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A new Earth system model of intermediate complexity – CANOPS-GRB v1.0 – is presented for use in quantitatively assessing the dynamics and stability of atmospheric and oceanic chemistry on Earth and Earth-like planets over geologic timescales. The new release is designed to represent the coupled major element cycles of C, N, P, O, and S, as well as the global redox budget (GRB) in Earth's exogenic (ocean–atmosphere–crust) system, using a process-based approach. This framework provides a mechanistic model of the evolution of atmospheric and oceanic O2 levels on geologic timescales and enables comparison with a wide variety of geological records to further constrain the processes driving Earth's oxygenation. A complete detailed description of the resulting Earth system model and its new features are provided. The performance of CANOPS-GRB is then evaluated by comparing a steady-state simulation under present-day conditions with a comprehensive set of oceanic data and existing global estimates of bio-element cycling. The dynamic response of the model is also examined by varying phosphorus availability in the exogenic system. CANOPS-GRB reliably simulates the short- and long-term evolution of the coupled C–N–P–O2–S biogeochemical cycles and is generally applicable across most period of Earth's history given suitable modifications to boundary conditions and forcing regime. The simple and adaptable design of the model also makes it useful to interrogate a wide range of problems related to Earth's oxygenation history and Earth-like exoplanets more broadly. The model source code is available on GitHub and represents a unique community tool for investigating the dynamics and stability of atmospheric and oceanic chemistry on long timescales.

The evolution of land plants in terrestrial environments brought about one of the most dramatic shifts in the history of the Earth system — the birth of modern soils — and likely stimulated massive changes in marine biogeochemistry and climate. In particular, multiple marine mass extinctions characterized by widespread anoxia, including the Late Devonian mass extinction around 375 million years ago (Ma), may have been linked to terrestrial nutrient release driven by newly-rooted landscapes. Here, we use recently generated constraints from Earth’s lacustrine rock record as variable inputs in an Earth system model of the coupled C-N-P-O2-S biogeochemical cycles in order to evaluate whether recorded changes to phosphorus fluxes would be adequate to sustain Devonian marine biogeochemical perturbations and extinction dynamics. Results show that globally scaled riverine phosphorus export during the Late Devonian mass extinction generates widespread marine anoxia and produces carbon isotope, temperature, oxygen, and carbon dioxide perturbations generally consistent with the geologic record. Similar results for a competing extinction mechanism, large scale volcanism, suggest the Late Devonian mass extinction was likely multifaceted with both land plants and volcanism as contributing factors.

The global-scale oxygenation of Earth’s surface represents one of the most fundamental chemical transformations in our planet’s history. There is empirical and theoretical evidence for at least two...

Periodontal diseases are common inflammatory diseases that are induced by infection with periodontal bacteria such as Porphyromonas gingivalis (Pg). The association between periodontal diseases and many types of systemic diseases has been demonstrated; the term "periodontal medicine" is used to describe how periodontal infection/inflammation may impact extraoral health. However, the molecular mechanisms by which the factors produced in the oral cavity reach multiple distant organs and impact general health have not been elucidated. Extracellular vesicles (EVs) are nano-sized spherical structures secreted by various types of cells into the tissue microenvironment, and influence pathophysiological conditions by delivering their cargo. However, a detailed understanding of the effect of EVs on periodontal medicine is lacking. In this study, we investigated whether EVs derived from Pg-infected macrophages reach distant organs in mice and influence the pathophysiological status. EVs were isolated from human macrophages, THP-1 cells, infected with Pg. We observed that EVs from Pg-infected THP-1 cells (Pg-inf EVs) contained abundant core histone proteins such as histone H3 and translocated to the lungs, liver, and kidneys of mice. Pg-inf EVs also induced pulmonary injury, including edema, vascular congestion, inflammation, and collagen deposition causing alveoli destruction. The Pg-inf EVs or the recombinant histone H3 activated the NF-κB pathway, leading to increase in the levels of pro-inflammatory cytokines in human lung epithelial A549 cells. Our results suggest a possible mechanism by which EVs produced in periodontal diseases contribute to the progression of periodontal medicine.

The immune response in periodontal lesions is involved in the progression of periodontal disease. Therefore, it is important to find a bioactive substance that has anti-inflammatory effects in periodontal lesions. This study aimed to examine if nobiletin, which is found in the peel of citrus fruits, could inhibit inflammatory responses in interleukin (IL)-1β-stimulated human periodontal ligament cells (HPDLCs). The release of cytokines (IL-6, IL-8, CXCL10, CCL20, and CCL2) and matrix metalloproteinases (MMP-1 and MMP-3) was assessed by ELISA. The expression of cell adhesion molecules (ICAM-1and VCAM-1) and the activation of signal transduction pathways (nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt)) in HPDLCs were detected by Western blot analysis.&nbsp, Our experiments revealed that nobiletin decreased the expression of inflammatory cytokines, cell adhesion molecules, and MMPs in IL-1β-stimulated HPDLCs. Moreover, we revealed that nobiletin treatment could suppress the activation of the NF-κB, MAPKs, and Akt pathways. These findings indicate that nobiletin could inhibit inflammatory reactions in IL-1β-stimulated HPDLCs by inhibiting multiple signal transduction pathways, including NF-κB, MAPKs, and Akt.

Earth's modern atmosphere is highly oxygenated and is a remotely detectable signal of its surface biosphere. However, the lifespan of oxygen-based biosignatures in Earth's atmosphere remains uncertain, particularly for the distant future. Here we use a combined biogeochemistry and climate model to examine the likely timescale of oxygen-rich atmospheric conditions on Earth. Using a stochastic approach, we find that the mean future lifespan of Earth's atmosphere with oxygen levels more than 1% of the present atmospheric level is 1.08+-0.14 billion years. The model projects that a deoxygenation of the atmosphere, with atmospheric oxygen dropping sharply to levels reminiscnet of the Archaean Earth, will most probably be triggered before the inception of moist greenhouse conditions in Earth's climate system and before the extensive loss of surface water from the atmosphere. We find that future deoxygenation is an inevitable consequence of increasing solar fluxes, whereas its precise timing is modulated by the exchange flux of reducing power between the mantle and the ocean-atmosphere-crust system. Our results suggest that the planetary carbonate-silicate cycle will tend to lead to terminally CO2-limited biospheres and rapid atmospheric deoxygenation, emphasizing the need for robust atmospheric biosignatures applicable to weakly oxygenated and anoxic exoplanet atmospheres and highlighting the potential importance of atmospheric organic haze during the terminal stages of planetary habitability., Manuscript currently in press in Nature Geoscience

Sudachitin, which is a polymethoxylated flavonoid found in the peel of Citrus sudachi, has some biological activities. However, the effect of sudachitin on periodontal resident cells is still uncertain. The aim of this study was to examine if sudachitin could decrease the expression of inflammatory mediators such as cytokines, chemokines, or matrix metalloproteinase (MMP) in interleukin- (IL-) 1β-stimulated human periodontal ligament cells (HPDLC). Sudachitin inhibited IL-1β-induced IL-6, IL-8, CXC chemokine ligand (CXCL)10, CC chemokine ligand (CCL)2, MMP-1, and MMP-3 production in HPDLC. On the other hand, tissue inhibitor of metalloproteinase- (TIMP-) 1 expression was increased by sudachitin treatment. Moreover, we found that the nuclear factor- (NF-) κB and protein kinase B (Akt) pathways in the IL-1β-stimulated HPDLC were inhibited by sudachitin treatment. These findings indicate that sudachitin is able to reduce inflammatory mediator production in IL-1β-stimulated HPDLC by inhibiting NF-κB and Akt pathways.

Sudachitin, which is a polymethoxylated flavonoid found in the peel of Citrus sudachi, has some biological activities. However, the effect of sudachitin on periodontal resident cells is still uncertain. The aim of this study was to examine if sudachitin could decrease the expression of inflammatory mediators such as cytokines, chemokines, or matrix metalloproteinase (MMP) in interleukin- (IL-) 1β-stimulated human periodontal ligament cells (HPDLC). Sudachitin inhibited IL-1β-induced IL-6, IL-8, CXC chemokine ligand (CXCL)10, CC chemokine ligand (CCL)2, MMP-1, and MMP-3 production in HPDLC. On the other hand, tissue inhibitor of metalloproteinase- (TIMP-) 1 expression was increased by sudachitin treatment. Moreover, we found that the nuclear factor- (NF-) κB and protein kinase B (Akt) pathways in the IL-1β-stimulated HPDLC were inhibited by sudachitin treatment. These findings indicate that sudachitin is able to reduce inflammatory mediator production in IL-1β-stimulated HPDLC by inhibiting NF-κB and Akt pathways.

Earth’s orbital variations on timescales of 104–105 years, known as Milankovitch cycles, have played a critical role in pacing climate change and ecosystem dynamics, through glacial and/or monsoon dynamics. However, the climatic and biotic consequences of these cycles on much longer (~ 107 years) timescales remain unclear, due to a lack of long proxy records with precise age constraints. Here, we show ~ 10-Myr scale variations in early Mesozoic (250–180 Ma) records of lake-level, desert distribution, biogenic-silica burial flux, atmospheric CO2 levels (pCO2), and sea-surface-temperature (SST). Their phase relationships, coupled with carbon cycle modeling results, suggest that orbitally-paced summer monsoon dynamics modulates changes in terrestrial weatherability by ~ 20%, affecting changes in pCO2 of up to 500–1,000 ppmv and 3–7 °C SST. We also infer that these ~ 10-Myr scale climatic variations could have been causally linked to biotic turnover, size variations in dinosaur footprints, and tetrapod dispersal, potentially through spatio-temporal variations in resource availability and arid-hot climatic barriers at low-middle latitudes.

Objectives: The effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of microorganisms such as non-Candida albicans Candida (NCAC) and methicillin-resistant Staphylococcus aureus (MRSA), frequently detected in oral infections in immunocompromised and/or elderly people, to denture resin material, are still unclear. Here, we report the effects of MPC-polymer on the adherence of C. albicans, NCAC, and MRSA to acrylic denture resin. Methods: Sixteen strains of C. albicans, seven strains of C. glabrata, two strains of C. tropicalis, one strain of C. parapsilosis, and six strains of MRSA were used. We cultured the fungal/bacterial strains and examined the cell growth and adherence of fungi/bacteria to mucin-coated acrylic denture resin plates (ADRP) with or without MPC-polymer coating, by scanning electron microscopy. The cell surface hydrophobicity of the fungal/bacterial strains was measured by the adsorption to hydrocarbons. Results: MPC-polymer did not affect the growth of all strains of Candida species and MRSA, but significantly suppressed adherence to ADRP in most strains of C. albicans and all strains of NCAC and MRSA. A significant positive correlation was found between cell hydrophobicity and the reduction rates of microbial adherence to ADRP treated with 5% of MPC-polymer. Conclusions: MPC-polymer treatment for acrylic resin material suppresses the adherence of C. albicans, NCAC and MRSA via their hydrophilicity interaction. Clinical significance: The application of MPC-polymer for denture hygiene is potent to prevent oral candidiasis, denture stomatitis and opportunistic infection, caused by Candida species and MRSA, via suppressing the adherence of those fungus/bacteria.

Earth's ocean-atmosphere system has undergone a dramatic but protracted increase in oxygen (O2) abundance. This environmental transition ultimately paved the way for the rise of multicellular life and provides a blueprint for how a biosphere can transform a planetary surface. However, estimates of atmospheric oxygen levels for large intervals of Earth's history still vary by orders of magnitude-foremost for Earth's middle history. Historically, estimates of mid-Proterozoic (1.9-0.8 Ga) atmospheric oxygen levels are inferred based on the kinetics of reactions occurring in soils or in the oceans, rather than being directly tracked by atmospheric signatures. Rare oxygen isotope systematics-based on quantifying the rare oxygen isotope 17O in addition to the conventionally determined 16O and 18O-provide a means to track atmospheric isotopic signatures and thus potentially provide more direct estimates of atmospheric oxygen levels through time. Oxygen isotope signatures that deviate strongly from the expected mass-dependent relationship between 16O, 17O, and 18O develop during ozone formation, and these "mass-independent" signals can be transferred to the rock record during oxidation reactions in surface environments that involve atmospheric O2. The magnitude of these signals is dependent upon pO2, pCO2, and the overall extent of biospheric productivity. Here, we use a stochastic approach to invert the mid-Proterozoic Δ17O record for a new estimate of atmospheric pO2, leveraging explicit coupling of pO2 and biospheric productivity in a biogeochemical Earth system model to refine the range of atmospheric pO2 values that is consistent with a given observed Δ17O. Using this approach, we find new evidence that atmospheric oxygen levels were less than ∼1% of the present atmospheric level (PAL) for at least some intervals of the Proterozoic Eon.

