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\"A comprehensive and thought-provoking investigation into one of the most polarizing words in the English language\"-- Provided by publisher.

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) slows the progression of caries and remineralizes enamel subsurface lesions. The aim of this study was to determine the ability of CPP-ACP to increase the incorporation of fluoride into plaque and to promote enamel remineralization in situ. Randomized, double-blind, cross-over studies involved mouthrinses and dentifrices containing CPP-ACP and fluoride. The mouthrinses were used for 60 sec, three times/day for 5 days, and supragingival plaque was collected and analyzed for F. The dentifrices were rinsed as a water slurry for 60 sec four times/day for 14 days in an in situ model. The addition of 2% CPP-ACP to the 450-ppm-F mouthrinse significantly increased the incorporation of fluoride into plaque. The dentifrice containing 2% CPP-ACP produced a level of remineralization similar to that achieved with a dentifrice containing 2800 ppm F. The dentifrice containing 2% CPP-ACP plus 1100 ppm F was superior to all other formulations.

\"A sequel to Sir Arthur C. Clarke's Nebula Award-winning novella \"A Meeting with Medusa,\" this novel continues the thrilling adventure of astronaut Howard Falcon, humanity first explorer of Jupiter from two modern science fiction masters. Howard Falcon almost lost his life in an accident as the first human astronaut to explore the atmosphere of Jupiter and a combination of human ingenuity and technical expertise brought him back. But he is no longer himself. Instead, he has been changed into an augmented human: part man, part machine, and exceptionally capable. With permission from the Clarke Estate, Stephen Baxter and Alastair Reynolds continue this beloved writer enduring vision and have created a fresh story for new readers. The Medusa Chronicles charts Falcon journey through the centuries granted by his new body, but always back to mysteries of Jupiter and the changing interaction between humanity and the universe. A compelling read full of incredible action right from the beginning, this is a modern classic in the spirit of 2001 and The Martian.\"--Amazon.

Observations of an ultrafast accretion-disk wind in the X-ray spectrum of a nearby ultraluminous infrared galaxy support the theory that such winds affect the evolution of supermassive black holes and their host galaxies. Growing in the wind Francesco Tombesi et al . report the detection of a powerful accretion-disk wind with a mildly relativistic velocity in the X-ray spectrum of IRAS F11119+3257, a nearby ( z = 0.189) optically classified type 1 ultraluminous infrared galaxy hosting a powerful molecular outflow. The energetics of these winds are consistent with the suggestion that active galactic nuclei winds can provide an efficient way to transfer energy to the interstellar medium and support the theory that such winds affect the evolution of supermassive black holes and their host galaxies. Powerful winds driven by active galactic nuclei are often thought to affect the evolution of both supermassive black holes and their host galaxies, quenching star formation and explaining the close relationship between black holes and galaxies 1 , 2 . Recent observations of large-scale molecular outflows 3 , 4 , 5 , 6 , 7 , 8 in ultraluminous infrared galaxies support this quasar-feedback idea, because they directly trace the gas from which stars form. Theoretical models 9 , 10 , 11 , 12 suggest that these outflows originate as energy-conserving flows driven by fast accretion-disk winds. Proposed connections between large-scale molecular outflows and accretion-disk activity in ultraluminous galaxies were incomplete 3 , 4 , 5 , 6 , 7 , 8 because no accretion-disk wind had been detected. Conversely, studies of powerful accretion-disk winds have until now focused only on X-ray observations of local Seyfert galaxies 13 , 14 and a few higher-redshift quasars 15 , 16 , 17 , 18 , 19 . Here we report observations of a powerful accretion-disk wind with a mildly relativistic velocity (a quarter that of light) in the X-ray spectrum of IRAS F11119+3257, a nearby (redshift 0.189) optically classified type 1 ultraluminous infrared galaxy hosting a powerful molecular outflow 6 . The active galactic nucleus is responsible for about 80 per cent of the emission, with a quasar-like luminosity 6 of 1.5 × 10 46 ergs per second. The energetics of these two types of wide-angle outflows is consistent with the energy-conserving mechanism 9 , 10 , 11 , 12 that is the basis of the quasar feedback 1 in active galactic nuclei that lack powerful radio jets (such jets are an alternative way to drive molecular outflows).

The results from cross sectional and longitudinal studies show that periodontitis is closely associated with cognitive impairment (CI) and Alzhemer's Disease (AD). Further, studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain. However, neuropathology resulting from Pg oral application is not known. In this work, we tested the hypothesis that repeated exposure of wild type C57BL/6 mice to orally administered Pg results in neuroinflammation, neurodegeneration, microgliosis, astrogliosis and formation of intra- and extracellular amyloid plaque and neurofibrillary tangles (NFTs) which are pathognomonic signs of AD. Experimental chronic periodontitis was induced in ten wild type 8-week old C57BL/6 WT mice by repeated oral application (MWF/week) of Pg/gingipain for 22 weeks (experimental group). Another 10 wild type 8-week old C57BL/6 mice received vehicle alone (control group) MWF per week for 22 weeks. Brain tissues were collected and the presence of Pg/gingipain was determined by immunofluorescence (IF) microscopy, confocal microscopy, and quantitative PCR (qPCR). The hippocampi were examined for the signs of neuropathology related to AD: TNFα, IL1β, and IL6 expression (neuroinflammation), NeuN and Fluoro Jade C staining (neurodegeneration) and amyloid beta1-42 (Aβ42) production and phosphorylation of tau protein at Ser396 were assessed by IF and confocal microscopy. Further, gene expression of amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), a disintegrin and metalloproteinase domain-containing protein10 (ADAM10) for α-secretase and presenilin1 (PSEN1) for ɣ-secretase, and NeuN (rbFox3) were determined by RT-qPCR. Microgliosis and astrogliosis were also determined by IF microscopy. Pg/gingipain was detected in the hippocampi of mice in the experimental group by immunohistochemistry, confocal microscopy, and qPCR confirming the translocation of orally applied Pg to the brain. Pg/gingipain was localized intra-nuclearly and peri-nuclearly in microglia (Iba1+), astrocytes (GFAP+), neurons (NeuN+) and was evident extracellularly. Significantly greater levels of expression of IL6, TNFα and IL1β were evident in experimental as compared to control group (p<0.01, p<0.00001, p<0.00001 respectively). In addition, microgliosis and astrogliosis were evident in the experimental but not in control group (p <0.01, p<0.0001 respectively). Neurodegeneration was evident in the experimental group based on a fewer number of intact neuronal cells assessed by NeuN positivity and rbFOX3 gene expression, and there was a greater number of degenerating neurons in the hippocampi of experimental mice assessed by Fluoro Jade C positivity. APP and BACE1 gene expression were increased in experimental group compared with control group (p<0.05, p<0.001 respectively). PSEN1 gene expression was higher in experimental than control group but the difference was not statistically significant (p = 0.07). ADAM10 gene expression was significantly decreased in experimental group compared with control group (p<0.01). Extracellular Aβ42 was detected in the parenchyma in the experimental but not in the control group (p< 0.00001). Finally, phospho-Tau (Ser396) protein was detected and NFTs were evident in experimental but not in the control group (p<0.00001). This study is the first to show neurodegeneration and the formation of extracellular Aβ42 in young adult WT mice after repeated oral application of Pg. The neuropathological features observed in this study strongly suggest that low grade chronic periodontal pathogen infection can result in the development of neuropathology that is consistent with that of AD.

The nexus between periodontal inflammation and the polymicrobial biofilm in the gingival sulcus is critical to understanding the pathobiology of periodontitis. Both play a major role in the etiology and pathogenesis of periodontal diseases and each reinforces the other. However, this nexus is also at the center of a significant conundrum for periodontology. For all mucosal polymicrobial biofilms, the most confounding issue is the paradoxical relationship between inflammation, infection, and disease. Despite significant advances made in both periodontal microbiology and periodontal pathobiology, the issue of which comes first, the inflammatory response or the change to a dysbiotic subgingival microbiota, is still debated. In this paper, we present a model for the pathogenesis of periodontitis based on the central role of inflammation and how this modulates the polymicrobial biofilm within the context of the continuum of health, gingivitis, and periodontitis. We propose a new model termed \"Inflammation-Mediated Polymicrobial-Emergence and Dysbiotic-Exacerbation\" (IMPEDE), which is designed to integrate into and complement the 2017 World Workshop Classification of Periodontitis.

