Stability of Colloidal Quasicrystals

Freezing of charge-stabilized colloidal suspensions and relative stabilities of crystals and quasicrystals are studied using thermodynamic perturbation theory. Macroion interactions are modelled by effective pair potentials combining electrostatic repulsion with polymer-depletion or van der Waals attraction. Comparing free energies -- counterion terms included -- for elementary crystals and rational approximants to icosahedral quasicrystals, parameters are identified for which one-component quasicrystals are stabilized by a compromise between packing entropy and cohesive energy.Comment: 6 pages, 4 figure

Effective Interactions and Volume Energies in Charge-Stabilized Colloidal Suspensions

Charge-stabilized colloidal suspensions can be conveniently described by formally reducing the macroion-microion mixture to an equivalent one-component system of pseudo-particles. Within this scheme, the utility of a linear response approximation for deriving effective interparticle interactions has been demonstrated [M. J. Grimson and M. Silbert, Mol. Phys. 74, 397 (1991)]. Here the response approach is extended to suspensions of finite-sized macroions and used to derive explicit expressions for (1) an effective electrostatic pair interaction between pseudo-macroions and (2) an associated volume energy that contributes to the total free energy. The derivation recovers precisely the form of the DLVO screened-Coulomb effective pair interaction for spherical macroions and makes manifest the important influence of the volume energy on thermodynamic properties of deionized suspensions. Excluded volume corrections are implicitly incorporated through a natural modification of the inverse screening length. By including nonlinear response of counterions to macroions, the theory may be generalized to systematically investigate effective many-body interactions.Comment: 13 pages (J. Phys.: Condensed Matter, in press

Effective Interactions and Volume Energies in Charged Colloids: Linear Response Theory

Interparticle interactions in charge-stabilized colloidal suspensions, of arbitrary salt concentration, are described at the level of effective interactions in an equivalent one-component system. Integrating out from the partition function the degrees of freedom of all microions, and assuming linear response to the macroion charges, general expressions are obtained for both an effective electrostatic pair interaction and an associated microion volume energy. For macroions with hard-sphere cores, the effective interaction is of the DLVO screened-Coulomb form, but with a modified screening constant that incorporates excluded volume effects. The volume energy -- a natural consequence of the one-component reduction -- contributes to the total free energy and can significantly influence thermodynamic properties in the limit of low-salt concentration. As illustrations, the osmotic pressure and bulk modulus are computed and compared with recent experimental measurements for deionized suspensions. For macroions of sufficient charge and concentration, it is shown that the counterions can act to soften or destabilize colloidal crystals.Comment: 14 pages, including 3 figure

Kinomic Profiling of Electromagnetic Navigational Bronchoscopy Specimens: A New Approach for Personalized Medicine

Purpose Researchers are currently seeking relevant lung cancer biomarkers in order to make informed decisions regarding therapeutic selection for patients in so-called “precision medicine.” However, there are challenges to obtaining adequate lung cancer tissue for molecular analyses. Furthermore, current molecular testing of tumors at the genomic or transcriptomic level are very indirect measures of biological response to a drug, particularly for small molecule inhibitors that target kinases. Kinase activity profiling is therefore theorized to be more reflective of in vivo biology than many current molecular analysis techniques. As a result, this study seeks to prove the feasibility of combining a novel minimally invasive biopsy technique that expands the number of lesions amenable for biopsy with subsequent ex vivo kinase activity analysis. Methods Eight patients with lung lesions of varying location and size were biopsied using the novel electromagnetic navigational bronchoscopy (ENB) technique. Basal kinase activity (kinomic) profiles and ex vivo interrogation of samples in combination with tyrosine kinase inhibitors erlotinib, crizotinib, and lapatinib were performed by PamStation 12 microarray analysis. Results Kinomic profiling qualitatively identified patient specific kinase activity profiles as well as patient and drug specific changes in kinase activity profiles following exposure to inhibitor. Thus, the study has verified the feasibility of ENB as a method for obtaining tissue in adequate quantities for kinomic analysis and has demonstrated the possible use of this tissue acquisition and analysis technique as a method for future study of lung cancer biomarkers. Conclusions We demonstrate the feasibility of using ENB-derived biopsies to perform kinase activity assessment in lung cancer patients

Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.

Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Influence of solvent granularity on the effective interaction between charged colloidal suspensions

We study the effect of solvent granularity on the effective force between two charged colloidal particles by computer simulations of the primitive model of strongly asymmetric electrolytes with an explicitly added hard sphere solvent. Apart from molecular oscillating forces for nearly touching colloids which arise from solvent and counterion layering, the counterions are attracted towards the colloidal surfaces by solvent depletion providing a simple statistical description of hydration. This, in turn, has an important influence on the effective forces for larger distances which are considerably reduced as compared to the prediction based on the primitive model. When these forces are repulsive, the long-distance behaviour can be described by an effective Yukawa pair potential with a solvent-renormalized charge. As a function of colloidal volume fraction and added salt concentration, this solvent-renormalized charge behaves qualitatively similar to that obtained via the Poisson-Boltzmann cell model but there are quantitative differences. For divalent counterions and nano-sized colloids, on the other hand, the hydration may lead to overscreened colloids with mutual attraction while the primitive model yields repulsive forces. All these new effects can be accounted for through a solvent-averaged primitive model (SPM) which is obtained from the full model by integrating out the solvent degrees of freedom. The SPM was used to access larger colloidal particles without simulating the solvent explicitly.Comment: 14 pages, 16 craphic

Scleroderma and related disorders: 223. Long Term Outcome in a Contemporary Systemic Sclerosis Cohort

Background: We have previously compared outcome in two groups of systemic sclerosis (SSc) patients with disease onset a decade apart and we reported data on 5 year survival and cumulative incidence of organ disease in a contemporary SSc cohort. The present study examines longer term outcome in an additional cohort of SSc followed for 10 years. Methods: We have examined patients with disease onset between years 1995 and 1999 allowing for at least 10 years of follow-up in a group that has characteristics representative for the patients we see in contemporary clinical practice. Results: Of the 398 patients included in the study, 252 (63.3%) had limited cutaneous (lc) SSc and 146 (36.7%) had diffuse cutaneous (dc) SSc. The proportion of male patients was higher among the dcSSc group (17.1% v 9.9%, p = 0.037) while the mean age of onset was significantly higher among lcSSc patients (50 ± 13 v 46 ± 13 years ± SD, p = 0.003). During a 10 year follow-up from disease onset, 45% of the dcSSc and 21% of the lcSSc subjects developed clinically significant pulmonary fibrosis, p < 0.001. Among them approximately half reached the endpoint within the first 3 years (23% of dcSSc and 10% of lcSSc) and over three quarters within the first 5 years (34% and 16% respectively). There was a similar incidence of pulmonary hypertension (PH) in the two subsets with a steady rate of increase over time. At 10 years 13% of dcSSc and 15% of lcSSc subjects had developed PH (p=0.558), with the earliest cases observed within the first 2 years of disease. Comparison between subjects who developed PH in the first and second 5 years from disease onset demonstrated no difference in demographic or clinical characteristics, but 5-year survival from PH onset was better among those who developed this complication later in their disease (49% v 24%), with a strong trend towards statistical significance (p = 0.058). Incidence of SSc renal crisis (SRC) was significantly higher among the dcSSc patients (12% v 4% in lcSSc, p = 0.002). As previously observed, the rate of development of SRC was highest in the first 3 years of disease- 10% in dcSSc and 3% in lcSSc. All incidences of clinically important cardiac disease developed in the first 5 years from disease onset (7% in dcSSc v 1% in lcSSc, p < 0.001) and remained unchanged at 10 years. As expected, 10-year survival among lcSSc subjects was significantly higher (81%) compared to that of dcSSc patients (70%, p = 0.006). Interestingly, although over the first 5 years the death rate was much higher in the dcSSc cohort (16% v 6% in lcSSc), over the following years it became very similar for both subsets (14% and 13% between years 5 and 10, and 18% and 17% between years 10 and 15 for dcSSc and lcSSc respectively). Conclusions: Even though dcSSc patients have higher incidence for most organ complications compared to lcSSc subjects, the worse survival among them is mainly due to higher early mortality rate. Mortality rate after first 5 years of disease becomes comparable in the two disease subsets. Disclosure statement: The authors have declared no conflicts of interes

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10&lt;sup&gt;−8&lt;/sup&gt;, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10&lt;sup&gt;−7&lt;/sup&gt;, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10&lt;sup&gt;−20&lt;/sup&gt;, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10&lt;sup&gt;−22&lt;/sup&gt;, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10&lt;sup&gt;−4&lt;/sup&gt;), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific