An independent, general method for checking consistency between diffraction data and partial radial distribution functions derived from them: the example of liquid water

There are various routes for deriving partial radial distribution functions of disordered systems from experimental diffraction (and/or EXAFS) data. Due to limitations and errors of experimental data, as well as to imperfections of the evaluation procedures, it is of primary importance to confirm that the end result (partial radial distribution functions) and the primary information (diffraction data) are consistent with each other. We introduce a simple approach, based on Reverse Monte Carlo modelling, that is capable of assessing this dilemma. As a demonstration, we use the most frequently cited set of "experimental" partial radial distribution functions on liquid water and investigate whether the 3 partials (O-O, O-H and H-H) are consistent with the total structure factor of pure liquid D_2O from neutron diffraction and that of H_2O from X-ray diffraction. We find that while neutron diffraction on heavy water is in full agreement with all the 3 partials, the addition of X-ray diffraction data clearly shows problems with the O-O partial radial distribution function. We suggest that the approach introduced here may also be used to establish whether partial radial distribution functions obtained from statistical theories of the liquid state are consistent with the measured structure factors.Comment: 6 pages, 3 figure

Advanced operator-splitting-based semi-implicit spectral method to solve the binary phase-field crystal equations with variable coefficients

We present an efficient method to solve numerically the equations of dissipative dynamics of the binary phase-field crystal model proposed by Elder et al. [Phys. Rev. B 75, 064107 (2007)] characterized by variable coefficients. Using the operator splitting method, the problem has been decomposed into sub-problems that can be solved more efficiently. A combination of non-trivial splitting with spectral semi-implicit solution leads to sets of algebraic equations of diagonal matrix form. Extensive testing of the method has been carried out to find the optimum balance among errors associated with time integration, spatial discretization, and splitting. We show that our method speeds up the computations by orders of magnitude relative to the conventional explicit finite difference scheme, while the costs of the pointwise implicit solution per timestep remains low. Also we show that due to its numerical dissipation, finite differencing can not compete with spectral differencing in terms of accuracy. In addition, we demonstrate that our method can efficiently be parallelized for distributed memory systems, where an excellent scalability with the number of CPUs is observed

Comparison of the TIP4P-2005, SWM4-DP and BK3 interaction potentials of liquid water with respect to their consistency with neutron and X-ray diffraction data of pure water

Following a fairly comprehensive study on popular interaction potentials of water (Pusztai et al 2008, J. Chem. Phys., 129, 184103), here two more recent, polarizable potential sets, SWM4-DP (Lamoureux et al., Chem. Phys. Lett., 2006, 418, 245) and BK3 (Kiss et al. J. Chem. Phys., 2013, 138, 204507) are compared to the TIP4P-2005 water potential (Abascal et al., J. Chem. Phys., 2005, 123, 234505) that had appeared the most favoravble previously. The basis of comparison was the compatibility with results of neutron and X-ray diffraction experiments on pure water, using the scheme applied by Pusztai et al. (2008). The scheme combines the experimental total scattering structure factors (TSSF) and partial radial distribution functions (PRDF) from molecular dynamics simulations in a single structural model. Goodness-of-fit values to the O-O, O-H and H-H simulated PRDF-s and to the experimental neutron and X-ray TSSF provided a measure that can characterize the level of consistency between interaction potentials and diffraction experiments. Among the sets of partial RDF-s investigated here, the ones corresponding to the SWM4-DP potential parameters have proven to be the most consistent with the particular diffraction results taken for the present study, by a hardly significant margin ahead of BK3. Perhaps more importantly, it is shown that the three sets of potential parameters produce nearly equivalent PRDF-s that may all be made consistent with diffraction data at a very high level. The largest differences can be detected in terms of the O-O partial radial distribution function.Слiдуючи досить повному вивченню популярних потенцiалiв взаємодiї для води (Pusztai et al., J. Chem. Phys., 2008, 129, 184103), у цiй роботi два бiльш сучасних потенцiали з врахуванням поляризованостi молекул типу SWM4-DP (Lamoureux et al., Chem. Phys. Lett., 2006, 418, 245) i BK3 (Kiss et al., J. Chem. Phys., 2013, 138, 204507) порiвняно з моделлю TIP4P-2005 (Abascal et al., J. Chem. Phys., 2005, 123, 234505), яка донедавна вважалася найуспiшнiшою. Основою для порiвняння є узгодження з результатами експериментiв по розсiянню нейтронiв та рентгенiвського випромiнювання для чистої води, використовуючи процедуру, розроблену Пустаї та iн. (2008). Ця процедера поєднує повнi структурнi фактори розсiяння i парцiальнi радiальнi функцiї розподiлу, що слiдують з молекулярної динамiки певної структурної моделi. Якiсть узгодження значень функцiй розподiлу O–O, O–H i H–H з моделювання пiсля їх перетворення до повних структурних факторiв i порiвняння з експериментальними факторами є мiрою для опису рiвня узгодження. Серед парцiальних функцiй розподiлу, дослiджених у цiй роботi, тi фактори, якi вiдповiдають моделi SWM4-DP виявилися найкращими, але лише незначно кращими вiд тих, що були отриманi з моделi BK3. Важливо вiдзначити, що усi три потенцiали дають майже еквiвалентнi радiальнi функцiї розподiлу, якi узгоджуються з експериментом, але невелика розбiжнiсть спостерiгається для функцiй розподiлу киснiв O–O

Phase-field approach to polycrystalline solidification including heterogeneous and homogeneous nucleation

