Perforated tunnel exit regions and micro-pressure waves:geometrical influence

ACKNOWLEDGEMENTS The authors are grateful to the following bodies that provided financial support for the project: (i) China Scholarship Council, (ii) National Natural Science Foundation of China (Grant No. U1334201 and (iii) UK Engineering and Physical Sciences Research Council (Grant No. EP/G069441/1).Peer reviewedPublisher PD

Impaired access of lymphocytes to neoplastic prostate tissue is associated with neoangiogenesis in the tumour site

Recent reports demonstrated that neovasculature of certain murine tumours inhibits migration of lymphocytes to malignant tissues. We examined the possible existence of this phenomenon in human prostate adenocarcinoma by relating extent, patterns and composition of leucocyte infiltrates in adenocarinoma specimens (N=28) to microvessel density and percentages of these vessels expressing adhesion molecules CD54, CD106 and CD62E. Specimens of nodular hyperplasia (N=30) were used as a control for nonmalignant prostate. Increased microvessel density was detected in foci of adenocarcinoma, as compared with adjacent benign areas (P=0.004) or hyperplastic specimens (P=0.001). Only CD54 was detected on prostate vasculature; percentages of CD54-expressing vessels in adenocarcinoma lesions and adjacent areas were higher than in hyperplasia (P=0.041 and P=0.014, respectively). Infiltrating leucocytes were either scattered diffusely in tissue or organised into clusters mainly composed of CD4-positive lymphocytes; smaller percentage of tissue was occupied by clustered infiltrates in adenocarcinoma foci (mean=0.7; median=0; range=0–5) than in adjacent tissue (mean=2.5; median=1; range=0–15; P=.021) and hyperplasia (mean=1.9; median=2; range=0–5; P=.006). In adenocarcinoma foci, microvessel density tended to negatively correlate with percentage of tissue occupied by an overall leucocyte infiltrate (mean=8.6; median=7.5; range=30) and negatively correlated with percentage of tissue occupied by clustered infiltrate (P=0.045). Percentage of CD54-expressing vessels positively correlated with percentage of tissue occupied by an overall (mean=12; median=10; range=30; P=0.01) and clustered (P=0.023) infiltrate in hyperplasia, whereas in carcinoma-adjacent benign areas, correlation was detected only for clustered infiltrates (P=0.02). The results indicate that impaired access of lymphocytes to malignant lesions is associated with increased numbers of newly formed blood vessels, whereas vascular CD54 likely contributes to extravasation of lymphocytes only in benign prostate tissue

Cellular Prion Protein Expression Is Not Regulated by the Alzheimer's Amyloid Precursor Protein Intracellular Domain

There is increasing evidence of molecular and cellular links between Alzheimer's disease (AD) and prion diseases. The cellular prion protein, PrPC, modulates the post-translational processing of the AD amyloid precursor protein (APP), through its inhibition of the β-secretase BACE1, and oligomers of amyloid-β bind to PrPC which may mediate amyloid-β neurotoxicity. In addition, the APP intracellular domain (AICD), which acts as a transcriptional regulator, has been reported to control the expression of PrPC. Through the use of transgenic mice, cell culture models and manipulation of APP expression and processing, this study aimed to clarify the role of AICD in regulating PrPC. Over-expression of the three major isoforms of human APP (APP695, APP751 and APP770) in cultured neuronal and non-neuronal cells had no effect on the level of endogenous PrPC. Furthermore, analysis of brain tissue from transgenic mice over-expressing either wild type or familial AD associated mutant human APP revealed unaltered PrPC levels. Knockdown of endogenous APP expression in cells by siRNA or inhibition of γ-secretase activity also had no effect on PrPC levels. Overall, we did not detect any significant difference in the expression of PrPC in any of the cell or animal-based paradigms considered, indicating that the control of cellular PrPC levels by AICD is not as straightforward as previously suggested

Autonomous visual navigation of an indoor environment using a parsimonious, insect inspired familiarity algorithm

The navigation of bees and ants from hive to food and back has captivated people for more than a century. Recently, the Navigation by Scene Familiarity Hypothesis (NSFH) has been proposed as a parsimonious approach that is congruent with the limited neural elements of these insects’ brains. In the NSFH approach, an agent completes an initial training excursion, storing images along the way. To retrace the path, the agent scans the area and compares the current scenes to those previously experienced. By turning and moving to minimize the pixel-by-pixel differences between encountered and stored scenes, the agent is guided along the path without having memorized the sequence. An important premise of the NSFH is that the visual information of the environment is adequate to guide navigation without aliasing. Here we demonstrate that an image landscape of an indoor setting possesses ample navigational information. We produced a visual landscape of our laboratory and part of the adjoining corridor consisting of 2816 panoramic snapshots arranged in a grid at 12.7-cm centers. We show that pixel-by-pixel comparisons of these images yield robust translational and rotational visual information. We also produced a simple algorithm that tracks previously experienced routes within our lab based on an insect-inspired scene familiarity approach and demonstrate that adequate visual information exists for an agent to retrace complex training routes, including those where the path’s end is not visible from its origin. We used this landscape to systematically test the interplay of sensor morphology, angles of inspection, and similarity threshold with the recapitulation performance of the agent. Finally, we compared the relative information content and chance of aliasing within our visually rich laboratory landscape to scenes acquired from indoor corridors with more repetitive scenery.The authors received funding from a Research Council Faculty Investment Grant from the University of Oklahoma.Ye

Human native kappa opioid receptor functions not predicted by recombinant receptors: Implications for drug design

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