Study of Foaming Properties and Effect of the Isomeric Distribution of Some Anionic Surfactants

Using different reaction conditions of photosulfochlorination of n-dodecane, two samples of anionic surfactants of sulfonate type are obtained. Their micellar behavior has been already reported and the relationship between their isomeric distribution and their chemical structures and micellar behaviors have been more thoroughly explored. In this investigation, we screened the foaming properties (foaming power and foam stability) by a standardized method very similar to the Ross–Miles foaming tests to identify which surfactants are suitable for applications requiring high foaming, or, alternatively, low foaming. The results obtained for the synthesized surfactants are compared to those obtained for an industrial sample of secondary alkanesulfonate (Hostapur 60) and to those of a commercial sample of sodium dodecylsulfate used as reference for anionic surfactants. The foam formation and foam stability of aqueous solutions of the two samples of dodecanesulfonate are compared as a function of their isomeric distribution. These compounds show good foaming power characterized in most cases by metastable or dry foams. The highest foaming power is obtained for the sample rich in primary isomers which also produces foam with a relatively high stability. For the sample rich in secondary isomers we observe under fixed conditions a comparable initial foam height but the foam stability turns out to be low. This property is interesting for applications requiring low foaming properties such as dishwashing liquid for machines. The best results are observed near and above the critical micellar concentrations and at 25 C for both the samples

The consistency condition for the three-point function in dissipative single-clock inflation

We generalize the consistency condition for the three-point function in single field inflation to the case of dissipative, multi-field, single-clock models. We use the recently introduced extension of the effective field theory of inflation that accounts for dissipative effects, to provide an explicit proof to leading (non-trivial) order in the generalized slow roll parameters and mixing with gravity scales. Our results illustrate the conditions necessary for the validity of the consistency relation in situations with many degrees of freedom relevant during inflation, namely that there is a preferred clock. Departures from this condition in forthcoming experiments would rule out not only single field but also a large class of multi-field models.Comment: 26+11 page

Effects and Detectability of Quasi-Single Field Inflation in the Large-Scale Structure and Cosmic Microwave Background

Quasi-single field inflation predicts a peculiar momentum dependence in the squeezed limit of the primordial bispectrum which smoothly interpolates between the local and equilateral models. This dependence is directly related to the mass of the isocurvatons in the theory which is determined by the supersymmetry. Therefore, in the event of detection of a non-zero primordial bispectrum, additional constraints on the parameter controlling the momentum-dependence in the squeezed limit becomes an important question. We explore the effects of these non-Gaussian initial conditions on large-scale structure and the cosmic microwave background, with particular attention to the galaxy power spectrum at large scales and scale-dependence corrections to galaxy bias. We determine the simultaneous constraints on the two parameters describing the QSF bispectrum that we can expect from upcoming large-scale structure and cosmic microwave background observations. We find that for relatively large values of the non-Gaussian amplitude parameters, but still well within current uncertainties, galaxy power spectrum measurements will be able to distinguish the QSF scenario from the predictions of the local model. A CMB likelihood analysis, as well as Fisher matrix analysis, shows that there is also a range of parameter values for which Planck data may be able distinguish between QSF models and the related local and equilateral shapes. Given the different observational weightings of the CMB and LSS results, degeneracies can be significantly reduced in a joint analysis.Comment: 27 pages, 14 figure

Anomalous Dimensions and Non-Gaussianity

We analyze the signatures of inflationary models that are coupled to strongly interacting field theories, a basic class of multifield models also motivated by their role in providing dynamically small scales. Near the squeezed limit of the bispectrum, we find a simple scaling behavior determined by operator dimensions, which are constrained by the appropriate unitarity bounds. Specifically, we analyze two simple and calculable classes of examples: conformal field theories (CFTs), and large-N CFTs deformed by relevant time-dependent double-trace operators. Together these two classes of examples exhibit a wide range of scalings and shapes of the bispectrum, including nearly equilateral, orthogonal and local non-Gaussianity in different regimes. Along the way, we compare and contrast the shape and amplitude with previous results on weakly coupled fields coupled to inflation. This signature provides a precision test for strongly coupled sectors coupled to inflation via irrelevant operators suppressed by a high mass scale up to 1000 times the inflationary Hubble scale.Comment: 40 pages, 10 figure

