Возраст грязевой брекчии грязев ых вулканов Академического хреб та озера Байка

Lake Baikal is the only freshwater reservoir on Earth with gas-hydrate accumulations in its bottom sediments, partly due to the activity of mud volcanoes. This paper describes a group of mud volcanoes recently discovered on the slope of the Academician Ridge between the northern and central Lake Baikal basins. Our analysis of diatom skeletons in the mud breccia sampled from the study area shows a high abundance of Cyclotella iris et var. These extinct species were also discovered in a core sample from BDP-98 borehole. Based on the biostratigraphic and seis-mostratigraphic correlations, the age of the mud breccia in the studied mud volcanoes ranges from the Late Miocene to the Early Pliocene (4.6 to 5.6 Ma). The correlations suggest that the material originated from a depth of less than 310 m below the lake bottom

The Cosmic Microwave Background and Particle Physics

In forthcoming years, connections between cosmology and particle physics will be made increasingly important with the advent of a new generation of cosmic microwave background (CMB) experiments. Here, we review a number of these links. Our primary focus is on new CMB tests of inflation. We explain how the inflationary predictions for the geometry of the Universe and primordial density perturbations will be tested by CMB temperature fluctuations, and how the gravitational waves predicted by inflation can be pursued with the CMB polarization. The CMB signatures of topological defects and primordial magnetic fields from cosmological phase transitions are also discussed. Furthermore, we review current and future CMB constraints on various types of dark matter (e.g. massive neutrinos, weakly interacting massive particles, axions, vacuum energy), decaying particles, the baryon asymmetry of the Universe, ultra-high-energy cosmic rays, exotic cosmological topologies, and other new physics.Comment: 43 pages. To appear in Annual Reviews of Nuclear and Particle Scienc

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Gravity modes as a way to distinguish between hydrogen- and helium-burning red giant stars

Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained with the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly about 50 seconds) and those that are also burning helium (period spacing about 100 to 300 seconds).Comment: to appear as a Letter to Natur

Oxygen isotope heterogeneity of the mantle beneath the Canary Islands : insights from olivine phenocrysts

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 162 (2011): 349-363, doi:10.1007/s00410-010-0600-5.A relatively narrow range of oxygen isotopic ratios (δ18O = 5.05.4‰) is preserved in olivine of mantle xenoliths, mid-ocean ridge (MORB) and most ocean island basalts (OIB). The values in excess of this range are generally attributed either to the presence of a recycled component in the Earth’s mantle or to shallow level contamination processes. A viable way forward to trace source heterogeneity is to find a link between chemical (elemental and isotopic) composition of the earlier crystallized mineral phases (olivine) and the composition of their parental magmas, then using them to reconstruct the composition of source region. The Canary hotspot is one of a few that contains ~1-2 Ga old recycled ocean crust that can be traced to the core-mantle boundary using seismic tomography and whose origin is attributed to the mixing of at least three main isotopically distinct mantle components i.e., HIMU, DMM and EM. This work reports ion microprobe and single crystal laser fluorination oxygen isotope data of 148 olivine grains also analyzed for major and minor elements in the same spot. The olivines are from 20 samples resembling the most primitive shield stage picrite through alkali basalt to basanite series erupted on Gran Canaria, Tenerife, La Gomera, La Palma and El Hierro, Canary Islands, for which shallow level contamination processes were not recognized. A broad range of δ18Oolivine values from 4.6 to 6.1‰ was obtained and explained by stable, long-term oxygen isotope heterogeneity of crystal cumulates present under different volcanoes. These cumulates are thought to have crystallized from mantle derived magmas uncontaminated at crustal depth, representing oxygen isotope heterogeneity of source region. A relationship between Ni×FeO/MgO and δ18Oolivine values found in one basanitic lava erupted on El Hierro, the westernmost island of the Canary Archipelago, was used to estimate oxygen isotope compositions of partial melts presumably originated from peridotite (HIMU-type component inherited its radiogenic isotope composition from ancient, ~12 Ga, recycled ocean crust) and pyroxenite (young, <1 Ga, recycled oceanic crust preserved as eclogite with depleted MORB-type isotopic signature) components of the Canary plume. The model calculations yield 5.2 and 5.9±0.3‰ for peridotite and pyroxenite derived melts, respectively, which appeared to correspond closely to the worldwide HIMU-type OIB and upper limit N-MORB δ18O values. This difference together with the broad range of δ18O variations found in the Canarian olivines cannot be explained by thermodynamic effects of oxygen isotopic fractionation and are believed to represent true variations in the mantle, due to oceanic crust and continental lithosphere recycling.This work was supported by the CNRS “poste rouge” grant to AG, the NSF EAR-CAREER-0844772 grant to IB and the CRPG-CNRS and at its initial stage by the DFG (grant SCHM 250/64) and the Alexander von Humboldt Foundation (Wolfgang Paul Award to A.V. Sobolev who provided access to the electron microprobe at the Max Planck Institute, Mainz, Germany)

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Ab-Externo AAV-Mediated Gene Delivery to the Suprachoroidal Space Using a 250 Micron Flexible Microcatheter

The current method of delivering gene replacement to the posterior segment of the eye involves a three-port pars plana vitrectomy followed by injection of the agent through a 37-gauge cannula, which is potentially wrought with retinal complications. In this paper we investigate the safety and efficacy of delivering adeno-associated viral (AAV) vector to the suprachoroidal space using an ab externo approach that utilizes an illuminated microcatheter.6 New Zealand White rabbits and 2 Dutch Belted rabbits were used to evaluate the ab externo delivery method. sc-AAV5-smCBA-hGFP vector was delivered into the suprachoroidal space using an illuminated iTrackTM 250A microcatheter. Six weeks after surgery, the rabbits were sacrificed and their eyes evaluated for AAV transfection using immunofluorescent antibody staining of GFP.Immunostaining of sectioned and whole-mounted eyes demonstrated robust transfection in all treated eyes, with no fluorescence in untreated control eyes. Transfection occurred diffusely and involved both the choroid and the retina. No apparent adverse effects caused by either the viral vector or the procedure itself could be seen either clinically or histologically.The ab externo method of delivery using a microcatheter was successful in safely and effectively delivering a gene therapy agent to the suprachoroidal space. This method presents a less invasive alternative to the current method of virally vectored gene delivery

Circular Permutation in the Ω-Loop of TEM-1 β-Lactamase Results in Improved Activity and Altered Substrate Specificity

Generating diverse protein libraries that contain improved variants at a sufficiently high frequency is critical for improving the properties of proteins using directed evolution. Many studies have illustrated how random mutagenesis, cassette mutagenesis, DNA shuffling and similar approaches are effective diversity generating methods for directed evolution. Very few studies have explored random circular permutation, the intramolecular relocation of the N- and C-termini of a protein, as a diversity-generating step for directed evolution. We subjected a library of random circular permutations of TEM-1 β-lactamase to selections on increasing concentrations of a variety of β-lactam antibiotics including cefotaxime. We identified two circularly permuted variants that conferred elevated resistance to cefotaxime but decreased resistance to other antibiotics. These variants were circularly permuted in the Ω-loop proximal to the active site. Remarkably, one variant was circularly permuted such that the key catalytic residue Glu166 was located at the N-terminus of the mature protein

Shortcomings of Vitamin D-Based Model Simulations of Seasonal Influenza

Seasonal variation in serum concentration of the vitamin D metabolite 25(OH) vitamin D [25(OH)D], which contributes to host immune function, has been hypothesized to be the underlying source of observed influenza seasonality in temperate regions. The objective of this study was to determine whether observed 25(OH)D levels could be used to simulate observed influenza infection rates. Data of mean and variance in 25(OH)D serum levels by month were obtained from the Health Professionals Follow-up Study and used to parameterize an individual-based model of influenza transmission dynamics in two regions of the United States. Simulations were compared with observed daily influenza excess mortality data. Best-fitting simulations could reproduce the observed seasonal cycle of influenza; however, these best-fit simulations were shown to be highly sensitive to stochastic processes within the model and were unable consistently to reproduce observed seasonal patterns. In this respect the simulations with the vitamin D forced model were inferior to similar modeling efforts using absolute humidity and the school calendar as seasonal forcing variables. These model results indicate it is unlikely that seasonal variations in vitamin D levels principally determine the seasonality of influenza in temperate regions