Improved spatial separation of neutral molecules

We have developed and experimentally demonstrated an improved electrostatic deflector for the spatial separation of molecules according to their dipole-moment-to-mass ratio. The device features a very open structure that allows for significantly stronger electric fields as well as for stronger deflection without molecules crashing into the device itself. We have demonstrated its performance using the prototypical OCS molecule and we discuss opportunities regarding improved quantum-state-selectivity for complex molecules and the deflection of unpolar molecules.Comment: 6 figure

Evaluation of lung function changes before and after surfactant application during artificial ventilation in newborn rats with congenital diaphragmatic hernia

Patients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research into optimal ventilatory regimen is essential to improve survival rate and to prevent ongoing lung damage. Against this background, the effect of exogenous surfactant application is evaluated. In newborn rats, CDH was induced after a single dose of 2,4 dichloro-4'-nitrophenyl (Nitrofen) (400 mg/kg) on day 10 of gestation. The newborn rats were intubated immediately after hysterotomy, transferred to a heated multichambered body plethysmograph, and artificially ventilated. Inspiratory peak pressures were initially set at 17 cm H2O, with positive end-expiratory pressure at 0 cm H2O and FIO2at 1.0. The pressure was raised in steps of 5 cm H2O, from 5 to 30 cm H2O, to obtain pressure- volume diagrams at 0, 1, and 6 hours of artificial ventilation. These measurements were obtained in controls and in CDH rats with and without endotracheal installation of bovine surfactant (n = 4 to 10 in each group). Significant differences in lung volume between CDH and control rats were observed at all time-points. Surfactant application had a positive effect on lung volume, especially in control rats at t = 1 hour. No significant differences were observed between the CDH groups at t = 1 or t = 6 hours. In this animal model, the effect of artificial ventilation as well as the beneficial short-term effect of exogenous surfactant application have been evaluated. A continued positive effect on lung volume in CDH lungs could not be determined. Routine administration of exogenous surfactant in human CDH patients is not supported by these experimental results

The association between indoor temperature and body mass index in children:the PIAMA birth cohort study

Background: Several experimental studies showed consistent evidence for decreased energy expenditure at higher ambient temperatures. Based on this, an association between thermal exposure and body weight may be expected. However, the effect of thermal exposure on body weight has hardly been studied. Therefore, this study investigated the association between indoor temperature and body mass index (BMI) in children in real life. Methods: This longitudinal observational study included 3 963 children from the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort that started in 1996. These children were followed from birth until the age of 11 years. Winter indoor temperature (living room and bedroom) was reported at baseline and BMI z-scores were available at 10 consecutive ages. Missing data were multiply imputed. Associations between indoor temperature and BMI were analyzed using generalized estimating equations (GEE), adjusted for confounders and stratified by gender. In a subgroup of 104 children, bedroom temperature was also measured with data loggers. Results: Mean reported living room and bedroom temperature were 20.3 degrees C and 17.4 degrees C, respectively. Reported and measured bedroom temperatures were positively correlated (r = 0.42, p = 0.001). Neither reported living room temperature (-0.03 = 0.04) and bedroom temperature (-0.01 = 0.02) nor measured bedroom temperature (-0.04 = 0.05) were associated with BMI z-score between the age of 3 months and 11 years. Conclusions: This study in children did not support the hypothesized association between indoor temperature and BMI in a real life setting

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial

Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia–Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m2) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% 6 3% vs 90% 6 4%; Plog-rank 5 .64), event-free survival (EFS; 87% 6 3% vs 89% 6 4%; Plog-rank 5 .71), and cumulative incidence of relapse/ nonresponse (CIR/NR; 6% 6 3% vs 6% 6 2%; PGray 5 .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% 6 16% vs 88% 6 3%; Plog rank 5 .0008) and gain of chromosome 8 (CIR/NR, 16% 6 7% vs 3% 6 2%, PGray 5 .02; 5-year EFS, 73% 6 8% vs 91% 6 4%, Plog rank 5 .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. (Blood. 2017;129(25): 3314-3321

Detecting and correcting partial errors: Evidence for efficient control without conscious access

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed

Performance breakdown effects dissociate from error detection effects in typing

Mistakes in skilled performance are often observed to be slower than correct actions. This error slowing has been associated with cognitive control processes involved in performance monitoring and error detection. A limited literature on skilled actions, however, suggests that preerror actions may also be slower than accurate actions. This contrasts with findings from unskilled, discrete trial tasks, where preerror performance is usually faster than accurate performance. We tested 3 predictions about error-related behavioural changes in continuous typing performance. We asked participants to type 100 sentences without visual feedback. We found that (a) performance before errors was no different in speed than that before correct key-presses, (b) error and posterror key-presses were slower than matched correct key-presses, and (c) errors were preceded by greater variability in speed than were matched correct key-presses. Our results suggest that errors are preceded by a behavioural signature, which may indicate breakdown of fluid cognition, and that the effects of error detection on performance (error and posterror slowing) can be dissociated from breakdown effects (preerror increase in variability). © 2013 © 2013 The Experimental Psychology Society

Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus

Characterization of two relacidines belonging to a novel class of circular lipopeptides that act against Gram-negative bacterial pathogens

The development of sustainable agriculture and the increasing antibiotic resistance of human pathogens call for novel antimicrobial compounds. Here, we describe the extraction and characterization of a class of cationic circular lipopeptides, for which we propose the name relacidines, from the soil bacterium Brevibacillus laterosporus MG64. Relacidines are composed of a fatty acid side chain (4-methylhexanoic acid) and 13 amino acid residues. A lactone ring is formed by the last five amino acid residues and three positively charged ornithines are located in the linear fragment. Relacidines selectively combat Gram-negative pathogens, including phytopathogens and human pathogens. Further investigation of the mode of action revealed that relacidine B binds to the lipopolysaccharides but does not form pores in the cell membrane. We also provide proof to show that relacidine B does not affect the biosynthesis of the cell wall and RNA. Instead, it affects the oxidative phosphorylation process of cells and diminishes the biosynthesis of ATP. Transcription of relacidines is induced by plant pathogens, which strengthens the potential of B. laterosporus MG64 to be used as a biocontrol agent. Thus, we identified a new group of potent antibiotic compounds for combating Gram-negative pathogens of plants or animals