Modeling of metabolism at the genome‐scale has proved to be an efficient method for explaining the phenotypic traits observed in living organisms. Further, it can be used as a means of predicting the ...effect of genetic modifications for example, development of microbial cell factories. With the increasing amount of genome sequencing data available, there exists a need to accurately and efficiently generate such genome‐scale metabolic models (GEMs) of nonmodel organisms, for which data is sparse. In this study, we present an automatic reconstruction approach applied to 24 Penicillium species, which have potential for production of pharmaceutical secondary metabolites or use in the manufacturing of food products, such as cheeses. The models were based on the MetaCyc database and a previously published Penicillium GEM and gave rise to comprehensive genome‐scale metabolic descriptions. The models proved that while central carbon metabolism is highly conserved, secondary metabolic pathways represent the main diversity among species. The automatic reconstruction approach presented in this study can be applied to generate GEMs of other understudied organisms, and the developed GEMs are a useful resource for the study of Penicillium metabolism, for example, for the scope of developing novel cell factories.
Penicillium species are well known to produce antibiotics, like the penicillin, but they can also produce a broader spectrum of metabolites. Here, Prigent and coworkers study the metabolism of 24 Penicillium species and especially the secondary metabolism that is producing a range of complex metabolites. They show that this secondary metabolism is the main force shaping the global metabolism of those species.
The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence ...for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).
In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.
After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval CI, 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).
In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).
Ruminant diets include cereals, protein feeds, their by-products as well as hay and grass, grass/legume, whole-crop maize, small grain or sorghum silages. Furthermore, ruminants are annually or ...seasonally fed with grazed forage in many parts of the World. All these forages could be contaminated by several exometabolites of mycotoxigenic fungi that increase and diversify the risk of mycotoxin exposure in ruminants compared to swine and poultry that have less varied diets. Evidence suggests the greatest exposure for ruminants to some regulated mycotoxins (aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone) and to many other secondary metabolites produced by different species of Alternaria spp. (e.g., AAL toxins, alternariols, tenuazonic acid or 4Z-infectopyrone), Aspergillus flavus (e.g., kojic acid, cyclopiazonic acid or β-nitropropionic acid), Aspergillus fuminatus (e.g., gliotoxin, agroclavine, festuclavines or fumagillin), Penicillium roqueforti and P. paneum (e.g., mycophenolic acid, roquefortines, PR toxin or marcfortines) or Monascus ruber (citrinin and monacolins) could be mainly related to forage contamination. This review includes the knowledge of mycotoxin occurrence reported in the last 15 years, with special emphasis on mycotoxins detected in forages, and animal toxicological issues due to their ingestion. Strategies for preventing the problem of mycotoxin feed contamination under farm conditions are discussed.
This paper presents methods for continuous condition monitoring of railway switches and crossings (S&C, turnout) via sleeper-mounted accelerometers at the crossing transition. The methods are ...developed from concurrently measured sleeper accelerations and scanned crossing geometries from six in situ crossing panels. These measurements combined with a multi-body simulation (MBS) model with a structural track model and implemented scanned crossing geometries are used to derive the link between the crossing geometry condition and the resulting track excitation. From this analysis, a crossing condition indicator Cλ1-λ2, γ is proposed. The indicator is defined as the root mean square (RMS) of a track response signal
that has been band-passed between frequencies corresponding to track deformation wavelength bounds of λ1 and λ2 for the vehicle passing speed (
=
/ λ). In this way, the indicator ignores the quasi-static track response with wavelengths predominantly above λ1 and targets the dynamic track response caused by the kinematic wheel-crossing interaction governed by the crossing geometry. For the studied crossing panels, the indicator C1-0.2 m, γ (λ1=1 and λ2=0.2) was evaluated for
=
,
, or
as in displacements, velocities, and accelerations, respectively. It is shown that this condition indicator has a strong correlation with vertical wheel-rail contact forces that is sustained for various track conditions. Further, model calibrations were performed to measured sleeper displacements for the six investigated crossing panels. The calibrated models show (1) a good agreement between measured and simulated sleeper displacements for the lower frequency quasi-static track response and (2) improved agreement for the dynamic track response at higher frequencies. The calibration also improved the agreement between measurements and simulation for the crossing condition indicator demonstrating the value of model calibration for condition monitoring purposes.
An iterative procedure for numerical prediction of long-term degradation of railway track geometry (longitudinal level) due to accumulated differential settlement of ballast/subgrade is presented. ...The procedure is based on a time-domain model of dynamic vehicle–track interaction to calculate the contact loads between sleepers and ballast in the short-term, which are then used in an empirical model to determine the settlement of ballast/subgrade below each sleeper in the long-term. The number of load cycles (wheel passages) accounted for in each iteration step is determined by an adaptive step length given by a maximum settlement increment. To reduce the computational effort for the simulations of dynamic vehicle–track interaction, complex-valued modal synthesis with a truncated modal set is applied for the linear subset of the discretely supported track model with non-proportional spatial distribution of viscous damping. Gravity loads and state-dependent vehicle, track and wheel–rail contact conditions are accounted for as external loads on the modal model, including situations involving loss of (and recovered) wheel–rail contact, impact between hanging sleeper and ballast, and/or a prescribed variation of non-linear track support stiffness properties along the track model. The procedure is demonstrated by calculating the degradation of longitudinal level over time as initiated by a prescribed initial local rail irregularity (dipped welded rail joint).
Aspergillus niger is perhaps the most important fungus used in biotechnology, and is also one of the most commonly encountered fungi contaminating foods and feedstuffs, and occurring in soil and ...indoor environments. Many of its industrial applications have been given GRAS status (generally regarded as safe). However, A. niger has the potential to produce two groups of potentially carcinogenic mycotoxins: fumonisins and ochratoxins. In this study all available industrial and many non-industrial strains of A. niger (180 strains) as well as 228 strains from 17 related black Aspergillus species were examined for mycotoxin production. None of the related 17 species of black Aspergilli produced fumonisins. Fumonisins (B(2), B(4), and B(6)) were detected in 81% of A. niger, and ochratoxin A in 17%, while 10% of the strains produced both mycotoxins. Among the industrial strains the same ratios were 83%, 33% and 26% respectively. Some of the most frequently used strains in industry NRRL 337, 3112 and 3122 produced both toxins and several strains used for citric acid production were among the best producers of fumonisins in pure agar culture. Most strains used for other biotechnological processes also produced fumonisins. Strains optimized through random mutagenesis usually maintained their mycotoxin production capability. Toxigenic strains were also able to produce the toxins on media suggested for citric acid production with most of the toxins found in the biomass, thereby questioning the use of the remaining biomass as animal feed. In conclusion it is recommended to use strains of A. niger with inactive or inactivated gene clusters for fumonisins and ochratoxins, or to choose isolates for biotechnological uses in related non-toxigenic species such as A. tubingensis, A. brasiliensis, A vadensis or A. acidus, which neither produce fumonisins nor ochratoxins.
Out-of-roundness in railway wheels, in particular polygonal wear resulting in regular, multi-lobed, out-of-round wheels, has become a significant problem in recent years. It is of concern to railway ...operators due to the increased noise and vibration it can cause. This polygonisation is caused by cyclic wear but the exact mechanism leading to this type of wear is not fully understood. It appears to be the result of dynamic linking between a resonance or other periodic excitation in the coupled vehicle-track system and the existing wear at the wheel. This paper reviews the developing body of research being carried out in many countries by research groups, manufacturers and operators. Some examples of polygonisation on different types of railway vehicles are reported including feight trains, urban transit trains and high-speed trains. The main theories for the formation mechanisms are presented and the current measurement methods, computer simulation techniques and the effects and potential mitigation methods are reviewed. In parallel, the mechanisms and consequences of discrete wheel tread irregularities, such as wheel flats and material fall-out due to rolling contact fatigue cracking, are addressed.
The computer program DIFF, which is being developed at CHARMEC since the late 1980s, is used to simulate vertical vehicle–track interaction at high frequencies, from about 20
Hz to at least 2000
Hz. ...Measured results from two field test campaigns are used to validate the vehicle–track interaction model. The first test case involves impact loads from a wheel flat, while the other case studies the influence of a corrugated rail on dynamic vertical wheel–rail contact forces. Four vehicle models and two visco-elastic track models are compared. The track models are calibrated versus test data from laboratory and field tests. Input data on rail and wheel roughness are taken from field measurements. Good agreement between calculated and measured vertical contact forces is observed, both with respect to magnitude and frequency content, for most frequencies below 2000
Hz. The best agreement is obtained when using a vehicle model that accounts for both wheelsets in a bogie, instead of using a single wheelset model.
Background Device-detected subclinical atrial fibrillation (AF) refers to infrequent, short-lasting, asymptomatic AF that is detected only with long-term continuous monitoring. Subclinical AF is ...common and associated with an increased risk of stroke; however, the risk of stroke with subclinical AF is lower than for clinical AF, and very few patients with subclinical AF alone have been included in large AF anticoagulation trials. The net benefit of anticoagulation in patients with subclinical AF is unknown. Design ARTESiA is a prospective, multicenter, double-blind, randomized controlled trial, recruiting patients with subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor, and who have additional risk factors for stroke. Patients with clinical AF documented by surface electrocardiogram will be excluded from the study. Participants will be randomized to receive either apixaban (according to standard AF dosing) or aspirin 81 mg daily. The primary outcome is the composite of stroke, transient ischemic attack with diffusion-weighted magnetic resonance imaging evidence of cerebral infarction, and systemic embolism. Approximately 4,000 patients will be enrolled from around 230 clinical sites, with an anticipated mean follow-up of 36 months until 248 adjudicated primary outcome events have occurred. Summary ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with subclinical AF and additional risk factors.
To compare left ventricular function after a long-term His or para-His pacing (HP) and right ventricular septal pacing (RVSP) in patients with atrioventricular block (AVB).
We included consecutive ...patients with AVB, a narrow QRS < 120 ms, and a preserved left ventricular ejection fraction (LVEF) >0.40, in a prospective, randomized, double-blinded, crossover design. All patients were treated with 12 months HP and 12 months RVSP. A total of 38 patients mean age, 67 ± 10 years; 30 (79%) men were included. The primary endpoint was LVEF, which was significantly lower after a 12 months RVSP (0.50 ± 0.11) than after 12 months of HP (0.55 ± 0.10), P = 0.005. We measured the difference in time-to-peak systolic velocity between opposite basal segments in the apical views by using tissue Doppler imaging. In the four-chamber view, the difference was 58 (±7) ms after RVSP and 49 (±7) ms after HP, P = 0.27; in the two-chamber view, the difference was 45 (±5) ms after RVSP and 31 ±(4) ms after HP, P = 0.02, and in the apical long-axis view, the difference was 63 (±6) after RVSP and 44 (±7) after HP, P = 0.03. There was no difference in New York Heart Association class, 6-min hall walk test, quality-of-life assessments, or device-related complications. The mean threshold was significantly higher in HP leads than in RVSP leads.
His or para-His pacing preserves LVEF and mechanical synchrony as compared with RVSP after 12 months pacing in patients with AVB, narrow QRS, and LVEF > 0.40.
PDF
