158 research outputs found
First-principles molecular-dynamics simulations of a hydrous silica melt: Structural properties and hydrogen diffusion mechanism
We use {\it ab initio} molecular dynamics simulations to study a sample of
liquid silica containing 3.84 wt.% HO.We find that, for temperatures of
3000 K and 3500 K,water is almost exclusively dissolved as hydroxyl groups, the
silica network is partially broken and static and dynamical properties of the
silica network change considerably upon the addition of water.Water molecules
or free O-H groups occur only at the highest temperature but are not stable and
disintegrate rapidly.Structural properties of this system are compared to those
of pure silica and sodium tetrasilicate melts at equivalent temperatures. These
comparisons confirm the picture of a partially broken tetrahedral network in
the hydrous liquid and suggest that the structure of the matrix is as much
changed by the addition of water than it is by the addition of the same amount
(in mole %) of sodium oxide. On larger length scales, correlations are
qualitatively similar but seem to be more pronounced in the hydrous silica
liquid. Finally, we study the diffusion mechanisms of the hydrogen atoms in the
melt. It turns out that HOSi triclusters and SiO dangling bonds play a
decisive role as intermediate states for the hydrogen diffusion.Comment: 25 pages, 18 figures. submitte
Bovine testicular [beta]-galactosidase: Purification of enzyme fractions that exhibit high affinity for phosphomannosyl receptors
An improved method is described for the preparation of bovine testicular [beta]-galactosidase that allows the isolation of enzyme fractions that bind avidly to phosphomannosyl receptors. The procedure permits removal of a contaminating [beta]-hexosaminidase and yields nearly homogeneous [beta]-galactosidase. Enzyme eluted from DEAE-Sephacel was arbitrarily divided into pools that exhibited differing ability to bind phosphomannosyl receptors. A high binding fraction was rapidly assimilated by cultured cells and bound to both low and high molecular weight phosphomannosyl receptors. Carbohydrate analysis of the high binding fraction indicates an average content of one complex and one high mannose oligosaccharide chain per molecule and an average mannose 6-phosphate content of two residues per molecule. However, electrofocusing studies indicated that all the fractions were heterogeneous with respect to sialic acid and phosphate content. The purification procedure also provides highly purified [beta]-galactosidase suitable for removing [beta]-galactosidase residues from a variety of complex carbohydrates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27707/1/0000093.pd
The planform of epeirogeny: vertical motions of Australia during the Cretaceous
Estimates of dynamic motion of Australia since the end of the Jurassic have been made by modeling marine flooding and comparing it with palaeogeographical reconstructions of marine inundation. First, sediment isopachs were back stripped from present-day topography. Dynamic motion was determined by the displacement needed to approximate observed flooding when allowance is made for changes in eustatic sea-level. The reconstructed inundation patterns suggest that during the Cretaceous, Australia remained a relatively stable platform, and flooding in the eastern interior during the Early Cretaceous was primarily the result of the regional tectonic motion. Vertical motion during the Cretaceous was much smaller than the movement since the end of the Cretaceous. Subsidence and marine flooding in the Eromanga and Surat Basins, and the subsequent 500 m of uplift of the eastern portion of the basin, may have been driven by changes in plate dynamics during the Mesozoic. Convergence along the north-east edge of Australia between 200 and 100 Ma coincides with platform sedimentation and subsidence within the Eromanga and Surat Basins. A major shift in the position of subduction at 140 Ma was coeval with the marine incursion into the Eromanga. When subduction ended at 95 Ma, marine inundation of the Eromanga also ended. Subsidence and uplift of the eastern interior is consistent with dynamic models of subduction in which subsidence is generated when the dip angle of the slab decreases and uplift is generated when subduction terminates (i.e. the dynamic load vanishes). Since the end of the Cretaceous, Australia has uniformly subsided by about 250 m with little apparent tilting. This vertical subsidence may have resulted from the northward migration of the continent from a dynamic topography high and geoid low toward lower dynamic topography and a higher geoid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71983/1/j.1365-2117.1994.tb00076.x.pd
Imagable 4T1 model for the study of late stage breast cancer
<p>Abstract</p> <p>Background</p> <p>The 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene function <it>in vivo</it>. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported.</p> <p>Methods</p> <p>The lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cells <it>in vivo</it>. Biophotonic imaging was used to characterize growth and metastasis of the lines <it>in vivo </it>and an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed.</p> <p>Results</p> <p>Growth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified.</p> <p>Conclusion</p> <p>The production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously appreciated in orchestrating changes in the tumor environment conducive to tumor cell dissemination and metastasis. The new cell lines will greatly facilitate the study of late stage breast and preclinical assessment of cancer drugs and other therapeutics particularly those targeting immune system effects on tumor metastasis.</p
Fate of water pumped from underground and contributions to sea-level rise
The contributions from terrestrial water sources to sea-level rise, other than ice caps and glaciers, are highly uncertain and heavily debated.. Recent assessments indicate that groundwater depletion (GWD) may become the most important positive terrestrial contribution over the next 50 years, probably equal in magnitude to the current contributions from glaciers and ice caps6. However, the existing estimates assume that nearly 100% of groundwater extracted eventually ends up in the oceans. Owing to limited knowledge of the pathways and mechanisms governing the ultimate fate of pumped groundwater, the relative fraction of global GWD that contributes to sea-level rise remains unknown. Here, using a coupled climate–hydrological model simulation, we show that only 80% of GWD ends up in the ocean. An increase in runoff to the ocean accounts for roughly two-thirds, whereas the remainder results from the enhanced net flux of precipitation minus evaporation over the ocean, due to increased atmospheric vapour transport from the land to the ocean. The contribution of GWD to global sea-level rise amounted to 0.02 (±0.004) mm yr−1 in 1900 and increased to 0.27 (±0.04) mm yr−1 in 2000. This indicates that existing studies have substantially overestimated the contribution of GWD to global sea-level rise by a cumulative amount of at least 10 mm during the twentieth century and early twenty-first century. With other terrestrial water contributions included, we estimate the net terrestrial water contribution during the period 1993–2010 to be +0.12 (±0.04) mm yr−1, suggesting that the net terrestrial water contribution reported in the IPCC Fifth Assessment Report report is probably overestimated by a factor of three
