A 19-channel d.c. SQUID magnetometer system for brain research

A 19-channel d.c. SQUID magnetometer system for neuromagnetic investigations is under constuction. The first-order gradiometers for sensing the signal are placed in a hexagonal configuration. D.c. SQUIDs based on niobium/aluminium technology have been developed, leading to a field sensitivity of about 5 fT/ Hz. SQUID read-out is realized with a resonant transformer circuit at 100 kHz. The multichannel control and detection electronics are compactly built

Electronic relaxation of 1B3u(nπ*) pyrazine in a supersonic jet:Rotational state dependence of the nonradiative rate leading to biexponential decay

The decay of single rotational levels of the vibrationless first excited singlet state of pyrazine (1,4‐diazabenzene) following expansion in a helium supersonic jet and excitation with a pulse dye laser is biexponential, as it is for single vibronic level excitation in the bulk gas phase. However, both the relative contribution and the lifetime of the fast, ’’nonradiative’’, component are strongly dependent on the initial rotational state. A fit to the data shows that the rate of nonradiative decay is proportional to K2, where K is the projection of the rotational angular momentum vector on the (near‐symmetric) top axis. Both the interpretation of these results and their implications with respect to the theory of radiationless transitions are discussed briefly.(AIP

LOFAR early-time search for coherent radio emission from GRB 180706A

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society.The nature of the central engines of gamma-ray bursts (GRBs) and the composition of their relativistic jets are still under debate. If the jets are Poynting flux dominated rather than baryon dominated, a coherent radio flare from magnetic re-connection events might be expected with the prompt gamma-ray emission. There are two competing models for the central engines of GRBs; a black hole or a newly formed milli-second magnetar. If the central engine is a magnetar it is predicted to produce coherent radio emission as persistent or flaring activity. In this paper, we present the deepest limits to date for this emission following LOFAR rapid response observations of GRB 180706A. No emission is detected to a 3$\sigma$ limit of 1.7 mJy beam$^{-1}$ at 144 MHz in a two-hour LOFAR observation starting 4.5 minutes after the gamma-ray trigger. A forced source extraction at the position of GRB 180706A provides a marginally positive (1 sigma) peak flux density of $1.1 \pm 0.9$ mJy. The data were time-sliced into different sets of snapshot durations to search for FRB like emission. No short duration emission was detected at the location of the GRB. We compare these results to theoretical models and discuss the implications of a non-detection.Peer reviewedFinal Accepted Versio

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint—echocardiographic reduction of left ventricular end-systolic volume (LVESV)—were evaluated. Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT

Pharmacological aspects of neonatal antidepressant withdrawal

Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary

Extended RDF: Computability and Complexity Issues

ERDF stable model semantics is a recently proposed semantics for ERDF ontologies and a faithful extension of RDFS semantics on RDF graphs. In this paper, we elaborate on the computability and complexity issues of the ERDF stable model semantics. Based on the undecidability result of ERDF stable model semantics, decidability under this semantics cannot be achieved, unless ERDF ontologies of restricted syntax are considered. Therefore, we propose a slightly modified semantics for ERDF ontologies, called ERDF #n- stable model semantics. We show that entailment under this semantics is, in general, decidable and also extends RDFS entailment. Equivalence statements between the two semantics are provided. Additionally, we provide algorithms that compute the ERDF #n-stable models of syntax-restricted and general ERDF ontologies. Further, we provide complexity results for the ERDF #nstable model semantics on syntax-restricted and general ERDF ontologies. Finally, we provide complexity results for the ERDF stable model semantics on syntax-restricted ERDF ontologies

Bariatric surgery improves postprandial VLDL kinetics and restores insulin mediated regulation of hepatic VLDL production

Dyslipidemia in obesity results from excessive production and impaired clearance of triglyceride-rich (TG-rich) lipoproteins, which are particularly pronounced in the postprandial state. Here, we investigated the impact of Roux-en-Y gastric bypass (RYGB) surgery on postprandial VLDL1 and VLDL2 apoB and TG kinetics and their relationship with insulin-responsiveness indices. Morbidly obese patients without diabetes who were scheduled for RYGB surgery (n = 24) underwent a lipoprotein kinetics study during a mixed-meal test and a hyperinsulinemic-euglycemic clamp study before the surgery and 1 year later. A physiologically based computational model was developed to investigate the impact of RYGB surgery and plasma insulin on postprandial VLDL kinetics. After the surgery, VLDL1 apoB and TG production rates were significantly decreased, whereas VLDL2 apoB and TG production rates remained unchanged. The TG catabolic rate was increased in both VLDL1 and VLDL2 fractions, but only the VLDL2 apoB catabolic rate tended to increase. Furthermore, postsurgery VLDL1 apoB and TG production rates, but not those of VLDL2, were positively correlated with insulin resistance. Insulin-mediated stimulation of peripheral lipoprotein lipolysis was also improved after the surgery. In summary, RYGB resulted in reduced hepatic VLDL1 production that correlated with reduced insulin resistance, elevated VLDL2 clearance, and improved insulin sensitivity in lipoprotein lipolysis pathways.</p

Template-assisted crystallization behavior in stirred solutions of the monoclonal antibody Anti-CD20: probability distributions of induction times

We present a method to determine the template crystallization behavior of proteins. This method is a statistical approach that accounts for the stochastic nature of nucleation. It makes use of batch-wise experiments under stirring conditions in volumes smaller than 0.3 mL to save material while mimicking larger-scale processes. To validate our method, it was applied to the crystallization of a monoclonal antibody of pharmaceutical interest, Anti-CD20. First, we determined the Anti-CD20 phase diagram in a PEG-400/Na2SO4/water system using the batch method, as, to date, no such data on Anti-CD20 solubility have been reported. Then, the probability distribution of induction times was determined experimentally, in the presence of various mesoporous silica template particles, and crystallization of Anti-CD20 in the absence of templates was compared to template-assisted crystallization. The probability distribution of induction times is shown to be a suitable method to determine the effect of template particles on protein crystallization. The induction time distribution allows for the determination of two key parameters of nucleation, the nucleation rate and the growth time. This study shows that the use of silica particles leads to faster crystallization and a higher nucleation rate. The template particle characteristics are shown to be critical parameters to efficiently promote protein crystallization