S.8.1 An immunochip-based interrogation of scleroderma susceptibility variants

Introduction. Understanding the genetic architecture of scleroderma (SSc) susceptibility is vital both in gene discovery and in determining the influence of previously identified susceptibility variants. It is particularly important in understanding disease mechanism in a disease with few therapies and great morbidity and mortality. Methods. We selected 557 cases from the Australian Scleroderma Cohort Study (ASCS), for genotyping with the Immunochip, a custom Illumina Infinium genotyping array containing 196 524 rare and common variants shown to be important in a wide variety of autoimmune disorders. A total of 4537 controls were taken from the 1958 British Birth cohort. Genotype data were analysed with PLINK. Samples and SNPs with low call rates were excluded, as were SNPs in Hardy-Weinberg disequilibrium or with less than two occurrences of the minor allele. Eigenstrat was used to analyse population structure. The final data set consisted of 505 cases, 4491 controls and 146 867 SNPs. Allelic association analyses were conducted using Fisher's exact test. Genotype clusters were manually examined for all associations of P < 10−5 since calling is difficult for some rare variants. Results. Significant and suggestive associations were detected at seven loci. Several of these have been previously implicated in scleroderma susceptibility (HLA-DRB1 and STAT4) and several are novel associations, including SNPs near PXK (P = 4.4 × 10−6) and CFDP1(P = 2.6 × 10−6). The strongest associations were with SNPs in the Class II region of the MHC. One of the most strongly associated SNPs [rs4639334; P = 1.6 × 10−8; odds ratio (OR) = 1.8] is in linkage disequilibrium (r2 = 0.46) with the Class II allele HLA-DRB1*11:01. This allele has been associated with SSc. Another strongly associated SNP is rs2857130 (P = 1.6 × 10−8; OR = 0.67), which lies in the promoter region of HLA-DRB1, but is not in LD with any classical MHC alleles. Outside the MHC, there were six regions of association with P < 10−5,including the confirmed SSc locus at STAT4. Several SNPs implicate a locus at PXK, which has been previously associated with SLE but not with SSc. The remaining associations are novel for both SSc and SLE and require replication. Of particular interest is a rare variant located within a non-coding RNA on chromosome 6q21 which was ∼20 times more frequent in cases than controls. We are currently dissecting the potential biological implications of this locus. Conclusions. This pilot study has confirmed previously reported SSc associations, revealed further genetic overlap between SSc and SLE, and identified putative novel SSc susceptibility loci including a rare allele with major effect siz

S.11.1 Influence of digital ulcer healing on disability and daily activity limitations in SSc

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of D

Numerical evaluation of the bispectrum in multiple field inflation

We present a complete framework for numerical calculation of the power spectrum and bispectrum in canonical inflation with an arbitrary number of light or heavy fields. Our method includes all relevant effects at tree-level in the loop expansion, including (i) interference between growing and decaying modes near horizon exit; (ii) correlation and coupling between species near horizon exit and on superhorizon scales; (iii) contributions from mass terms; and (iv) all contributions from coupling to gravity. We track the evolution of each correlation function from the vacuum state through horizon exit and the superhorizon regime, with no need to match quantum and classical parts of the calculation; when integrated, our approach corresponds exactly with the tree-level Schwinger or 'in-in' formulation of quantum field theory. In this paper we give the equations necessary to evolve all two- and three-point correlation functions together with suitable initial conditions. The final formalism is suitable to compute the amplitude, shape, and scale dependence of the bispectrum in models with |fNL| of order unity or less, which are a target for future galaxy surveys such as Euclid, DESI and LSST. As an illustration we apply our framework to a number of examples, obtaining quantitatively accurate predictions for their bispectra for the first time. Two accompanying reports describe publicly-available software packages that implement the method

The Antifibrotic Effect of A2B Adenosine Receptor Antagonism in a Mouse Model of Dermal Fibrosis

Objective: Systemic sclerosis (SSc; scleroderma) is a chronic disease that affects the skin and various internal organs. Dermal fibrosis is a major component of this disease. The mechanisms that promote dermal fibrosis remain elusive. Elevations in tissue adenosine levels and the subsequent engagement of the profibrotic A2B adenosine receptor (ADORA2B) have been shown to regulate fibrosis in multiple organs including the lung, kidney, and penis; however, the role of ADORA2B in dermal fibrosis has not been investigated. We undertook this study to test our hypothesis that elevated expression of ADORA2B in the skin drives the development of dermal fibrosis. Methods: We assessed the involvement of ADORA2B in the regulation of dermal fibrosis using a well-established mouse model of dermal fibrosis. Using an orally active ADORA2B antagonist, we demonstrated how inhibition of ADORA2B results in reduced dermal fibrosis in 2 distinct experimental models. Finally, using human dermal fibroblasts, we characterized the expression of adenosine receptors. Results: We demonstrated that levels of ADORA2B were significantly elevated in dermal fibrosis and that the therapeutic blockade of this receptor in vivo using an ADORA2B antagonist could reduce the production of profibrotic mediators in the skin and attenuate dermal fibrosis. Antagonism of ADORA2B resulted in reduced numbers of arginase-expressing macrophages and myofibroblasts and in reduced levels of the extracellular matrix proteins fibronectin, collagen, and hyaluronan. Conclusion: These findings identify ADORA2B as a potential profibrotic regulator in dermal fibrosis and suggest that ADORA2B antagonism may be a useful approach for the treatment of SSc

A randomised, parallel-group, double-blind, placebo-controlled phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis: DAISY study design and rationale

OBJECTIVES: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY). METHODS: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints). CONCLUSIONS: The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc