560 research outputs found
Understanding high pressure hydrogen with a hierarchical machine-learned potential
The hydrogen phase diagram has a number of unusual features which are
generally well reproduced by density functional calculations. Unfortunately,
these calculations fail to provide good physical insights into why those
features occur. In this paper, we parameterize a model potential for molecular
hydrogen which permits long and large simulations. The model shows excellent
reproduction of the phase diagram, including the broken-symmetry Phase II, an
efficiently-packed phase III and the maximum in the melt curve. It also gives
an excellent reproduction of the vibrational frequencies, including the maximum
in the vibrational frequency and negative thermal expansion. By
detailed study of lengthy molecular dynamics, we give intuitive explanations
for observed and calculated properties. All solid structures approximate to
hexagonal close packed, with symmetry broken by molecular orientation. At high
pressure, Phase I shows significant short-ranged correlations between molecular
orientations. The turnover in Raman frequency is due to increased coupling
between neighboring molecules, rather than weakening of the bond. The liquid is
denser than the close-packed solid because, at molecular separations below
2.3\AA, the favoured relative orientation switches from
quadrupole-energy-minimising to steric-repulsion-minimising. The latter allows
molecules to get closer together, without atoms getting closer but this cannot
be achieved within the constraints of a close-packed layer
Variational Methods for Biomolecular Modeling
Structure, function and dynamics of many biomolecular systems can be
characterized by the energetic variational principle and the corresponding
systems of partial differential equations (PDEs). This principle allows us to
focus on the identification of essential energetic components, the optimal
parametrization of energies, and the efficient computational implementation of
energy variation or minimization. Given the fact that complex biomolecular
systems are structurally non-uniform and their interactions occur through
contact interfaces, their free energies are associated with various interfaces
as well, such as solute-solvent interface, molecular binding interface, lipid
domain interface, and membrane surfaces. This fact motivates the inclusion of
interface geometry, particular its curvatures, to the parametrization of free
energies. Applications of such interface geometry based energetic variational
principles are illustrated through three concrete topics: the multiscale
modeling of biomolecular electrostatics and solvation that includes the
curvature energy of the molecular surface, the formation of microdomains on
lipid membrane due to the geometric and molecular mechanics at the lipid
interface, and the mean curvature driven protein localization on membrane
surfaces. By further implicitly representing the interface using a phase field
function over the entire domain, one can simulate the dynamics of the interface
and the corresponding energy variation by evolving the phase field function,
achieving significant reduction of the number of degrees of freedom and
computational complexity. Strategies for improving the efficiency of
computational implementations and for extending applications to coarse-graining
or multiscale molecular simulations are outlined.Comment: 36 page
Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay
The decay channel
is studied using a sample of events collected
by the BESIII experiment at BEPCII. A strong enhancement at threshold is
observed in the invariant mass spectrum. The enhancement can be fit
with an -wave Breit-Wigner resonance function with a resulting peak mass of
and a
narrow width that is at the 90% confidence level.
These results are consistent with published BESII results. These mass and width
values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics
ATP Enhances Spontaneous Calcium Activity in Cultured Suburothelial Myofibroblasts of the Human Bladder
BACKGROUND: Suburothelial myofibroblasts (sMF) are located underneath the urothelium in close proximity to afferent nerves. They express purinergic receptors and show calcium transients in response to ATP. Therefore they are supposed to be involved in afferent signaling of the bladder fullness. Since ATP concentration is likely to be very low during the initial filling phase, we hypothesized that sMF Ca(2+) activity is affected even at very low ATP concentrations. We investigated ATP induced modulation of spontaneous activity, intracellular calcium response and purinergic signaling in cultured sMF. METHODOLOGY/PRINCIPAL FINDINGS: Myofibroblast cultures, established from cystectomies, were challenged by exogenous ATP in presence or absence of purinergic antagonist. Fura-2 calcium imaging was used to monitor ATP (10(-16) to 10(-4) mol/l) induced alterations of calcium activity. Purinergic receptors (P2X1, P2X2, P2X3) were analysed by confocal immunofluorescence. We found spontaneous calcium activity in 55.18% ± 1.65 of the sMF (N = 48 experiments). ATP significantly increased calcium activity even at 10(-16) mol/l. The calcium transients were partially attenuated by subtype selective antagonist (TNP-ATP, 1 µM; A-317491, 1 µM), and were mimicked by the P2X1, P2X3 selective agonist α,β-methylene ATP. The expression of purinergic receptor subtypes in sMF was confirmed by immunofluorescence. CONCLUSIONS/SIGNIFICANCE: Our experiments demonstrate for the first time that ATP can modulate spontaneous activity and induce intracellular Ca(2+) response in cultured sMF at very low concentrations, most likely involving P2X receptors. These findings support the notion that sMF are able to register bladder fullness very sensitively, which predestines them for the modulation of the afferent bladder signaling in normal and pathological conditions
Global climate forcing of aerosols embodied in international trade
International trade separates regions consuming goods and services from regions where goods and related aerosol pollution are produced. Yet the role of trade in aerosol climate forcing attributed to different regions has never been quantified. Here, we contrast the direct radiative forcing of aerosols related to regions’ consumption of goods and services against the forcing due to emissions produced in each region. Aerosols assessed include black carbon, primary organic aerosol, and secondary inorganic aerosols, including sulfate, nitrate and ammonium. We find that global aerosol radiative forcing due to emissions produced in East Asia is much stronger than the forcing related to goods and services ultimately consumed in that region because of its large net export of emissions-intensive goods. The opposite is true for net importers such as Western Europe and North America: global radiative forcing related to consumption is much greater than the forcing due to emissions produced in these regions. Overall, trade is associated with a shift of radiative forcing from net importing to net exporting regions. Compared to greenhouse gases such as carbon dioxide, the short atmospheric lifetimes of aerosols cause large localized differences between consumption- and production-related radiative forcing. International efforts to reduce emissions in the exporting countries will help alleviate trade-related climate and health impacts of aerosols while lowering global emissions
Reduced expression of lamin A/C correlates with poor histological differentiation and prognosis in primary gastric carcinoma
<p>Abstract</p> <p>Background</p> <p>Lamin A/C is very important in DNA replication, RNA dependent transcription and nuclear stabilization. Reduced or absent lamin A/C expression has been found to be a common feature of a variety of different cancers. To investigate the role of lamin A/C in gastric carcinoma (GC) pathogenesis, we analyzed the correlations between the lamin A/C expression level and clinicopathological factors and studied its prognostic role in primary GC.</p> <p>Methods</p> <p>The expression of lamin A/C at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Lamin A/C expression and its prognostic significance were investigated by performing immunohistochemical analysis on a total of 126 GC clinical tissue samples.</p> <p>Results</p> <p>Both lamin A/C mRNA and protein expression were downregulated in the majority of tumours compared with corresponding normal gastric tissues (<it>p </it>= 0.011 and <it>p </it>= 0.036, respectively). Real time RT-PCR further validated that downregulation of lamin A/C is associated with poor histological differentiation (r = 0.438, <it>p </it>= 0.025). The immunohistochemical staining showed an evident decrease of lamin A/C expression in 55.6% (70/126) GC cases. Importantly, the negative lamin A/C expression correlated strongly with histological classification (r = 0.361, <it>p </it>= 0.034). Survival analysis revealed that patients with lamin A/C downregulation have a poorer prognosis (<it>p </it>= 0.034). In addition, lamin A/C expression was found to be an independent prognostic factor by multivariate analysis.</p> <p>Conclusion</p> <p>Data of this study suggest that lamin A/C is involved in the pathogenesis of GC, and it may serve as a valuable biomarker for assessing the prognosis for primary GC.</p
Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer
To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected. Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P < 0.01). The density of blood vessels in or around the tumor area was 12.27 ± 1.21 and 22.25 ± 2.69 per field in Endostar-treated mice and controls (P < 0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84 ± 0.81 vs. 13.83 ± 1.08, P < 0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer
The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth
Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeleto ns. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology
Recommended from our members
Impact of ENSO longitudinal position on teleconnections to the NAO
While significant improvements have been made in understanding how the El Niño–Southern Oscillation (ENSO) impacts both North American and Asian climate, its relationship with the North Atlantic Oscillation (NAO) remains less clear. Observations indicate that ENSO exhibits a highly complex relationship with the NAO-associated atmospheric circulation. One critical contribution to this ambiguous ENSO/NAO relationship originates from ENSO’s diversity in its spatial structure. In general, both eastern (EP) and central Pacific (CP) El Niño events tend to be accompanied by a negative NAO-like atmospheric response. However, for two different types of La Niña the NAO response is almost opposite. Thus, the NAO responses for the CP ENSO are mostly linear, while nonlinear NAO responses dominate for the EP ENSO. These contrasting extra-tropical atmospheric responses are mainly attributed to nonlinear air-sea interactions in the tropical eastern Pacific. The local atmospheric response to the CP ENSO sea surface temperature (SST) anomalies is highly linear since the air-sea action center is located within the Pacific warm pool, characterized by relatively high climatological SSTs. In contrast, the EP ENSO SST anomalies are located in an area of relatively low climatological SSTs in the eastern equatorial Pacific. Here only sufficiently high positive SST anomalies during EP El Niño events are able to overcome the SST threshold for deep convection, while hardly any anomalous convection is associated with EP La Niña SSTs that are below this threshold. This ENSO/NAO relationship has important implications for NAO seasonal prediction and places a higher requirement on models in reproducing the full diversity of ENSO
The YEATS domain of Taf14 in Saccharomyces cerevisiae has a negative impact on cell growth
The role of a highly conserved YEATS protein motif is explored in the context of the Taf14 protein of Saccharomyces cerevisiae. In S. cerevisiae, Taf14 is a protein physically associated with many critical multisubunit complexes including the general transcription factors TFIID and TFIIF, the chromatin remodeling complexes SWI/SNF, Ino80 and RSC, Mediator and the histone modification enzyme NuA3. Taf14 is a member of the YEATS superfamily, conserved from bacteria to eukaryotes and thought to have a transcription stimulatory activity. However, besides its ubiquitous presence and its links with transcription, little is known about Taf14’s role in the nucleus. We use structure–function and mutational analysis to study the function of Taf14 and its well conserved N-terminal YEATS domain. We show here that the YEATS domain is not necessary for Taf14’s association with these transcription and chromatin remodeling complexes, and that its presence in these complexes is dependent only on its C-terminal domain. Our results also indicate that Taf14’s YEATS domain is not necessary for complementing the synthetic lethality between TAF14 and the general transcription factor TFIIS (encoded by DST1). Furthermore, we present evidence that the YEATS domain of Taf14 has a negative impact on cell growth: its absence enables cells to grow better than wild-type cells under stress conditions, like the microtubule destabilizing drug benomyl. Moreover, cells expressing solely the YEATS domain grow worser than cells expressing any other Taf14 construct tested, including the deletion mutant. Thus, this highly conserved domain should be considered part of a negative regulatory loop in cell growth
- …