Are the energy and virial routes to thermodynamics equivalent for hard spheres?

The internal energy of hard spheres (HS) is the same as that of an ideal gas, so that the energy route to thermodynamics becomes useless. This problem can be avoided by taking an interaction potential that reduces to the HS one in certain limits. In this paper the square-shoulder (SS) potential characterized by a hard-core diameter $\sigma'$, a soft-core diameter $\sigma>\sigma'$ and a shoulder height $\epsilon$ is considered. The SS potential becomes the HS one if (i) $\epsilon\to 0$, or (ii) $\epsilon\to\infty$, or (iii) $\sigma'\to\sigma$ or (iv) $\sigma'\to 0$ and $\epsilon\to\infty$. The energy-route equation of state for the HS fluid is obtained in terms of the radial distribution function for the SS fluid by taking the limits (i) and (ii). This equation of state is shown to exhibit, in general, an artificial dependence on the diameter ratio $\sigma'/\sigma$. If furthermore the limit $\sigma'/\sigma\to 1$ is taken, the resulting equation of state for HS coincides with that obtained through the virial route. The necessary and sufficient condition to get thermodynamic consistency between both routes for arbitrary $\sigma'/\sigma$ is derived.Comment: 10 pages, 4 figures; v2: minor changes; to be published in the special issue of Molecular Physics dedicated to the Seventh Liblice Conference on the Statistical Mechanics of Liquids (Lednice, Czech Republic, June 11-16, 2006

Phase diagram of the penetrable square well-model

We study a system formed by soft colloidal spheres attracting each other via a square-well potential, using extensive Monte Carlo simulations of various nature. The softness is implemented through a reduction of the infinite part of the repulsive potential to a finite one. For sufficiently low values of the penetrability parameter we find the system to be Ruelle stable with square-well like behavior. For high values of the penetrability the system is thermodynamically unstable and collapses into an isolated blob formed by a few clusters each containing many overlapping particles. For intermediate values of the penetrability the system has a rich phase diagram with a partial lack of thermodynamic consistency.Comment: 6 pages and 5 figure

Lane-formation vs. cluster-formation in two dimensional square-shoulder systems: A genetic algorithm approach

Introducing genetic algorithms as a reliable and efficient tool to find ordered equilibrium structures, we predict minimum energy configurations of the square shoulder system for different values of corona width $\lambda$. Varying systematically the pressure for different values of $\lambda$ we obtain complete sequences of minimum energy configurations which provide a deeper understanding of the system's strategies to arrange particles in an energetically optimized fashion, leading to the competing self-assembly scenarios of cluster-formation vs. lane-formation.Comment: 5 pages, 6 figure

Generation of defects and disorder from deeply quenching a liquid to form a solid

We show how deeply quenching a liquid to temperatures where it is linearly unstable and the crystal is the equilibrium phase often produces crystalline structures with defects and disorder. As the solid phase advances into the liquid phase, the modulations in the density distribution created behind the advancing solidification front do not necessarily have a wavelength that is the same as the equilibrium crystal lattice spacing. This is because in a deep enough quench the front propagation is governed by linear processes, but the crystal lattice spacing is determined by nonlinear terms. The wavelength mismatch can result in significant disorder behind the front that may or may not persist in the latter stage dynamics. We support these observations by presenting results from dynamical density functional theory calculations for simple one- and two-component two-dimensional systems of soft core particles.Comment: 25 pages, 11 figure

Why do ultrasoft repulsive particles cluster and crystallize? Analytical results from density functional theory

We demonstrate the accuracy of the hypernetted chain closure and of the mean-field approximation for the calculation of the fluid-state properties of systems interacting by means of bounded and positive-definite pair potentials with oscillating Fourier transforms. Subsequently, we prove the validity of a bilinear, random-phase density functional for arbitrary inhomogeneous phases of the same systems. On the basis of this functional, we calculate analytically the freezing parameters of the latter. We demonstrate explicitly that the stable crystals feature a lattice constant that is independent of density and whose value is dictated by the position of the negative minimum of the Fourier transform of the pair potential. This property is equivalent with the existence of clusters, whose population scales proportionally to the density. We establish that regardless of the form of the interaction potential and of the location on the freezing line, all cluster crystals have a universal Lindemann ratio L = 0.189 at freezing. We further make an explicit link between the aforementioned density functional and the harmonic theory of crystals. This allows us to establish an equivalence between the emergence of clusters and the existence of negative Fourier components of the interaction potential. Finally, we make a connection between the class of models at hand and the system of infinite-dimensional hard spheres, when the limits of interaction steepness and space dimension are both taken to infinity in a particularly described fashion.Comment: 19 pages, 5 figures, submitted to J. Chem. Phys; new version: minor changes in structure of pape

Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.

The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed

Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma

Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.National Institutes of Health (U.S.) (U54 CA210180)MIT/Mayo Physical Sciences Center for Drug Distribution and Drug Efficacy in Brain TumorsDana-Farber Cancer Institute (PLGA Fund)Lundbeck FoundationNovo Nordisk Foundatio

The sub-seasonal to seasonal prediction (S2S) project database

A database containing sub-seasonal to seasonal forecasts from 11 operational centres is available to the research community and will help advance our understanding of the sub-seasonal to seasonal time range. Demands are growing rapidly in the operational prediction and applications communities for forecasts that fill the gap between medium-range weather and long-range or seasonal forecasts. Based on the potential for improved forecast skill at the sub-seasonal to seasonal time range, a sub-seasonal prediction (S2S) research project has been established by the World Weather Research Program/World Climate Research Program. A main deliverable of this project is the establishment of an extensive database, containing sub-seasonal (up to 60 days) forecasts, 3-weeks behind real-time, and reforecasts from 11 operational centers, modelled in part on the THORPEX Interactive Grand Global Ensemble (TIGGE) database for medium range forecasts (up to 15 days). The S2S database, available to the research community since May 2015, represents an important tool to advance our understanding of the sub-seasonal to seasonal time range that has been considered for a long time as a “desert of predictability”. In particular, this database will help identify common successes and shortcomings in the model simulation and prediction of sources of sub-seasonal to seasonal predictability. For instance, a preliminary study suggests that the S2S models underestimate significantly the amplitude of the Madden Julian Oscillation (MJO) teleconnections over the Euro-Atlantic sector. The S2S database represents also an important tool for case studies of extreme events. For instance, a multi-model combination of S2S models displays higher probability of a landfall over Vanuatu islands 2 to 3 weeks before tropical cyclone Pam devastated the islands in March 2015

Stress-Induced Activation of Heterochromatic Transcription

Constitutive heterochromatin comprising the centromeric and telomeric parts of chromosomes includes DNA marked by high levels of methylation associated with histones modified by repressive marks. These epigenetic modifications silence transcription and ensure stable inheritance of this inert state. Although environmental cues can alter epigenetic marks and lead to modulation of the transcription of genes located in euchromatic parts of the chromosomes, there is no evidence that external stimuli can globally destabilize silencing of constitutive heterochromatin. We have found that heterochromatin-associated silencing in Arabidopsis plants subjected to a particular temperature regime is released in a genome-wide manner. This occurs without alteration of repressive epigenetic modifications and does not involve common epigenetic mechanisms. Such induced release of silencing is mostly transient, and rapid restoration of the silent state occurs without the involvement of factors known to be required for silencing initiation. Thus, our results reveal new regulatory aspects of transcriptional repression in constitutive heterochromatin and open up possibilities to identify the molecular mechanisms involved