Advanced phase-field techniques have been applied to address various aspects of polycrystalline solidification including different modes of crystal nucleation. The height of the nucleation barrier has been determined by solving the appropriate Euler-Lagrange equations. The examples shown include the comparison of various models of homogeneous crystal nucleation with atomistic simulations for the single component hard-sphere fluid. Extending previous work for pure systems (Gránásy L, Pusztai T, Saylor D and Warren J A 2007 Phys. Rev. Lett. 98 art no 035703), heterogeneous nucleation in unary and binary systems is described via introducing boundary conditions that realize the desired contact angle. A quaternion representation of crystallographic orientation of the individual particles (outlined in Pusztai T, Bortel G and Gránásy L 2005 Europhys. Lett. 71 131) has been applied for modeling a broad variety of polycrystalline structures including crystal sheaves, spherulites and those built of crystals with dendritic, cubic, rhombododecahedral, truncated octahedral growth morphologies. Finally, we present illustrative results for dendritic polycrystalline solidification obtained using an atomistic phase-field model

CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer

Introduction We performed gene expression analysis to identify molecular predictors of resistance to preoperative concomitant trastuzumab and paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (T/FEC). Methods Pretreatment fine-needle aspiration specimens from 45 patients with HER-2-overexpressing stage II to IIIA breast cancer were subjected to transcriptional profiling and examined for differential expression of various genes and gene sets. The primary endpoint for tumor response was pathologic complete response (pCR). Correlations between pCR and gene expression were sought. Results The overall pCR rate was 64%. Age, nuclear grade, tumor size, nodal status, quantitative expression of estrogen and HER-2 receptor mRNA, and HER-2 gene copy number showed no correlation with pCR. Results of gene set enrichment analysis suggested that the lower expression of genes involved with CD40 signaling is associated with a greater risk of residual cancer after the preoperative chemotherapy that includes trastuzumab. Conclusion CD40 signaling may play a role in determining response to trastuzumab-plus-T/FEC therapy in patients with HER-2-overexpressing breast cancer.PubMedWoSScopu

Far-infrared vibrational properties of linear C60 polymers: A comparison between neutral and charged materials

We report the far-infrared transmittance spectrum of a pure phase of the orthorhombic high-temperature and high-pressure C-60 polymer and compare the results with a previously published spectrum of the charged RbC60 orthorhombic polymer. Assignments for both spectra are made with the aid of first-principles quantum molecular dynamics simulations of the two materials. We find that the striking spectral differences between the neutral and charged linear fullerene polymers can be fully accounted for by charge effects on the C-60 ball

Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells

Taxanes remain first line chemotherapy in management of metastatic breast cancer and have a key role in epithelial ovarian cancer, with increasingly common use of weekly paclitaxel dosing regimens. However, their clinical utility is limited by the development of chemoresistance. To address this, we modelled in vitro paclitaxel resistance in MCF-7 cells. We show that at clinically relevant drug doses, emerging paclitaxel resistance is associated with profound changes in cell death responses and a switch from apoptosis to autophagy as the principal mechanism of drug-induced cytotoxicity. This was characterised by a complete absence of caspase-mediated apoptotic cell death (using the pan-caspase-inhibitor Z-VAD) in paclitaxel-resistant MCF-7TaxR cells, compared with parent MCF-7 or MDA-MB-231 cell lines on paclitaxel challenge, downregulation of caspase-7, caspase-9 and BCl2-interacting mediator of cell death (BIM) expression. Silencing with small interfering RNA to BIM in MCF-7 parental cells was sufficient to confer paclitaxel resistance, inferring the significance in downregulation of this protein in contributing to the resistant phenotype of the MCF-7TaxR cell line. Conversely, there was an increased autophagic response in the MCF-7TaxR cell line with reduced phospho-mTOR and relative resistance to the mTOR inhibitors rapamycin and RAD001. In conclusion, we show for the first time that paclitaxel resistance is associated with profound changes in cell death response with deletion of multiple apoptotic factors balanced by upregulation of the autophagic pathway and collateral sensitivity to platinum

Functional proteomics can define prognosis and predict pathologic complete response in patients with breast cancer

<p>Abstract</p> <p>Purpose</p> <p>To determine whether functional proteomics improves breast cancer classification and prognostication and can predict pathological complete response (pCR) in patients receiving neoadjuvant taxane and anthracycline-taxane-based systemic therapy (NST).</p> <p>Methods</p> <p>Reverse phase protein array (RPPA) using 146 antibodies to proteins relevant to breast cancer was applied to three independent tumor sets. Supervised clustering to identify subgroups and prognosis in surgical excision specimens from a training set (n = 712) was validated on a test set (n = 168) in two cohorts of patients with primary breast cancer. A score was constructed using ordinal logistic regression to quantify the probability of recurrence in the training set and tested in the test set. The score was then evaluated on 132 FNA biopsies of patients treated with NST to determine ability to predict pCR.</p> <p>Results</p> <p>Six breast cancer subgroups were identified by a 10-protein biomarker panel in the 712 tumor training set. They were associated with different recurrence-free survival (RFS) (log-rank p = 8.8 E-10). The structure and ability of the six subgroups to predict RFS was confirmed in the test set (log-rank p = 0.0013). A prognosis score constructed using the 10 proteins in the training set was associated with RFS in both training and test sets (p = 3.2E-13, for test set). There was a significant association between the prognostic score and likelihood of pCR to NST in the FNA set (p = 0.0021).</p> <p>Conclusion</p> <p>We developed a 10-protein biomarker panel that classifies breast cancer into prognostic groups that may have potential utility in the management of patients who receive anthracycline-taxane-based NST.</p