On the importance of initial conditions for simulations of the Mid-Holocene climate.

Three simulations of the Mid-Holocene (6 ka) climate were performed with the ECBilt-CLIO-VECODE coupled atmosphere-ocean-vegetation model to study the impact of initial conditions. These experiments were forced with identical 6 ka forcings (orbital parameters and atmospheric greenhouse gas concentrations) and differed only in initial conditions. Two simulations were designed as equilibrium experiments, with one being initialized with preindustrial conditions as required by the protocol of the Paleoclimate Modelling Intercomparison Project (PMIP), while in a second experiment early Holocene (9 ka) initial conditions were used. These equilibrium simulations were run for 2100 years with 6 ka forcings. The third experiment was set up as a transient simulation, also starting from early Holocene conditions, but forced with annually changing orbital parameters and greenhouse gas levels. The results of the last 100 years are compared and reveal no statistically significant differences, showing that in this model the initial conditions have no discernible impact on the 6 ka climate. This suggests that the PMIP set-up for 6 ka simulations is valid, with the condition that spin-up phase should be long enough (at least 550 years) to allow the deep ocean to adjust to the change in forcings

The Eurasian ice sheet reinforces the East Asian summer monsoon during the interglacial 500 000 years ago

Deep-sea and ice-core records show that interglacial periods were overall less "warm" before about 420 000 years ago than after, with relatively higher ice volume and lower greenhouse gases concentration. This is particularly the case for the interglacial Marine Isotope Stage 13 which occurred about 500 000 years ago. However, by contrast, the loess and other proxy records from China suggest an exceptionally active East Asian summer monsoon during this interglacial. A three-dimension Earth system Model of Intermediate complexity was used to understand this seeming paradox. The astronomical forcing and the remnant ice sheets present in Eurasia and North America were taken into account in a series of sensitivity experiments. Expectedly, the seasonal contrast is larger and the East Asian summer monsoon is reinforced compared to Pre-Industrial time when Northern Hemisphere summer is at perihelion. Surprisingly, the presence of the Eurasian ice sheet was found to reinforce monsoon, too, through a south-eastwards perturbation planetary wave. The trajectory of this wave is influenced by the Tibetan plateau

Modelling the climate of the last millennium: what causes the differences between simulations?

An ensemble of simulations performed with a coarse resolution 3-D climate model driven by various combinations of external forcing is used to investigate possible causes for differences noticed in two recent simulations of the climate of the past millennium using General Circulation Models (GCMs). Our results strongly suggest that differences in sensitivity (equilibrium and transient climate response) could be responsible for temperature changes that differ by more than a factor of two between two models. In addition, the spin-up procedure could explain some differences between the simulations during the first centuries of the second millennium. The choice of the forcing reconstruction is found to play a smaller role for the differences in the simulated climate, in the model configurations analyzed here. Furthermore, at decadal scale, internal climate variability can mask the differences associated with different forcing reconstructrions. Copyright 2005 by the American Geophysical Union

Cleavage-Resistant Protein Labeling With Hydrophilic Trityl Enables Distance Measurements In-Cell.

Sensitive in-cell distance measurements in proteins using pulsed-electron spin resonance (ESR) require reduction-resistant and cleavage-resistant spin labels. Among the reduction-resistant moieties, the hydrophilic trityl core known as OX063 is promising due to its long phase-memory relaxation time (Tm). This property leads to a sufficiently intense ESR signal for reliable distance measurements. Furthermore, the Tm of OX063 remains sufficiently long at higher temperatures, opening the possibility for measurements at temperatures above 50 K. In this work, we synthesized deuterated OX063 with a maleimide linker (mOX063-d24). We show that the combination of the hydrophilicity of the label and the maleimide linker enables high protein labeling that is cleavage-resistant in-cells. Distance measurements performed at 150 K using this label are more sensitive than the measurements at 80 K. The sensitivity gain is due to the significantly short longitudinal relaxation time (T1) at higher temperatures, which enables more data collection per unit of time. In addition to in vitro experiments, we perform distance measurements in Xenopus laevis oocytes. Interestingly, the Tm of mOX063-d24 is sufficiently long even in the crowded environment of the cell, leading to signals of appreciable intensity. Overall, mOX063-d24 provides highly sensitive distance measurements both in vitro and in-cells