The evolution of different forms of photosynthetic life has profoundly altered the activity level of the biosphere, radically reshaping the composition of Earth's oceans and atmosphere over time. However, the mechanistic impacts of a primitive photosynthetic biosphere on Earth's early atmospheric chemistry and climate are poorly understood. Here, we use a global redox balance model to explore the biogeochemical and climatological effects of different forms of primitive photosynthesis. We find that a hybrid ecosystem of H2-based and Fe-based anoxygenic photoautotrophs - organisms that perform photosynthesis without producing oxygen - gives rise to a strong nonlinear amplification of Earth's methane (CH4) cycle, and would thus have represented a critical component of Earth's early climate system before the advent of oxygenic photosynthesis. Using a Monte Carlo approach, we find that a hybrid photosynthetic biosphere widens the range of geochemical conditions that allow for warm climate states well beyond either of these metabolic processes acting in isolation. Our results imply that Earth's early climate was governed by a novel and poorly explored set of regulatory feedbacks linking the anoxic biosphere and the coupled H, C and Fe cycles. We suggest that similar processes should be considered when assessing the potential for sustained habitability on Earth-like planets with reducing atmospheres., Comment: Accepted to Nature Geoscience; Final article and Supplementary Information available at https://www.nature.com/articles/s41561-017-0031-2

Background/Aims: Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146). Methods: We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation. Results: IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production. Conclusion: IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells.

The global silica cycle is an important component of the long-term climate system, yet its controlling factors are largely uncertain due to poorly constrained proxy records. Here we present a ∼70 Myr-long record of early Mesozoic biogenic silica (BSi) flux from radiolarian chert in Japan. Average low-mid-latitude BSi burial flux in the superocean Panthalassa is ∼90% of that of the modern global ocean and relative amplitude varied by ∼20–50% over the 100 kyr to 30 Myr orbital cycles during the early Mesozoic. We hypothesize that BSi in chert was a major sink for oceanic dissolved silica (DSi), with fluctuations proportional to DSi input from chemical weathering on timescales longer than the residence time of DSi (, While the global silica cycle is known to play an important role in long-term climate change, the driving factors remain unknown. Here, the authors present a ∼70 million year long record of early Mesozoic biogenic silica and propose orbitally-paced chemical weathering as a primary driver.

The macronutrient phosphorus is thought to limit primary productivity in the oceans on geological timescales. Although there has been a sustained effort to reconstruct the dynamics of the phosphorus cycle over the past 3.5 billion years, it remains uncertain whether phosphorus limitation persisted throughout Earth's history and therefore whether the phosphorus cycle has consistently modulated biospheric productivity and ocean-atmosphere oxygen levels over time. Here we present a compilation of phosphorus abundances in marine sedimentary rocks spanning the past 3.5 billion years. We find evidence for relatively low authigenic phosphorus burial in shallow marine environments until about 800 to 700 million years ago. Our interpretation of the database leads us to propose that limited marginal phosphorus burial before that time was linked to phosphorus biolimitation, resulting in elemental stoichiometries in primary producers that diverged strongly from the Redfield ratio (the atomic ratio of carbon, nitrogen and phosphorus found in phytoplankton). We place our phosphorus record in a quantitative biogeochemical model framework and find that a combination of enhanced phosphorus scavenging in anoxic, iron-rich oceans and a nutrient-based bistability in atmospheric oxygen levels could have resulted in a stable low-oxygen world. The combination of these factors may explain the protracted oxygenation of Earth's surface over the last 3.5 billion years of Earth history. However, our analysis also suggests that a fundamental shift in the phosphorus cycle may have occurred during the late Proterozoic eon (between 800 and 635 million years ago), coincident with a previously inferred shift in marine redox states, severe perturbations to Earth's climate system, and the emergence of animals.

