536 research outputs found
Predicting crystal structures: the Parrinello-Rahman method revisited
By suitably adapting a recent approach [A. Laio and M. Parrinello, PNAS, 99,
12562 (2002)] we develop a powerful molecular dynamics method for the study of
pressure-induced structural transformations. We use the edges of the simulation
cell as collective variables. In the space of these variables we define a
metadynamics that drives the system away from the local minimum towards a new
crystal structure. In contrast to the Parrinello-Rahman method our approach
shows no hysteresis and crystal structure transformations can occur at the
equilibrium pressure. We illustrate the power of the method by studying the
pressure-induced diamond to simple hexagonal phase transition in a model of
silicon.Comment: 5 pages, 2 Postscript figures, submitte
Design of a low band gap oxide ferroelectric: BiTiO
A strategy for obtaining low band gap oxide ferroelectrics based on charge
imbalance is described and illustrated by first principles studies of the
hypothetical compound BiTiO, which is an alternate stacking of
the ferroelectric BiTiO. We find that this compound is
ferroelectric, similar to BiTiO although with a reduced
polarization. Importantly, calculations of the electronic structure with the
recently developed functional of Tran and Blaha yield a much reduced band gap
of 1.83 eV for this material compared to BiTiO. Therefore,
BiTiO is predicted to be a low band gap ferroelectric material
Glycolipid self-assembly: micellar structure
Small-angle scattering is used to investigate a typical glycolipid micelle structure in conjunction with NMR determination of sugar cycle conformation. It is shown that the ellipsoidal shape of the micelle originates from two constraints: sugar rings perpendicular to the interface induce a limited area at the chain-head interface. Together with the bulky hydrated heads, this imposes an ellipsoidal shape
Super-telomeres in transformed human fibroblasts
Telomere length maintenance is critical for organisms' long-term survival and cancer cell proliferation. Telomeres are kept within species-specific length ranges by the interplay between telomerase activity and telomeric chromatin organization. In this paper, we exploited telomerase immortalized human fibroblasts (cen3tel) that gradually underwent neoplastic transformation during culture propagation to study telomere composition and length regulation during the transformation process. Just after telomerase catalytic subunit (hTERT) expression, cen3tel telomeres shortened despite the presence of telomerase activity. At a later stage and concomitantly with transformation, cells started elongating telomeres, which reached a mean length greater than 100kb in about 900 population doublings. Super-telomeres were stable and compatible with cell growth and tumorigenesis. Telomere extension was associated with increasing levels of telomerase activity that were linked to the deregulation of endogenous telomerase RNA (hTERC) and exogenous telomerase reverse transcriptase (hTERT) expression. Notably, the increase in hTERC levels paralleled the increase in telomerase activity, suggesting that this subunit plays a role in regulating enzyme activity. Telomeres ranging in length between 10 and more than 100kb were maintained in an extendible state although TRF1 and TRF2 binding increased with telomere length. Super-telomeres neither influenced subtelomeric region global methylation nor the expression of the subtelomeric gene FRG1, attesting the lack of a clear-cut relationship between telomere length, subtelomeric DNA methylation and expression in human cells. The cellular levels of the telomeric proteins hTERT, TRF1, TRF2 and Hsp90 rose with transformation and were independent of telomere length, pointing to a role of these proteins in tumorigenesis
Charging Induced Emission of Neutral Atoms from NaCl Nanocube Corners
Detachment of neutral cations/anions from solid alkali halides can in
principle be provoked by donating/subtracting electrons to the surface of
alkali halide crystals, but generally constitutes a very endothermic process.
However, the amount of energy required for emission is smaller for atoms
located in less favorable positions, such as surface steps and kinks. For a
corner ion in an alkali halide cube the binding is the weakest, so it should be
easier to remove that atom, once it is neutralized. We carried out first
principles density functional calculations and simulations of neutral and
charged NaCl nanocubes, to establish the energetics of extraction of
neutralized corner ions. Following hole donation (electron removal) we find
that detachment of neutral Cl corner atoms will require a limited energy of
about 0.8 eV. Conversely, following the donation of an excess electron to the
cube, a neutral Na atom is extractable from the corner at the lower cost of
about 0.6 eV. Since the cube electron affinity level (close to that a NaCl(100)
surface state, which we also determine) is estimated to lie about 1.8 eV below
vacuum, the overall energy balance upon donation to the nanocube of a zero
energy electron from vacuum will be exothermic. The atomic and electronic
structure of the NaCl(100) surface, and of the nanocube Na and Cl corner
vacancies are obtained and analyzed as a byproduct.Comment: 16 pages, 2 table, 7 figure
Effect of divalent and monovalent cations on calf thymus PCNA-independent DNA polymerase δ and its 3' → 5' exonuclease
AbstractRecent data suggest that DNA polymerases α and δ might have a coordinate functional role at the replication fork. In this communication we show that Mg2+ is likely the natural metal activator for both enzymes. Mn2+, a known mutagenic agent, is a competitive inhibitor of Mg2+ for DNA polymerase δ and acompetitive for DNA polymerase α. The 3'→ 5' exonuclease activity associated with DNA polymerase δ is not affected upon addition of Mn2+, Be2+, another mutagenic agent, on the other hand, has an inhibitory effect on the 3' → 5' exonuclease, but not on the DNA polymerase δ. The data presented might explain the mutagenic and carcinogenic potential of these two divalent cations
Metric tensor as the dynamical variable for variable cell-shape molecular dynamics
We propose a new variable cell-shape molecular dynamics algorithm where the
dynamical variables associated with the cell are the six independent dot
products between the vectors defining the cell instead of the nine cartesian
components of those vectors. Our choice of the metric tensor as the dynamical
variable automatically eliminates the cell orientation from the dynamics.
Furthermore, choosing for the cell kinetic energy a simple scalar that is
quadratic in the time derivatives of the metric tensor, makes the dynamics
invariant with respect to the choice of the simulation cell edges. Choosing the
densitary character of that scalar allows us to have a dynamics that obeys the
virial theorem. We derive the equations of motion for the two conditions of
constant external pressure and constant thermodynamic tension. We also show
that using the metric as variable is convenient for structural optimization
under those two conditions. We use simulations for Ar with Lennard-Jones
parameters and for Si with forces and stresses calculated from first-principles
of density functional theory to illustrate the applications of the method.Comment: 10 pages + 6 figures, Latex, to be published in Physical Review
Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral activity.
Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonu-cleotides to deoxyribonucleotides, we have now prepared and evaluated 5′-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 μM for the UDP analogue 5′-deoxy-5′- N-(phosphon-acetyl)uridine sodium salt (amide) to 600 μM for the CDP analogue 5′- O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100–500 μM concentrations, whereas ADP analogue 5′- N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5′-deoxy-5′- N-(phos-phon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 μM) against HSV-2 and a modest inhibitory activity (EC50: 110 μM) against HIV-1, respectively
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