helicase fails to complement loss of Prp43p in .

Helicase proteins have important roles in many aspects of RNA metabolism in the cell. The function of these highly conserved proteins is commonly preserved between organisms, yet in a few cases these homologues are found to have slightly different biochemical functions. Prp43 is a protein with varied roles in yeast, but here we show that the homologue of this protein is unable to rescue the loss of Prp43p.

Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies.

Older patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of adverse events (AEs) due to decreased protective organ function and increased comorbidities. TONADO® 1 + 2 were replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials comparing the efficacy and safety of tiotropium/olodaterol (5/5 µg) versus the monocomponents via the Respimat® inhaler in patients with moderate-to-very-severe COPD. In this prespecified safety analysis, patients were grouped by age.

Prospects for continuous-wave molecular modulation in Raman-active microresonators.

We propose the extension of existing molecular modulation techniques for continuous-wave optical modulation to Raman-active microresonators. Intense pump and Stokes modes inside a microresonator prepare a high coherence of the Raman transition between two ro-vibrational states. With the coherence prepared, any laser in the optical region can be coupled to the microresonator and be modulated.

Phase-dependent ionization of hydrogen by intense sub-cycle pulses: publisher's note.

This publisher's note corrects an error in Eq. (2) in Opt. Lett.

Phase-dependent ionization of hydrogen by intense sub-cycle pulses.

We have performed simulations and analytic calculations that show strong carrier-envelope phase dependence in the ionization of hydrogen atoms using intense sub-cycle sub-femtosecond laser pulses. When the pulse width is comparable to the classical orbit time of the initial bound state, sine-like pulses can ionize more than cosine-like pulses that have the same fluence. This result is the opposite of what is expected from a tunneling-like model, where the ionization probability primarily depends on the peak amplitude of the electric field during the pulse.

Continuous-wave modulation of a femtosecond oscillator using coherent molecules.

We describe a new method to broaden the frequency spectrum of a femtosecond oscillator in the continuous-wave (CW) domain. The method relies on modulating the femtosecond laser using four-wave mixing inside a Raman-based optical modulator. We prepare the modulator by placing deuterium molecules inside a high-finesse cavity and driving their fundamental vibrational transition using intense pump and Stokes lasers that are locked to the cavity modes.

Effect of tiotropium and olodaterol on symptoms and patient-reported outcomes in patients with COPD: results from four randomised, double-blind studies.

Unlabelled: Chronic obstructive pulmonary disease is associated with significant morbidity and mortality. Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations, while patients are much more concerned about symptoms and health status. Our aim was to investigate the effects of tiotropium + olodaterol on patient-reported health outcomes, breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease, compared to placebo, tiotropium or olodaterol monotherapy.

Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO and OTEMTO studies: a subgroup analysis by age.

Background: Increasing age is associated with poor prognosis in patients with COPD.

Objective: This analysis from the replicate Phase III OTEMTO and TONADO studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years.

Methods: In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.

Implicating SCF complexes in organogenesis in Caenorhabditis elegans.

Development of the Caenorhabditis elegans foregut (pharynx) is regulated by a network of proteins that includes the Retinoblastoma protein (pRb) ortholog LIN-35; the ubiquitin pathway components UBC-18 and ARI-1; and PHA-1, a cytoplasmic protein. Loss of pha-1 activity impairs pharyngeal development and body morphogenesis, leading to embryonic arrest. We have used a genetic suppressor approach to dissect this complex pathway.

Pooled subpopulation analyses of the effects of roflumilast on exacerbations and lung function in COPD.

Background: This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting β2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outcomes.

Methods: Data were pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily roflumilast 500 μg in patients with COPD. Endpoints were mean rate of exacerbations and change from baseline in pre- and postbronchodilator FEV1.

Safety and efficacy of the once-daily anticholinergic BEA2180 compared with tiotropium in patients with COPD.

Background: To determine the safety and efficacy of BEA2180, an anticholinergic agent in patients with chronic obstructive pulmonary disease (COPD).

Methods: Smokers or ex-smokers ≥40 years with COPD and a postbronchodilator forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≤70% participated in this multinational, randomised, double-blind, parallel study. Patients received BEA2180 (50, 100 or 200 μg), tiotropium (5 μg) or placebo once daily via Respimat Soft Mist™.

Profile of ciclesonide for the maintenance treatment of asthma.

Ciclesonide is a nonhalogenated synthetic inhaled corticosteroid (ICS) that has been approved by the US Food and Drug Administration for the treatment of all severities of persistent asthma. It is available as a hydrofluroalkane pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160 mcg/activation, with the recommenced dosage being two inhalations twice-daily. It is a prodrug that is converted in the lung to its active form, which possesses 100-fold greater glucocorticoid-receptor-binding affinity than the parent compound.

Effectiveness of omalizumab in reducing corticosteroid burden in patients with moderate to severe persistent allergic asthma.

Background: Asthma guidelines advocate maintaining asthma control while minimizing corticosteroid exposure.

Objective: To assess the reduction in corticosteroid burden during long-term treatment and the corresponding impact of this reduction on asthma control, lung function, and inflammation in patients with moderate to severe allergic asthma.

Methods: We conducted a pooled analysis (N = 1,071) of 2 similarly designed, randomized, double-blind, placebo-controlled omalizumab trials and their extension phases.

Genetics of yeast impacting wine quality.

The availability of the sequence of the Saccharomyces genome in combination with the development of chemical analytical technologies with dynamic ranges sensitive enough to detect volatile aromatic compounds has generated a renewed interest in defining the role of yeast in the generation of wine aroma and flavor. Genetic differences among wine strains are well documented and aroma profiles also appear to vary, implying that specific allelic alterations may exist and impact the production of compounds associated with flavor. Partial or complete sequencing data on several wine strains are available and reveal underlying genetic differences across strains in key genes implicated in flavor formation.

Differences in physicians' self-reported knowledge of, attitudes toward, and responses to the black box warning on long-acting beta-agonists.

Background: Inhaled corticosteroids and long-acting beta-agonists (LABAs) are recommended for treating moderate to severe persistent asthma. The Food and Drug Administration has issued a black box warning (BBW) for LABAs.

Objective: To investigate physician knowledge of the BBW and its effect on the practice of specialists (pulmonologists and allergists) and primary care physicians (PCPs) (internists and family physicians).

One-year treatment with mometasone furoate in chronic obstructive pulmonary disease.

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo.

Inhaled mometasone furoate improves health-related quality of life in patients with persistent asthma.

Results from two clinical trials of mometasone furoate administered via a dry powder inhaler (MF-DPI) were reviewed to evaluate the consistency of effects of MF-DPI administered once-daily in the evening (QD PM) or twice-daily (BID) on health-related quality of life (HRQOL) in adults with persistent asthma previously treated with inhaled corticosteroids. HRQOL data were collected from two 12-week, randomized, double-blind trials: in study 1 (n = 268), patients received MF-DPI 400 microg QD PM (1 inhalation), MF-DPI 200 microg BID, or placebo; in study 2 (n = 400), patients received MF-DPI 200 microg QD PM, MF-DPI 400 microg QD PM (1 inhalation), MF-DPI 200 microg BID, MF-DPI 400 microg QD PM (2 inhalations of 200 microg), or placebo. In both studies, HRQOL was assessed using the Medical Outcomes Survey 36-item Short Form (SF-36) and an asthma-specific module.

Bronchodilator efficacy of the fixed combination of ipratropium and albuterol compared to albuterol alone in moderate-to-severe persistent asthma.

Background: The potential of anticholinergics to provide bronchodilatory benefits over short-acting beta(2)-agonists (SABA) alone in patients with moderate-to-severe persistent asthma has not been well defined.

Methods: An outpatient, randomized, double-blind, single-dose, crossover study in adult asthmatics with moderate-to-severe obstruction despite treatment with inhaled corticosteroids (ICS) was conducted comparing the fixed combination of ipratropium and albuterol (IB+ALB) to albuterol alone (ALB). Serial spirometry was performed over 6h.

Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma.

Background: Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma.

Scope: Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms 'mometasone furoate AND pharmacology' and 'mometasone furoate AND asthma AND clinical trial'. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed.

Functional genomics of wine yeast Saccharomyces cerevisiae.

The application of genomic technologies to the analysis of wine strains of Saccharomyces cerevisiae has greatly enhanced our understanding of both native and laboratory strains of this important model eukaryote. Not only are differences in transcript, protein, and metabolite profiles being uncovered, but the heritable basis of these differences is also being elucidated. Although some challenges remain in the application of functional genomic technologies to commercial and native strains of S.

The appropriate omalizumab patient.

Allergy is a significant component in many asthma patients. Omalizumab is a monoclonal anti-immunoglobulin E antibody for the treatment of allergic asthma. Clinical trials have shown that omalizumab treatment is associated with improved symptom control and reduced inhaled corticosteroid doses, resulting in fewer exacerbations and reduced utilization of resources.

Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma.

Objective: The reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma.

Methods: A 3-month, double-blind, placebo-controlled clinical trial (n=123), followed by a 9-month open-label phase (n=120). The study was conducted at 26 medical centers in the United States.

Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma.

Study Objectives: Oral corticosteroids (OCS) may be associated with systemic adverse events (AEs), which can be reduced by replacing OCS with inhaled corticosteroids (ICS). The potential of ciclesonide, a novel ICS, to reduce OCS use in patients with severe, persistent asthma was evaluated in this study.

Design: A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study.

Aquaporins in Saccharomyces cerevisiae wine yeast.

AQY1 and AQY2 were sequenced from five commercial and five native wine yeasts. Of these, two AQY1 alleles from UCD 522 and UCD 932 were identified that encoded three or four amino-acid changes, respectively, compared with the Sigma1278b sequence. Oocytes expressing these AQY1 alleles individually exhibited increased water permeability vs.

Effects of mometasone furoate given once daily in the evening on lung function and symptom control in persistent asthma.

Background: The chronobiology of asthma suggests that, for once-daily dosing, an evening dose may be the most effective treatment paradigm.

Objective: To evaluate the efficacy and safety of mometasone furoate dry powder inhaler (MF-DPI) administered once daily in the evening or twice daily in patients with asthma previously maintained on twice-daily regimens of inhaled corticosteroids.

Methods: In this 12-week, multicenter, placebo-controlled trial, 268 subjects > or =12 years of age with inhaled corticosteroid-dependent asthma and baseline forced expiratory volume in 1 second (FEV(1)) between 50% and 85% of predicted were randomized to receive treatment with MF-DPI 400 mug once daily in the evening, MF-DPI 200 mug twice daily, or placebo.