Gomisin N, which is a lignan isolated from Schisandra chinensis, has some pharmacological effects. However, the anti-inflammatory effects of gomisin N on periodontal disease are uncertain. The aim of this study was to examine the effect of gomisin N on inflammatory mediator production in tumor necrosis factor (TNF)-α-stimulated human periodontal ligament cells (HPDLC). Gomisin N inhibited interleukin (IL)-6, IL-8, CC chemokine ligand (CCL) 2, and CCL20 production in TNF-α-stimulated HPDLC in a dose-dependent manner. Moreover, we revealed that gomisin N could suppress extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) phosphorylation in TNF-α-stimulated HPDLC though protein kinase B (Akt) phosphorylation was not suppressed by gomisin N treatment. In summary, gomisin N might exert anti-inflammatory effects by attenuating cytokine production in periodontal ligament cells via inhibiting the TNF-α-stimulated ERK and JNK pathways activation.

Objective: Porphyromonas gingivalis (P. gingivalis) is a pathogen involved in periodontal disease. Recently, periodontal disease has been demonstrated to increase the risk of developing diabetes mellitus, although the molecular mechanism is not fully understood. Forkhead box protein O1 (FoxO1) is a transcriptional factor that regulates gluconeogenesis in the liver. Gluconeogenesis is a key process in the induction of diabetes mellitus; however, little is known regarding the relationship between periodontal disease and gluconeogenesis. In this study, to investigate whether periodontal disease influences hepatic gluconeogenesis, we examined the effects of P. gingivalis on the phosphorylation and translocation of FoxO1 in insulin-induced human hepatocytes. Design: The human hepatocyte HepG2 was treated with insulin and Akt and FoxO1 phosphorylation was detected by western blot analysis. The localization of phosphorylated FoxO1 was detected by immunocytochemistry and western blot analysis. HepG2 cells were treated with SNAP26b-tagged P. gingivalis (SNAP-P. g.) before insulin stimulation, and then the changes in Akt and FoxO1 were determined by western blot analysis and immunocytochemistry. Results: Insulin (100 nM) induced FoxO1 phosphorylation 60 min after treatment in HepG2 cells. Phosphorylated FoxO1 translocated to the cytoplasm. SNAP-P.g. internalized into HepG2 cells and decreased Akt and FoxO1 phosphorylation induced by insulin. The effect of insulin on FoxO1 translocation was also attenuated by SNAP-P.g. Conclusions: Our study shows that P. gingivalis decreases the phosphorylation and translocation of FoxO induced by insulin in HepG2 cells. Our results suggest that periodontal disease may increase hepatic gluconeogenesis by reducing the effects of insulin on FoxO1.

Silicon photomultipliers (SiPMs) have a low radioactivity, compact geometry, low operation voltage, and reasonable photo-detection efficiency for vacuum ultraviolet light (VUV). Therefore it has the potential to replace photomultiplier tubes (PMTs) for future dark matter experiments with liquid xenon (LXe). However, SiPMs have nearly two orders of magnitude higher dark count rate (DCR) compared to that of PMTs at the LXe temperature ($\sim$ 165 K). This type of high DCR mainly originates from the carriers that are generated by band-to-band tunneling effect. To suppress the tunneling effect, we have developed a new SiPM with lowered electric field strength in cooperation with Hamamatsu Photonics K. K. and characterized its performance in a temperature range of 153 K to 298 K. We demonstrated that the newly developed SiPMs had 6--54 times lower DCR at low temperatures compared to that of the conventional SiPMs., 9 pages,13 figures, 2 tables

Chronic inflammation caused by infections has been suggested to be one of the most important cause of cancers. It has recently been shown that there is correlation between intestinal bacteria and cancer development including metastasis. As over 700 bacterial species exist in an oral cavity, it has been concerning that bacterial infection may cause oral cancer. However, the role of bacteria regarding tumorigenesis of oral cancer remains unclear. Several papers have shown that Fusobacterium species deriving the oral cavities, especially, play a crucial role for the development of colorectal and esophageal cancer. F. nucleatum is a well-known oral bacterium involved in formation of typical dental plaque on human teeth and causing periodontal diseases. The greatest characteristic of F. nucleatum is its ability to adhere to various bacteria and host cells. Interestingly, F. nucleatum is frequently detected in oral cancer tissues. Moreover, detection of F. nucleatum is correlated with the clinical stage of oral cancer. Although the detailed mechanism is still unclear, Fusobacterium species have been suggested to be associated with cell adhesion, tumorigenesis, epithelial-to-mesenchymal transition, inflammasomes, cell cycle, etc. in oral cancer. In this review, we introduce the reports focused on the association of Fusobacterium species with cancer development and progression including oral, esophageal, and colon cancers.

Some atmospheric gases have been proposed as counter indicators to the presence of life on an exoplanet if remotely detectable at sufficient abundance (i.e., antibiosignatures), informing the search for biosignatures and potentially fingerprinting uninhabited habitats. However, the quantitative extent to which putative antibiosignatures could exist in the atmospheres of inhabited planets is not well understood. The most commonly referenced potential antibiosignature is CO, because it represents a source of free energy and reduced carbon that is readily exploited by life on Earth and is thus often assumed to accumulate only in the absence of life. Yet, biospheres actively produce CO through biomass burning, photooxidation processes, and release of gases that are photochemically converted into CO in the atmosphere. We demonstrate with a 1D ecosphere-atmosphere model that reducing biospheres can maintain CO levels of ~100 ppmv even at low H2 fluxes due to the impact of hybrid photosynthetic ecosystems. Additionally, we show that photochemistry around M dwarf stars is particularly favorable for the buildup of CO, with plausible concentrations for inhabited, oxygen-rich planets extending from hundreds of ppm to several percent. Since CH4 buildup is also favored on these worlds, and because O2 and O3 are likely not detectable with the James Webb Space Telescope, the presence of high CO (>100 ppmv) may discriminate between oxygen-rich and reducing biospheres with near-future transmission observations. These results suggest that spectroscopic detection of CO can be compatible with the presence of life and that a comprehensive contextual assessment is required to validate the significance of potential antibiosignatures., 10 pages, 5 figures, 2 tables. Published Open Access in ApJ

Outer membrane vesicles (OMVs) are nanosized particles derived from the outer membrane of gram-negative bacteria. Oral bacterium Porphyromonas gingivalis (Pg) is known to be a major pathogen of periodontitis that contributes to the progression of periodontal disease by releasing OMVs. The effect of Pg OMVs on systemic diseases is still unknown. To verify whether Pg OMVs affect the progress of diabetes mellitus, we analyzed the cargo proteins of vesicles and evaluated their effect on hepatic glucose metabolism. Here, we show that Pg OMVs were equipped with Pg-derived proteases gingipains and translocated to the liver in mice. In these mice, the hepatic glycogen synthesis in response to insulin was decreased, and thus high blood glucose levels were maintained. Pg OMVs also attenuated the insulin-induced Akt/glycogen synthase kinase-3 β (GSK-3β) signaling in a gingipain-dependent fashion in hepatic HepG2 cells. These results suggest that the delivery of gingipains mediated by Pg OMV elicits changes in glucose metabolisms in the liver and contributes to the progression of diabetes mellitus.

The OPERA experiment discovered muon neutrino into tau neutrino oscillations in appearance mode, detecting tau leptons by means of nuclear emulsion films. The apparatus was also endowed with electronic detectors with tracking capability, such as scintillator strips and resistive plate chambers. Because of its location in the underground Gran Sasso laboratory, under 3800 m.w.e., the OPERA detector has also been used as an observatory for TeV muons produced by cosmic rays in the atmosphere. In this paper the measurement of the single muon flux modulation and its correlation with the seasonal cycle of atmospheric temperature is reported. The OPERA experiment discovered muon neutrino into tau neutrino oscillations in appearance mode, detecting tau leptons by means of nuclear emulsion films. The apparatus was also endowed with electronic detectors with tracking capability, such as scintillator strips and resistive plate chambers. Because of its location, in the underground Gran Sasso laboratory, under 3800 m.w.e., the OPERA detector has also been used as an observatory for TeV muons produced by cosmic rays in the atmosphere. In this paper the measurement of the single muon flux modulation and of its correlation with the seasonal variation of the atmospheric temperature are reported.

The OPERA experiment has conclusively observed the appearance of tau neutrinos in the muon neutrino CNGS beam. Exploiting the OPERA detector capabilities, it was possible to isolate high purity samples of $\nu_{e}$, $\nu_{\mu}$ and $\nu_{\tau}$ charged current weak neutrino interactions, as well as neutral current weak interactions. In this Letter, the full dataset is used for the first time to test the three-flavor neutrino oscillation model and to derive constraints on the existence of a light sterile neutrino within the framework of the $3+1$ neutrino model. For the first time, tau and electron neutrino appearance channels are jointly used to test the sterile neutrino hypothesis. A significant fraction of the sterile neutrino parameter space allowed by LSND and MiniBooNE experiments is excluded at 90% C.L. In particular, the best-fit values obtained by MiniBooNE combining neutrino and antineutrino data are excluded at 3.3 $\sigma$ significance., Comment: 7 pages, 4 figures; Editors: Budimir Kli\v{c}ek and Matteo Tenti

The possibility of low but nontrivial atmospheric oxygen (O2) levels during the mid-Proterozoic (between 1.8 and 0.8 billion years ago, Ga) has important ramifications for understanding Earth's O2 cycle, the evolution of complex life and evolving climate stability. However, the regulatory mechanisms and redox fluxes required to stabilize these O2 levels in the face of continued biological oxygen production remain uncertain. Here, we develop a biogeochemical model of the C-N-P-O2-S cycles and use it to constrain global redox balance in the mid-Proterozoic ocean-atmosphere system. By employing a Monte Carlo approach bounded by observations from the geologic record, we infer that the rate of net biospheric O2 production was 3.5 (+1.4 - 1.1) Tmol year-1 (1-sigma), or ~25% of today's value, owing largely to phosphorus scarcity in the ocean interior. Pyrite burial in marine sediments would have represented a comparable or more significant O2 source than organic carbon burial, implying a potentially important role for Earth's sulphur cycle in balancing the oxygen cycle and regulating atmospheric O2 levels. Our statistical approach provides a uniquely comprehensive view of Earth system biogeochemistry and global O2 cycling during mid-Proterozoic time and implicates severe P biolimitation as the backdrop for Precambrian geochemical and biological evolution., Accepted to Geobiology; Final article and Supplementary Information available at https://onlinelibrary.wiley.com/doi/full/10.1111/gbi.12317

OPERA is a long-baseline experiment designed to search for $\nu_{\mu}\to\nu_{\tau}$ oscillations in appearance mode. It was based at the INFN Gran Sasso laboratory (LNGS) and took data from 2008 to 2012 with the CNGS neutrino beam from CERN. After the discovery of $\nu_\tau$ appearance in 2015, with $5.1\sigma$ significance, the criteria to select $\nu_\tau$ candidates have been extended and a multivariate approach has been used for events identification. In this way the statistical uncertainty in the measurement of the oscillation parameters and of $\nu_\tau$ properties has been improved. Results are reported., Comment: 7 pages, 1 figure, conference: The 15th International Workshop on Tau Lepton Physics (tau2018)AB

Objectives The biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymers, which mimic a biomembrane, reduce protein adsorption and bacterial adhesion and inhibit cell attachment. The aim of this study is to clarify whether MPC-polymer can suppress the bacterial adherence in oral cavity by a crossover design. We also investigated the number of Fusobacterium nucleatum, which is the key bacterium forming dental plaque, in clinical samples. Materials and methods This study was a randomized, placebo-controlled, single-blind, crossover study, with two treatment periods separated by a 2-week washout period. We conducted clinical trial with 20 healthy subjects to evaluate the effect of 5% MPC-polymer mouthwash after 5 h on oral microflora. PBS was used as a control. The bacterial number in the gargling sample before and after intervention was counted by an electronic bacterial counter and a culture method. DNA amounts of total bacteria and F. nucleatum were examined by q-PCR. Results The numbers of total bacteria and oral streptcocci after 5 h of 5% MPC-polymer treatment significantly decreased, compared to the control group. Moreover, the DNA amounts of total bacteria and F. nucleatum significantly decreased by 5% MPC-polymer mouthwash. Conclusions We suggest that MPC-polymer coating in the oral cavity may suppress the oral bacterial adherence. Clinical relevance MPC-polymer can be a potent compound for the control of oral microflora to prevent oral infection.