Photoluminescence revealed higher order plasmonic resonance modes and their unexpected frequency blue shifts in silver-coated silica nanoparticle antennas

© 2019 by the authors. Higher order plasmonic resonance modes and their frequency blue shifts in silver-coated silica nanoparticle antennas are studied. Synthesizing them with a wet chemistry method, silica (SiO2) nanoparticles were enclosed within silver shells with different thicknesses. A size-dependent Drude model was used to model the plasmonic shells and their optical losses. Two higher order plasmonic resonances were identified for each case in these simulations. The photoluminescence spectroscopy (PL) experimental results, in good agreement with their simulated values, confirmed the presence of those two higher order resonant modes and their resonance frequencies. When compared with pure metallic Ag nanoparticles, size-induced blue shifts were observed in these resonance frequencies

Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses

$\textit{Introduction}$ Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such neuroinflammation relates to other aspects of neuropathology (e.g., tau and amyloid pathology) as well as to structural and functional changes in the brain and symptoms (as assessed via MRI and clinical and neuropsychological assessment). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows $\textit{in vivo}$ imaging of inflammation, amyloid and tau deposition, together with neuropsychological profiling, magnetic resonance imaging (MRI) and peripheral biomarker analysis. \textit{Methods & analysis} Using PET imaging of the ligand [11C]PK11195 we will test for increased neuroinflammation $\textit{in vivo}$ in patients with Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and tau deposition (assessed using $^{11}$C-labelled Pittsburgh Compound B ([$^{11}$C]PiB) and $^{18}$F-labelled AV-1451 respectively), as well as structural and functional connectivity changes found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central (i.e., neural) and peripheral inflammation. Finally, we will examine whether neuroinflammatory changes seen on PET imaging are associated with global and domain specific cognitive impairments, or predict cognitive decline over 12 months. \textit{Ethics & dissemination} The study protocol was approved by the local ethics committee, East of England - Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also ARSAC approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of neuroscience as well as clinical neurology and psychiatry. $\textit{Strengths}$ Multimodal deep phenotyping Comparisons between diseases as well as with controls Longitudinal neuropsychology data Comparison of central and peripheral inflammation $\textit{Weaknesses}$ Lack of longitudinal neuroimaging Not a prospective study, unable to assess causationThe study is funded by the UK National Institute of Health Research Cambridge Biomedical Research Unit in Dementia (Project 4 - RNAG/293). JBR is supported by the Wellcome Trust (103838). JPC is supported by the UK National Institute of Health Research Biomedical Research Centre at Cambridge. PVR is supported by the PSP Association

Inherited pathogenic mitochondrial DNA mutations and gastrointestinal stem cell populations.

Inherited mitochondrial DNA (mtDNA) mutations cause mitochondrial disease, but mtDNA mutations also occur somatically and accumulate during ageing. Studies have shown that the mutation load of some inherited mtDNA mutations decreases over time in blood, suggesting selection against the mutation. However, it is unknown whether such selection occurs in other mitotic tissues, and where it occurs within the tissue. Gastrointestinal epithelium is a canonical mitotic tissue rapidly renewed by stem cells. Intestinal crypts (epithelium) undergo monoclonal conversion with a single stem cell taking over the niche and producing progeny. We show: (1) that there is a significantly lower mtDNA mutation load in the mitotic epithelium of the gastrointestinal tract when compared to the smooth muscle in the same tissue in patients with the pathogenic m.3243A>G and m.8344A>G mutations; (2) that there is considerable variation seen in individual crypts, suggesting changes in the stem cell population; (3) that this lower mutation load is reflected in the absence of a defect in oxidative phosphorylation in the epithelium. This suggests that there is selection against inherited mtDNA mutations in the gastrointestinal stem cells that is in marked contrast to the somatic mtDNA mutations that accumulate with age in epithelial stem cells leading to a biochemical defect. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.Wellcome Trust. Grant Number: G096919 MRC ESRC EPSRC BBSRC Newcastle University Centre for Ageing and Vitalit

A new classification of the long-horned caddisflies (Trichoptera: Leptoceridae) based on molecular data

Background: Leptoceridae are among the three largest families of Trichoptera (caddisflies). The current classification is founded on a phylogenetic work from the 1980's, based on morphological characters from adult males, i.e. wing venation, tibial spur formula and genital morphology. In order to get a new opinion about the relationships within the family, we undertook a molecular study of the family based on sequences from five genes, mitochondrial COI and the four nuclear genes CAD, EF-1 alpha, IDH and POL. Results: The resulting phylogenetic hypotheses are more or less congruent with the morphologically based classification, with most genera and tribes recovered as monophyletic, but with some major differences. For monophyly of the two subfamilies Triplectidinae and Leptocerinae, one tribe of each was removed and elevated to subfamily status; however monophyly of some genera and tribes is in question. All clades except Leptocerinae, were stable across different analysis methods. Conclusions: We elevate the tribes Grumichellini and Leptorussini to subfamily status, Grumichellinae and Leptorussinae, respectively. We also propose the synonymies of Ptochoecetis with Oecetis and Condocerus with Hudsonema.authorCount :

Investigation of initiation of gigantic jets connecting thunderclouds to the ionosphere

The initiation of giant electrical discharges called as "gigantic jets" connecting thunderclouds to the ionosphere is investigated by numerical simulation method in this paper. Using similarity relations, the triggering conditions of streamer formation in laboratory situations are extended to form a criterion of initiation of gigantic jets. The energy source causing a gigantic jet is considered due to the quasi-electrostatic field generated by thunderclouds. The electron dynamics from ionization threshold to streamer initiation are simulated by the Monte Carlo technique. It is found that gigantic jets are initiated at a height of ~18-24 km. This is in agreement with the observations. The method presented in this paper could be also applied to the analysis of the initiation of other discharges such as blue jets and red sprites.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Linear, Deterministic, and Order-Invariant Initialization Methods for the K-Means Clustering Algorithm

Over the past five decades, k-means has become the clustering algorithm of choice in many application domains primarily due to its simplicity, time/space efficiency, and invariance to the ordering of the data points. Unfortunately, the algorithm's sensitivity to the initial selection of the cluster centers remains to be its most serious drawback. Numerous initialization methods have been proposed to address this drawback. Many of these methods, however, have time complexity superlinear in the number of data points, which makes them impractical for large data sets. On the other hand, linear methods are often random and/or sensitive to the ordering of the data points. These methods are generally unreliable in that the quality of their results is unpredictable. Therefore, it is common practice to perform multiple runs of such methods and take the output of the run that produces the best results. Such a practice, however, greatly increases the computational requirements of the otherwise highly efficient k-means algorithm. In this chapter, we investigate the empirical performance of six linear, deterministic (non-random), and order-invariant k-means initialization methods on a large and diverse collection of data sets from the UCI Machine Learning Repository. The results demonstrate that two relatively unknown hierarchical initialization methods due to Su and Dy outperform the remaining four methods with respect to two objective effectiveness criteria. In addition, a recent method due to Erisoglu et al. performs surprisingly poorly.Comment: 21 pages, 2 figures, 5 tables, Partitional Clustering Algorithms (Springer, 2014). arXiv admin note: substantial text overlap with arXiv:1304.7465, arXiv:1209.196

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2

Background and Objectives: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study