction (TJ) components in the progression of cSCC. The expression pattern of mRNAs for TJ components was determined with RNA sequencing and oligonucleotide array-based expression analysis from cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK, n=5). The expression of CLDN11 was specifically elevated in primary cSCC cell lines (n=5), but low or absent in metastatic cSCC cell lines (n=3) and NHEKs. Claudin-11 was detected in cell-cell contacts of primary cSCC cells in culture by indirect immunofluorescence analysis. Analysis of a large panel of tissue samples from sporadic UV-induced cSCC (n=65), cSCC in situ (n=56), actinic keratoses (n=31), seborrhoeic keratoses (n=7) and normal skin (n=16) by immunohistochemistry showed specific staining for claudin-11 in intercellular junctions of keratinizing tumor cells in well and moderately differentiated cSCCs, whereas no staining for claudin-11 was detected in poorly differentiated tumors. The expression of claudin-11 in cSCC cells was dependent on the activity of p38 delta MAPK and knock-down of claudin-11 enhanced cSCC cell invasion. These findings provide evidence for the role of claudin-11 in regulation of cSCC invasion and suggest loss of claudin-11 expression in tumor cells as a biomarker for advanced stage of cSCC

Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma

Background The incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. Objectives To study the role of the complement classical pathway components C1q, C1r and C1s in the progression of cSCC. Methods The mRNA levels of C1Q subunits and C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes, cSCC tumours in vivo and normal skin were analysed with quantitative real-time polymerase chain reaction. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analysed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. Results Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared with normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumours in vivo compared with normal skin. Abundant expression of C1r and C1s by tumour cells was detected in invasive sporadic cSCCs and recessive dystrophic epidermolysis bullosa-associated cSCCs, whereas the expression of C1r and C1s was lower in cSCC in situ, actinic keratosis and normal skin. Knockdown of C1r and C1s expression in cSCC cells inhibited activation of extracellular signal-related kinase 1/2 and Akt, promoted apoptosis of cSCC cells and significantly suppressed growth and vascularization of human cSCC xenograft tumours in vivo. Conclusions These results provide evidence for the role of tumour-cell-derived C1r and C1s in the progression of cSCC and identify them as biomarkers and putative therapeutic targets in cSCC.</p