163 research outputs found
Crowding effect on helix-coil transition: beyond entropic stabilization
We report circular dichroism measurements on the helix-coil transition of
poly(L-glutamic acid) in solution with polyethylene glycol (PEG) as a crowding
agent. Using small angle neutron scattering, PEG solutions have been
characterized and found to be well described by the picture of a transient
network of mesh size , usual for semi-diluted chains in good solvent. We
show that the increase of PEG concentration stabilizes the helices and
increases the transition temperature. But more unexpectedly we also notice that
the increase of crowding agent concentration reduces the mean helix extent at
the transition, or in other words reduces its cooperative feature. This result
cannot be accounted for by an entropic stabilization mechanism. Comparing the
mean length of helices at the transition and the mesh size of the PEG network,
our results strongly suggest two regimes: helices shorter or longer than the
mesh size
Pacman percolation: a model for enzyme gel degradation
We study a model for the gel degradation by an enzyme, where the gel is
schematized as a cubic lattice, and the enzyme as a random walker, that cuts
the bonds over which it passes. The model undergoes a (reverse) percolation
transition, which for low density of enzymes falls in a universality class
different from random percolation. In particular we have measured a gel
fraction critical exponent beta=1.0+-0.1, in excellent agreement with
experiments made on the real system.Comment: 4 pages, 7 eps figure
Bending elasticity of a curved amphiphilic film decorated anchored copolymers: a small angle neutron scattering study
Microemulsion droplets (oil in water stabilized by a surfactant film) are
progressively decorated with increasing amounts of poly ethylene- oxide (PEO)
chains anchored in the film by the short aliphatic chain grafted at one end of
the PEO chain . The evolution of the bending elasticity of the surfactant film
with increasing decoration is deduced from the evolution in size and
polydispersity of the droplets as reflected by small angle neutron scattering.
The optimum curvature radius decreases while the bending rigidity modulus
remains practically constant. The experimental results compare well with the
predictions of a model developed for the bending properties of a curved film
decorated by non-adsorbing polymer chains, which takes into account, the finite
curvature of the film and the free diffusion of the chains on the film.Comment: 30 June 200
Small Angle Scattering and Zeta Potential of Liposomes Loaded with Octa(carboranyl)porphyrazine
In this work the physicochemical characterization of liposomes loaded with a
newly synthesised carboranyl porphyrazine (H2HECASPz) is described. This
molecule represents a potential drug for different anticancer therapies, such
as Boron Neutron Capture Therapy, Photodynamic Therapy and Photothermal
Therapy. Different loading methods and different lipid mixtures were tested.
The corresponding loaded vectors were studied by Small Angle Scattering (SANS
and SAXS), light scattering and zeta potential. The combined analysis of
structural data at various length scales and the measurement of the surface
charge allowed to obtain a detailed characterization of the investigated
systems. The mechanisms underlying the onset of differences in relevant
physicochemical parameters (size, polydispersity and charge) were also
critically discussed
Robust Phase Behavior of Model Transient networks
In order to study the viscoelastic properties of certain complex fluids which
are described in terms of a multiconnected transient network we have developed
a convenient model system composed of microemulsion droplets linked by
telechelic polymers. The phase behavior of such systems has two characteristic
features: a large monophasic region which consists of two sub-regions (a fluid
sol phase and a viscoelastic gel phase) separated by a percolation line and a
two phase region at low volume fraction with separation into a dilute sol phase
and a concentrated gel phase. From the plausible origin of these features we
expect them to be very similar in different systems. We describe here the phase
behavior of four different systems we prepared in order to vary the time scale
of the dynamical response of the transient network; they consist of the
combination of two oil(decane) in water microemulsions differing by the
stabilizing surfactant monolayer (Cetyl pyridinium chloride/octanol or
TX100/TX35) and of two telechelic polymers which are end-grafted poly (ethylene
oxide) chains, differing by the end-grafted hydrophobic aliphatic chains
(C12H25 or C18H37).Comment: April 9 200
Blood Signature of Pre-Heart Failure: A Microarrays Study
International audienceBACKGROUND: The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: 294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification. CONCLUSIONS/SIGNIFICANCE: These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF
Happy heart syndrome. role of positive emotional stress in takotsubo syndrome
AIMS: Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term 'broken heart syndrome'. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS.
METHODS AND RESULTS: Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with 'happy heart syndrome' was similar to those with the 'broken heart syndrome' including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in 'happy hearts' compared with 'broken hearts' (35.0 vs. 16.3%, P = 0.030).
CONCLUSION: Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the 'happy hearts' than among the 'broken hearts'. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS
A novel clinical score (InterTAK Diagnostic Score) to differentiate takotsubo syndrome from acute coronary syndrome: results from the International Takotsubo Registry
AIMS. Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage.
METHODS AND RESULTS: Patients with TTS were recruited from the International Takotsubo Registry ( www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96-0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of â„50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score â€31 were diagnosed as ACS, âŒ95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87-0.93).
CONCLUSION: The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity
Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial
Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry
Aims: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). Methods and results: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50\u20133.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78\u20131.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. Conclusion: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621
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