Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study.

BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects. METHODS: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy. RESULTS: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts. CONCLUSIONS: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.

Electronic screening-enhanced hole pairing in two-leg spin ladders studied by high-resolution resonant inelastic x-ray scattering at Cu M edges.

We study the electronic screening mechanisms of the effective Coulomb on-site repulsion in hole-doped Sr(14)Cu(24)O(41) compared to undoped La(6)Ca(8)Cu(24)O(41) using polarization dependent high-resolution resonant inelastic x-ray scattering at Cu M edges. By measuring the energy of the effective Coulomb on-site repulsion and the spin excitations, we estimate superexchange and hopping matrix element energies along rungs and legs, respectively. Interestingly, hole doping locally screens the Coulomb on-site repulsion reducing it by as much as 25%. We suggest that the increased ratio of the electronic kinetic to the electronic correlation energy contributes to the local superexchange mediated pairing between holes.

Controllable magnetic doping of the surface state of a topological insulator.

A combined experimental and theoretical study of doping individual Fe atoms into Bi(2)Se(3) is presented. It is shown through a scanning tunneling microscopy study that single Fe atoms initially located at hollow sites on top of the surface (adatoms) can be incorporated into subsurface layers by thermally activated diffusion. Angle-resolved photoemission spectroscopy in combination with ab initio calculations suggest that the doping behavior changes from electron donation for the Fe adatom to neutral or electron acceptance for Fe incorporated into substitutional Bi sites. According to first principles calculations within density functional theory, these Fe substitutional impurities retain a large magnetic moment, thus presenting an alternative scheme for magnetically doping the topological surface state. For both types of Fe doping, we see no indication of a gap at the Dirac point.

Beta-1,3-glucanase from Delftia tsuruhatensis strain MV01 and its potential application in vinification.

During vinification microbial activities can spoil wine quality. As the wine-related lactic acid bacterium Pediococcus parvulus is able to produce slimes consisting of a ß-1,3-glucan, must and wine filtration can be difficult or impossible. In addition, the metabolic activities of several wild-type yeasts can also negatively affect wine quality. Therefore, there is a need for measures to degrade the exopolysaccharide from Pediococcus parvulus and to inhibit the growth of certain yeasts. We examined an extracellular ß-1,3-glucanase from Delftia tsuruhatensis strain MV01 with regard to its ability to hydrolyze both polymers, the ß-1,3-glucan from Pediococcus and that from yeast cell walls. The 29-kDa glycolytic enzyme was purified to homogeneity. It exhibited an optimal activity at 50°C and pH 4.0. The sequencing of the N terminus revealed significant similarities to ß-1,3-glucanases from different bacteria. In addition, the investigations indicated that this hydrolytic enzyme is still active under wine-relevant parameters such as elevated ethanol, sulfite, and phenol concentrations as well as at low pH values. Therefore, the characterized enzyme seems to be a useful tool to prevent slime production and undesirable yeast growth during vinification.

Subacute coronary stent thrombosis in a patient developing clopidogrel associated thrombotic thrombocytopenic purpura.

Clopidogrel, in combination with aspirin, is commonly used for the prevention of thrombosis in patients who have received coronary artery stents. As a rare but critical complication, clopidogrel associated thrombotic thrombocytopenic purpura (TTP) has previously been described. A 78 year old man presented with unstable angina and filiform subtotal stenosis of the left anterior descending artery. He was treated with balloon angioplasty and stent implantation. After four days the patient again had angina caused by stent thrombosis, which was treated with balloon angioplasty. During hospital stay the typical course of clopidogrel associated TTP was observed with thrombocytopenia and petechial purpura occurring 14 days after drug initiation and prompt response to therapeutic plasma exchanges. These findings strongly suggest that clopidogrel may have increased platelet activation and aggregation in this immunologically susceptible patient, ultimately leading to a stent thrombosis.