Nitro-Triarylmethyl Radical as Dual Oxygen and Superoxide Probe

Superoxide radical is involved in numerous physiological and pathophysiological processes. Tetrathiatriarylmethyl (TAM) radicals are knows to react with superoxide allowing measurement of superoxide production in biological media. We report the synthesis of a Nitro conjugated TAM radical showing a rate constant of 7 × 105 M−1s−1 which is two order of magnitude higher than other TAMs allowing high sensitivity measurement of superoxid

Nitro-Triarylmethyl Radical as Dual Oxygen and Superoxide Probe

Superoxide radical is involved in numerous physiological and pathophysiological processes. Tetrathiatriarylmethyl (TAM) radicals are knows to react with superoxide allowing measurement of superoxide production in biological media. We report the synthesis of a Nitro conjugated TAM radical showing a rate constant of 7 × 105 M−1s−1 which is two order of magnitude higher than other TAMs allowing high sensitivity measurement of superoxid

Observing Nearby Nuclei on Paramagnetic Trityls and MOFs via DNP and Electron Decoupling

Dynamic nuclear polarization (DNP) is an NMR sensitivity enhancement technique that mediates polarization transfer from unpaired electrons to NMR-active nuclei. Despite its success in elucidating important structural information on biological and inorganic materials, the detailed polarization-transfer pathway from the electrons to the nearby and then the bulk solvent nuclei, and finally to the molecules of interest-remains unclear. In particular, the nuclei in the paramagnetic polarizing agent play significant roles in relaying the enhanced NMR polarizations to more remote nuclei. Despite their importance, the direct NMR observation of these nuclei is challenging because of poor sensitivity. Here, we show that a combined DNP and electron decoupling approach can facilitate direct NMR detection of these nuclei. We achieved an ∼80 % improvement in NMR intensity via electron decoupling at 0.35 T and 80 K on trityl radicals. Moreover, we recorded a DNP enhancement factor of urn:x-wiley:09476539:media:chem202202556:chem202202556-math-0001 ∼90 and ∼11 % higher NMR intensity using electron decoupling on paramagnetic metal-organic framework, magnesium hexaoxytriphenylene (MgHOTP MOF)

Development of Multifunctional Overhauser-enhanced Magnetic Rresonance Imaging for Concurrent in Vivo Mapping of Tumor Interstitial Oxygenation, Acidosis and Inorganic Phosphate Concentration

Tumor oxygenation (pO2), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, pO2, and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of breast cancer. Tumor tissues showed higher heterogeneity of the distributions of the parameters compared with normal mammary gland and demonstrated the areas of significant acidosis, hypoxia, and elevated Pi content

Observing Nearby Nuclei on Paramagnetic Trityls and MOFs via DNP and Electron Decoupling

Dynamic nuclear polarization (DNP) is an NMR sensitivity enhancement technique that mediates polarization transfer from unpaired electrons to NMR-active nuclei. Despite its success in elucidating important structural information on biological and inorganic materials, the detailed polarization-transfer pathway-from the electrons to the nearby and then the bulk solvent nuclei, and finally to the molecules of interest-remains unclear. In particular, the nuclei in the paramagnetic polarizing agent play significant roles in relaying the enhanced NMR polarizations to more remote nuclei. Despite their importance, the direct NMR observation of these nuclei is challenging because of poor sensitivity. Here, we show that a combined DNP and electron decoupling approach can facilitate direct NMR detection of these nuclei. We achieved an ~80 % improvement in NMR intensity via electron decoupling at 0.35 T and 80 K on trityl radicals. Moreover, we recorded a DNP enhancement factor of $\epsilon$ ~ 90 and ~11 % higher NMR intensity using electron decoupling on a paramagnetic metal-organic framework, magnesium hexaoxytriphenylene (MgHOTP MOF)

Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression

Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivo concurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi], pO2, pHe and tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression