76 research outputs found
Rapid Glacial Erosion at 1.8 Ma Revealed by ^4He/^3He Thermochronometry
Alpine glaciation and river incision control the topography of mountain ranges, but their relative contributions have been debated for years. Apatite ^(4)He/^(3)He thermochronometry tightly constrains the timing and rate of glacial erosion within one of the largest valleys in the southern Coast Mountains of British Columbia, Canada. Five proximate samples require accelerated denudation of the Klinaklini Valley initiating 1.8 ± 0.2 million years ago (Ma). At least 2 kilometers of overlying rock were removed from the valley at ≥5 millimeters per year, indicating that glacial valley deepening proceeded ≥6 times as fast as erosion rates before ∼1.8 Ma. This intense erosion may be related to a global transition to enhanced climate instability ∼1.9 Ma
Nanotools for Neuroscience and Brain Activity Mapping
Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function
Brazilian Consensus on Photoprotection
Brazil is a country of continental dimensions with a large heterogeneity of climates and massive mixing of the population. Almost the entire national territory is located between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the south certainly makes Brazil one of the countries of the world with greater extent of land in proximity to the sun. The Brazilian coastline, where most of its population lives, is more than 8,500 km long. Due to geographic characteristics and cultural trends, Brazilians are among the peoples with the highest annual exposure to the sun. Epidemiological data show a continuing increase in the incidence of nonmelanoma and melanoma skin cancers. Photoprotection can be understood as a set of measures aimed at reducing sun exposure and at preventing the development of acute and chronic actinic damage. Due to the peculiarities of Brazilian territory and culture, it would not be advisable to replicate the concepts of photoprotection from other developed countries, places with completely different climates and populations. Thus the Brazilian Society of Dermatology has developed the Brazilian Consensus on Photoprotection, the first official document on photoprotection developed in Brazil for Brazilians, with recommendations on matters involving photoprotection
Aqueous alteration processes in Jezero crater, Mars—implications for organic geochemistry
The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
^4He/^3He thermochronometry
Using classical diffusion theory, we present a mathematical technique for the determination of ^4He concentration profiles in minerals. This approach should prove useful for constraining the low-temperature cooling histories of individual samples and for correcting (U–Th)/He ages for partial diffusive loss. The calculation assumes that the mineral of interest contains an artificially produced and uniform distribution of ^3He obtained by proton irradiation [Shuster et al., Earth Planet. Sci. Lett. 217 (2004) 19–32]. In minerals devoid of natural helium, this isotope allows measurement of He diffusion coefficients; in minerals with measurable radiogenic He, it permits determination of ^4He profiles arising during ingrowth and diffusion in nature. The ^4He profile can be extracted from stepwise degassing experiments in which the ^4He/^3He ratio is measured. The evolution of the ^4He/^3He ratio as a function of cumulative ^3He released can be compared with forward models to constrain the shape of the profile. Alternatively, we present a linear inversion that can be used to directly solve for the unknown ^4He distribution. The inversion incorporates a standard regularization technique to filter the influence of random measurement errors on the solution. Using either approach we show that stepwise degassing data can yield robust and high-resolution information on the ^4He profile. Profiles of radiogenic He are a sensitive function of the time–Temperate (t–T) path that a cooling sample experienced. Thus, by step heating a proton-irradiated sample it is possible to restrict the sample’s acceptable t–T paths. The sensitivity of this approach was explored by forward-modeling ^4He profiles resulting from a range of realistic t–T paths, using apatite as an example. Results indicate that ^4He profiles provide rich information on t–T paths, especially when the profiles are coupled with (U–Th)/He cooling ages on the same sample. Samples that experienced only moderate diffusive loss have ^4He concentration profiles that are rounded at the edge but uniform in the core of the diffusion domain. Such profiles can be identified by nearly invariant ^4He/^3He ratios after the first few to few tens of percent of ^3He have been extracted by step heating. We show how such data can be used to correct (U–Th)/He ages for partial diffusive loss
Diffusion kinetics of proton-induced ^(21)Ne, ^3He, and ^4He in quartz
A natural quartz sample free of mineral and fluid inclusions was irradiated with a 200 MeV proton beam to produce spallogenic ^(21)Ne, ^3He and ^4He. Temperature-dependent diffusivities of these three nuclides were then determined simultaneously by high precision stepped-heating and noble gas mass spectrometry. The outward mobility of proton-induced nuclides reflects diffusion through the quartz lattice. In the studied range of 70 to 400°C the helium diffusion coefficients exceed those of neon by 5–7 orders of magnitude. The implied diffusion parameters E_a = 153.7 ± 1.5 (kJ/mol) and ln(D_o/a^2) = 15.9 ± 0.3 (ln(s^(−1))) and E_a = 84.5 ± 1.2 (kJ/mol) and ln(D_o/a^2) = 11.1 ± 0.3 (ln(s^(−1))) for proton-induced ^(21)Ne and ^3He, respectively, indicate that cosmogenic neon will be quantitatively retained in inclusion-free quartz at typical Earth surface temperatures whereas cosmogenic helium will not. However, the neon diffusion parameters also indicate that diffusive loss needs to be considered for small (<1 mm) quartz grains that have experienced elevated temperatures. Since natural quartz often contains fluid inclusions which may enhance noble gas retentivity, these parameters likely represent an end-member case of purely solid-state diffusion. The ∼70 kJ/mol higher activation energy for neon diffusion compared to helium diffusion likely represents an energy barrier related to its ∼13% greater diameter and provides a fundamental constraint with which to test theories of solid state diffusion. The diffusion parameters for proton-induced ^4He are indistinguishable from those for ^3He, providing no evidence for the commonly expected inverse square root of the mass diffusion relationship between isotopes. We also find preliminary indication that increased exposure to radiation may enhance neon and helium retentivity in quartz at low temperatures
The influence of artificial radiation damage and thermal annealing on helium diffusion kinetics in apatite
Recent work [Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett. 249(3–4), 148–161] revealing a correlation between radiogenic 4He concentration and He diffusivity in natural apatites suggests that helium migration is retarded by radiation-induced damage to the crystal structure. If so, the He diffusion kinetics of an apatite is an evolving function of time and the effective uranium concentration in a cooling sample, a fact which must be considered when interpreting apatite (U–Th)/He ages. Here we report the results of experiments designed to investigate and quantify this phenomenon by determining He diffusivities in apatites after systematically adding or removing radiation damage.
Radiation damage was added to a suite of synthetic and natural apatites by exposure to between 1 and 100 h of neutron irradiation in a nuclear reactor. The samples were then irradiated with a 220 MeV proton beam and the resulting spallogenic 3He used as a diffusant in step-heating diffusion experiments. In every sample, irradiation increased the activation energy (Ea) and the frequency factor (Do/a^2) of diffusion and yielded a higher He closure temperature (Tc) than the starting material. For example, 100 h in the reactor caused the He closure temperature to increase by as much as 36 °C. For a given neutron fluence the magnitude of increase in closure temperature scales negatively with the initial closure temperature. This is consistent with a logarithmic response in which the neutron damage is additive to the initial damage present. In detail, the irradiations introduce correlated increases in Ea and ln(Do/a^2) that lie on the same array as found in natural apatites. This strongly suggests that neutron-induced damage mimics the damage produced by U and Th decay in natural apatites.
To investigate the potential consequences of annealing of radiation damage, samples of Durango apatite were heated in vacuum to temperatures up to 550 °C for between 1 and 350 h. After this treatment the samples were step-heated using the remaining natural 4He as the diffusant. At temperatures above 290 °C a systematic change in Tc was observed, with values becoming lower with increasing temperature and time. For example, reduction of Tc from the starting value of 71 to ~52 °C occurred in 1 h at 375 °C or 10 h at 330 °C. The observed variations in Tc are strongly correlated with the fission track length reduction predicted from the initial holding time and temperature. Furthermore, like the neutron irradiated apatites, these samples plot on the same Ea − ln(Do/a2) array as natural samples, suggesting that damage annealing is simply undoing the consequences of damage accumulation in terms of He diffusivity.
Taken together these data provide unequivocal evidence that at these levels, radiation damage acts to retard He diffusion in apatite, and that thermal annealing reverses the process. The data provide support for the previously described radiation damage trapping kinetic model of Shuster et al. (2006) and can be used to define a model which fully accommodates damage production and annealing
Leachate damage assessment : case study of the Peoples Avenue Solid Waste Disposal Site in Rockford, Illinois /
Item 431-I-7Includes appendix.Bibliography: p. 21.Mode of access: Internet
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