Imaging and imagination: understanding the endo-lysosomal system
Lysosomes are specialized compartments for the degradation of endocytosed and intracellular material and essential regulators of cellular homeostasis. The importance of lysosomes is illustrated by the rapidly growing number of human disorders related to a defect in lysosomal functioning. Here, we review current insights in the mechanisms of lysosome biogenesis and protein sorting within the endo-lysosomal system. We present increasing evidence for the existence of parallel pathways for the delivery of newly synthesized lysosomal proteins directly from the trans-Golgi network (TGN) to the endo-lysosomal system. These pathways are either dependent or independent of mannose 6-phosphate receptors and likely involve multiple exits for lysosomal proteins from the TGN. In addition, we discuss the different endosomal intermediates and subdomains that are involved in sorting of endocytosed cargo. Throughout our review, we highlight some examples in the literature showing how imaging, especially electron microscopy, has made major contributions to our understanding of the endo-lysosomal system today
The African Landscape through Space and Time
It is generally accepted that Cenozoic epeirogeny of the African continent is moderated by convective circulation of the mantle. Nevertheless, the spatial and temporal evolution of Africa's “basin-and-swell” physiography is not well known. Here we show how continental drainage networks can be used to place broad constraints on the pattern of uplift through space and time. First, we assemble an inventory of 710 longitudinal river profiles that includes major tributaries of the 10 largest catchments. River profiles have been jointly inverted to determine the pattern of uplift rate as a function of space and time. Our inverse model assumes that shapes of river profiles are controlled by uplift rate history and modulated by erosional processes, which can be calibrated using independent geologic evidence (e.g., marine terraces, volcanism and thermochronologic data). Our results suggest that modern African topography started to develop ∼30 Myr ago when volcanic swells appeared in North and East Africa. During the last 15–20 Myr, subequatorial Africa was rapidly elevated, culminating in the appearance of three large swells that straddle southern and western coasts. Our results enable patterns of sedimentary flux at major deltas to be predicted and tested. We suggest that the evolution of drainage networks is dominated by rapid upstream advection of signals produced by a changing pattern of regional uplift. An important corollary is that, with careful independent calibration, these networks might act as useful tape recorders of otherwise inaccessible mantle processes. Finally, we note that there are substantial discrepancies between our results and published dynamic topographic predictions
An uplift history of the Colorado Plateau and its surroundings from inverse modeling of longitudinal river profiles
Earth: Atmospheric Evolution of a Habitable Planet
Our present-day atmosphere is often used as an analog for potentially
habitable exoplanets, but Earth's atmosphere has changed dramatically
throughout its 4.5 billion year history. For example, molecular oxygen is
abundant in the atmosphere today but was absent on the early Earth. Meanwhile,
the physical and chemical evolution of Earth's atmosphere has also resulted in
major swings in surface temperature, at times resulting in extreme glaciation
or warm greenhouse climates. Despite this dynamic and occasionally dramatic
history, the Earth has been persistently habitable--and, in fact,
inhabited--for roughly 4 billion years. Understanding Earth's momentous changes
and its enduring habitability is essential as a guide to the diversity of
habitable planetary environments that may exist beyond our solar system and for
ultimately recognizing spectroscopic fingerprints of life elsewhere in the
Universe. Here, we review long-term trends in the composition of Earth's
atmosphere as it relates to both planetary habitability and inhabitation. We
focus on gases that may serve as habitability markers (CO2, N2) or
biosignatures (CH4, O2), especially as related to the redox evolution of the
atmosphere and the coupled evolution of Earth's climate system. We emphasize
that in the search for Earth-like planets we must be mindful that the example
provided by the modern atmosphere merely represents a single snapshot of
Earth's long-term evolution. In exploring the many former states of our own
planet, we emphasize Earth's atmospheric evolution during the Archean,
Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of
potential atmospheric trajectories into the distant future, many millions to
billions of years from now. All of these 'Alternative Earth' scenarios provide
insight to the potential diversity of Earth-like, habitable, and inhabited
worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook
of Exoplanet
Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis
Metastasis remains a leading cause of cancer mortality due to the lack of specific inhibitors against this complex process. To identify compounds selectively targeting the metastatic state, we used the perinuclear compartment (PNC), a complex nuclear structure associated with metastatic behaviors of cancer cells, as a phenotypic marker for a high-content screen of over 140,000 structurally diverse compounds. Metarrestin, obtained through optimization of a screening hit, disassembles PNCs in multiple cancer cell lines, inhibits invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects. Metarrestin disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, at least in part by interacting with the translation elongation factor eEF1A2. Thus, metarrestin represents a potential therapeutic approach for the treatment of metastatic cancer
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