This study assessed the efficacy of 60% CPP-ACP to remineralise white spot lesions (WSLs) in enamel and to occlude patent dentinal tubules in a double-blind, randomized, cross-over, in situ study. Human enamel specimens with subsurface lesions (WSLs) and root dentine specimens with open dentinal tubules were prepared and inserted into intra-oral appliances worn by volunteers. Participants wore the appliances 24 h a day for four 14-consecutive day treatment periods with a 7-day washout period between treatments. Four treatments applied with a micro-brush once daily were 60% CPP-ACP with and without 1100ppm F as SnF 2 , 1100ppm F as SnF 2 alone and a placebo as negative control. Mineral content was measured using transverse microradiography and dentine tubules were examined using scanning electron microscopy (SEM). The data were analysed using a repeated measures ANOVA with a Sidak adjustment for multiple comparisons. Once daily application of 60% CPP-ACP with or without SnF 2 produced 36.6 ± 1.6% and 28.8 ± 1.5% remineralisation of the WSLs respectively, and both were significantly higher ( p  < 0.0001) than that for treatment by SnF 2 alone (8.8 ± 0.7%) or placebo control (2.3 ± 0.4%). SEM analysis of the dentine samples showed that daily application of 60% CPP-ACP with or without SnF 2 produced near complete dentinal tubule occlusion.

Neuroblastoma (NB) is the most common extracranial solid malignancy in children. Despite current aggressive treatment regimens, the prognosis for high‐risk NB patients remains poor, with the survival of less than 40%. Amplification/stabilization of MYCN oncogene, in NB is associated with a high risk of recurrence. Thus, there is an urgent need for novel therapeutics. The deregulated expression of microRNA (miR) is reported in NB; nonetheless, its effect on MYCN regulation is poorly understood. First, we identified that miR‐15a‐5p, miR‐15b‐5p, and miR‐16‐5p (hereafter miR‐15a, miR‐15b or miR‐16) were down‐regulated in patient‐derived xenografts (PDX) with high MYCN expression. MiR targeting sequences on MYCN mRNA were predicted using online databases such as TargetScan and miR database. The R2 database, containing 105 NB patients, showed an inverse correlation between MYCN mRNA and deleted in lymphocytic leukemia (DLEU) 2, a host gene of miR‐15. Moreover, overexpression of miR‐15a, miR‐15b or miR‐16 significantly reduced the levels of MYCN mRNA and N‐Myc protein. Conversely, inhibiting miR dramatically enhanced MYCN mRNA and N‐Myc protein levels, as well as increasing mRNA half‐life in NB cells. By performing immunoprecipitation assays of argonaute‐2 (Ago2), a core component of the RNA‐induced silencing complex, we showed that miR‐15a, miR‐15b and miR‐16 interact with MYCN mRNA. Luciferase reporter assays showed that miR‐15a, miR‐15b and miR‐16 bind with 3’UTR of MYCN mRNA, resulting in MYCN suppression. Moreover, induced expression of miR‐15a, miR‐15b and miR‐16 significantly reduced the proliferation, migration, and invasion of NB cells. Finally, transplanting miR‐15a‐, miR‐15b‐ and miR‐16‐expressing NB cells into NSG mice repressed tumor formation and MYCN expression. These data suggest that miR‐15a, miR‐15b and miR‐16 exert a tumor‐suppressive function in NB by targeting MYCN. Therefore, these miRs could be considered as potential targets for NB treatment. A model summarizing how miR‐15a, miR‐15b, and miR‐16 suppress tumor progression in neuroblastoma by targeting MYCN. When miRs are overexpressed, argonaute‐2‐mediated interaction of miR with MYCN mRNA increases, followed by degradation of MYCN, leading to neuroblastoma regression.

L-line route to black holes The emission line arising from a transition of an electron from the iron K shell to the ground state (the K line) is prominent in the reflection spectrum of the hard X-ray continuum irradiating dense accreting matter around a black hole. The corresponding iron L-line emission should be detectable when iron abundance is high. That's the theory, and now broad iron L-line emission has been observed, together with the broad K line in the narrow-line Seyfert galaxy 1H0707. There is a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the hole, a timescale comparable to the light-crossing time of the innermost radii around a supermassive black hole. This discovery opens a window on events close to the black hole event horizon in these objects. Emission arising from a transition of an electron from the iron K shell to the ground state (the K line) is prominent in the reflection spectrum created by the hard X-ray continuum irradiating the dense accreting matter around a black hole. Here the presence of both iron K and L emission is reported in the spectrum of the active galaxy 1H 0707-495. There is a 'reverberation lag' with a timescale comparable to the light-crossing time of the innermost radii around a supermassive black hole. Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG–6-30-15 (ref. 1 ), broad iron K lines have been found in emission from several other Seyfert galaxies 2 , from accreting stellar-mass black holes 3 and even from accreting neutron stars 4 . The iron K line is prominent in the reflection spectrum 5 , 6 created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion 7 of the line makes it sensitive to the strong gravity and spin of the black hole 8 . The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy 9 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.