46 research outputs found
Orbital-Free Molecular Dynamics Simulations of Melting in Na8 and Na20: Melting in Steps
The melting-like transitions of Na8 and Na20 are investigated by ab initio
constant energy molecular dynamics simulations, using a variant of the
Car-Parrinello method which employs an explicit electronic kinetic energy
functional of the density, thus avoiding the use of one-particle orbitals.
Several melting indicators are evaluated in order to determine the nature of
the various transitions, and compared with other simulations. Both Na8 and Na20
melt over a wide temperature range. For Na8, a transition is observed to begin
at approx. 110 K, between a rigid phase and a phase involving isomerizations
between the different permutational isomers of the ground state structure. The
``liquid'' phase is completely established at approx. 220 K. For Na20, two
transitions are observed: the first, at approx. 110 K, is associated with
isomerization transitions between those permutational isomers of the ground
state structure which are obtained by interchanging the positions of the
surface-like atoms; the second, at approx. 160 K, involves a structural
transition from the ground state isomer to a new set of isomers with the
surface molten. The cluster is completely ``liquid'' at approx. 220 K.Comment: Revised version, accepted for publication in J. Chem. Phys. The
changes include longer simulations for the Na20 microcluster, a more complete
comparison to previous theoretical results, and the discussion of some
technical details of the method applie
Collective electronic excitations in metal-coated C_60
ProducciĂłn CientĂficaA two-shell jellium-on-jellium model has been used to study the collective electronic excitations of C_60 coated by an increasing number N of Na atoms. We predict a transition from the Ï-electron polarization of the fullerene to the metallic sodium polarization as a function of increasing N. For low coverages, the Na layer produces only a broadening and fragmentation of the Ï plasmon of C_60. However, if the coverage is large enough, a Na surface plasmon appears. This occurs only after the electron density of the cluster clearly shows two distinct regions, the outer one having an ââaverageââ density similar to that in pure Na metal or Na clusters. The induced density at the collective-mode frequency shows structure corresponding to two interfaces, C_(60-)Na and Na vacuum, the first peak becoming less pronounced as the coverage increases due to a transfer of oscillator strength to the metallic counterpart. The static polarizability per electron also shows this trend and tends slowly to the Na value from below after an initial sharp rise in the region NâŒ13â21
Microscopic dynamics in the liquid Li-Na alloy: An ab initio molecular dynamics study
ProducciĂłn CientĂficaWe present results for several structural and dynamical properties of the liquid Li1-xNax alloy. The study has been carried out by means of the orbital-free ab initio molecular dynamics method, combined with local ionic pseudopotentials constructed within the same framework. We obtain good agreement with the available experimental data, reproducing accurately, the strong homocoordinating tendencies exhibited by this alloy. The calculated partial dynamic structure factors exhibit clear side peaks whose frequencies, for q<~0.25Ă
-1, correspond to the hydrodynamic sound dispersion of the binary alloy, whereas for larger q values fast and slow sound modes are identified. The mass ratio in this system, mNa/mLiâ3, is the smallest one so far for which the fast mode is observed
Collective ionic dynamics in the liquid Na-Cs alloy: An ab initio molecular dynamics study
ProducciĂłn CientĂficaWe present results for several structural and dynamical properties of the liquid Na-Cs alloy. The study has
been carried out by means of the orbital-free ab initio molecular dynamics method, combined with local ionic
pseudopotentials constructed within the same framework. The results show good agreement with the available
experimental data, reproducing the homocoordinating tendency exhibited by this alloy
Orbital free ab initio molecular dynamics study of liquid Al near melting
ProducciĂłn CientĂficaThe orbital free ab initio molecular dynamics method is applied to study the static and dynamic
structure of liquid Al near the triple point. The method uses a new kinetic energy functional, along
with a local pseudopotential constructed within the same kinetic energy functional. The results
obtained for the dynamic structure factor are compared with recent experimental data
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Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.
Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.Funding information:
National Heart, Lung, and Blood Institute,
Grant/Award Numbers: HL 122596, HL124021,
HL124074, HL128297, HL141080, HL155346-01,
R35HL150807, R56HL141206
Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart
Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027.
SuamyaDaswas supported by NIH grants R35HL150807, UH3 TR002878 andAHASFRN35120123. ZhenjiaWangwas supported
by NIH grant (R01EB027078). Pilar MartĂn was supported by MCIN-ISCIII-Fondo de InvestigaciĂłn Sanitaria grant PI22/01759.
KennethW.Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 andUH3CA241694. Tianji
Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH,
NIH-NHLBI grant R56HL141206 and Chicago Biomedical ConsortiumCatalyst Award. EduardoMarbĂĄn was supported byNIH
R01 HL124074 and HL155346-01.S
Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance
At high internal doses, pharmaceuticals have the potential for inducing biological/pharmacological effects in fish. One particular concern for the environment is their potential to bioaccumulate and reach pharmacological levels; the study of these implications for environmental risk assessment has therefore gained increasing attention. To avoid unnecessary testing on animals, in vitro methods for assessment of xenobiotic metabolism could aid in the ecotoxicological evaluation. Here we report the use of a 3-D in vitro liver organoid culture system (spheroids) derived from rainbow trout to measure the metabolism of seven pharmaceuticals using a substrate depletion assay. Of the pharmaceuticals tested, propranolol, diclofenac and phenylbutazone were metabolised by trout liver spheroids; atenolol, metoprolol, diazepam and carbamazepine were not. Substrate depletion kinetics data was used to estimate intrinsic hepatic clearance by this spheroid model, which was similar for diclofenac and approximately 5 fold higher for propranolol when compared to trout liver microsomal fraction (S9) data. These results suggest that liver spheroids could be used as a relevant and metabolically competent in vitro model with which to measure the biotransformation of pharmaceuticals in fish; and propranolol acts as a reproducible positive control
Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management
<p>Abstract</p> <p>Background</p> <p>The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control.</p> <p>Method</p> <p>45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol.</p> <p>Results</p> <p>Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets.</p> <p>Conclusions</p> <p>We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 ÎŒm) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus.</p> <p>Study design</p> <p>Open bench, Observational, Cough, Aerosol study</p
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain âŒ38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio