Deceleration and Trapping of SrF Molecules.

We report on the electrostatic trapping of neutral SrF molecules. The molecules are captured from a cryogenic buffer-gas beam source into the moving traps of a 4.5-m-long traveling-wave Stark decelerator. The SrF molecules in X^{2}Σ^{+}(v=0,N=1) state are brought to rest as the velocity of the moving traps is gradually reduced from 190 m/s to zero. The molecules are held for up to 50 ms in multiple electric traps of the decelerator. The trapped packets have a volume (FWHM) of 1 mm^{3} and a velocity spread of 5(1) m/s, which corresponds to a temperature of 60(20) mK. Our result demonstrates a factor 3 increase in the molecular mass that has been Stark decelerated and trapped. Heavy molecules (mass>100 amu) offer a highly increased sensitivity to probe physics beyond the standard model. This work significantly extends the species of neutral molecules of which slow beams can be created for collision studies, precision measurement, and trapping experiments.

A supersonic laser ablation beam source with narrow velocity spreads.

A supersonic beam source for SrF and BaF molecules is constructed by combining the expansion of carrier gas (a mixture of 2% SF6 and 98% argon) from an Even-Lavie valve with laser ablation of a barium/strontium metal target at a repetition rate of 10 Hz. Molecular beams with a narrow translational velocity spread are produced at relative values of Δv/v = 0.053(11) and 0.054(9) for SrF and BaF, respectively. The relative velocity spread of the beams produced in our source is lower in comparison with the results from other metal fluoride beams produced in supersonic laser ablation sources. The rotational temperature of BaF is measured to be 3.5 K. The source produces 6 × 108 and 107 molecules per steradian per pulse in the X2Σ+ (ν = 0, N = 1) state of BaF and SrF molecules, respectively, a state amenable to Stark deceleration and laser cooling.

Temperature and presence of ethanol affect accumulation of intracellular trehalose in Lactobacillus plantarum WCFS1 upon pulsed electric field treatment.

Pulsed electric field (PEF) treatment can be used to increase intracellular small molecule concentrations in bacteria, which can lead to enhanced robustness of these cells during further processing. In this study we investigated the effects of the PEF treatment temperature and the presence of 8% (v/v) ethanol in the PEF medium on cell survival, membrane fluidity and intracellular trehalose concentrations of Lactobacillus plantarum WCFS1. A moderate PEF treatment temperature of 21 °C resulted in a high cell survival combined with higher intracellular trehalose concentrations compared to a treatment at 10 and 35 °C. Interestingly, highest intracellular trehalose concentrations were observed upon supplementing the PEF medium with 8% ethanol, which resulted in more than a doubling in intracellular trehalose concentrations, while culture survival was retained. Overall, this study shows that treatment temperature and PEF medium optimization are important directions for improving molecule uptake upon PEF processing.

Reversibility of membrane permeabilization upon pulsed electric field treatment in Lactobacillus plantarum WCFS1.

Pulsed electric field (PEF) treatment, or electroporation, can be used to load molecules into cells. The permeabilizing effect of the PEF treatment on the cellular membrane can be either reversible or irreversible depending on the severity of the PEF treatment conditions. The influence of PEF on the reversibility of membrane permeabilization in Lactobacillus plantarum WCFS1 by two different fluorescent staining methods was investigated in this study. Whereas staining with propidium iodide (PI) before and after PEF treatment indicated small reversible permeabilized fractions of maximum 14%, the use of a double staining method with PI and SYTOX Green suggested larger reversible permeabilized fractions up to 40% of the population. This difference shows that the choice for a fluorescent staining method affects the conclusions drawn regarding reversibility of membrane permeabilization. Additionally, the effect of PEF treatment conditions on membrane integrity was compared, indicating a relation between critical electric field strength, cell size and membrane permeabilization. Overall this study showed the possibilities and limitations of fluorescent membrane integrity staining methods for PEF studies.

Baryon-Number Violation by Two Units and the Deuteron Lifetime.

We calculate the lifetime of the deuteron with dimension-nine quark operators that violate baryon number by two units. We construct an effective field theory for |ΔB|=2 interactions that give rise to neutron-antineutron (n-n[over ¯]) oscillations and dinucleon decay within a consistent power counting. We calculate the ratio of the deuteron lifetime to the square of the n-n[over ¯] oscillation time up to next-to-leading order. Our result, which is analytical and has a quantified uncertainty, is smaller by a factor ≃2.5 than earlier estimates based on nuclear models, which impacts the indirect bound on the n-n[over ¯] oscillation time and future experiments. We discuss how combined measurements of n-n[over ¯] oscillations and deuteron decay can help to identify the sources of baryon-number violation.

Moderate intensity Pulsed Electric Fields (PEF) as alternative mild preservation technology for fruit juice.

Moderate intensity Pulsed Electric Fields (PEF) was studied for microbial inactivation as an alternative to high intensity PEF or to classical thermal pasteurization. The process is characterized by the application of electric pulses, allowing an increase of the product temperature by the ohmic heat generated by the pulses. A systematic evaluation of the effect of parameters electric field strength (E) and pulse width (τ) on the inactivation of Escherichia coli, Listeria monocytogenes, Lactobacillus plantarum, Salmonella Senftenberg and Saccharomyces cerevisiae in orange juice was carried out in a continuous flow system. A wide range of conditions was evaluated, and both E and τ were shown to be important in the efficacy to inactivate micro-organisms. Remarkably, PEF conditions at E = 2.7 kV/cm and τ = 15-1000 µs showed to be more effective in microbial inactivation than at E = 10 kV/cm and τ = 2 µs. Inactivation kinetics of the tested PEF conditions were compared to an equivalent thermal process to disentangle non-thermal effects (electroporation) from thermal effects responsible for the microbial inactivation. At standard high intensity PEF treatment a non-thermal inactivation at E = 20 kV/cm and τ = 2 µs pulses was observed and attributed to electroporation. Non-thermal effects could also be resolved with moderate intensity PEF at E = 2.7 kV/cm and pulse width between τ = 15-1000 µs. Microbial inactivation at these moderate intensity PEF conditions was studied in more detail at different pH and medium conductivity for E. coli and L. monocytogenes in watermelon juice and coconut water. Under moderate intensity PEF conditions the effectiveness of treatment was independent of pH for all evaluated matrices in the pH range of 3.8-6.0, whereas under high intensity PEF conditions the pH of the product is a critical factor for microbial inactivation. This suggests that the inactivation proceeds through a different mechanism at moderate intensity PEF, and speculations for this mechanism are presented. In conclusion, moderate intensity PEF conditions at E = 2.7 kV/cm and pulse width of 15-1000 µs has potential for industrial processing for the preservation of fruit juices and pH neutral liquid food products.

De novo variants in CDK13 associated with syndromic ID/DD: Molecular and clinical delineation of 15 individuals and a further review.

De novo variants in the gene encoding cyclin-dependent kinase 13 (CDK13) have been associated with congenital heart defects and intellectual disability (ID). Here, we present the clinical assessment of 15 individuals and report novel de novo missense variants within the kinase domain of CDK13. Furthermore, we describe 2 nonsense variants and a recurrent frame-shift variant. We demonstrate the synthesis of 2 aberrant CDK13 transcripts in lymphoblastoid cells from an individual with a splice-site variant. Clinical characteristics of the individuals include mild to severe ID, developmental delay, behavioral problems, (neonatal) hypotonia and a variety of facial dysmorphism. Congenital heart defects were present in 2 individuals of the current cohort, but in at least 42% of all known individuals. An overview of all published cases is provided and does not demonstrate an obvious genotype-phenotype correlation, although 2 individuals harboring a stop codons at the end of the kinase domain might have a milder phenotype. Overall, there seems not to be a clinically recognizable facial appearance. The variability in the phenotypes impedes an à vue diagnosis of this syndrome and therefore genome-wide or gene-panel driven genetic testing is needed. Based on this overview, we provide suggestions for clinical work-up and management of this recently described ID syndrome.

Evaluation of the Gauss-Eyring model to predict thermal inactivation of micro-organisms at short holding times.

Application of mild (non)-thermal processing technologies have received considerable interest as alternative to thermal pasteurisation, because of its shorter holding time and lower temperature aiming for an improved product quality. To understand and develop these alternative technologies, like pulsed electric fields, a proper comparison between the conventional thermal and alternative process is necessary. Up to recent, no suitable models were available to predict the inactivation of micro-organisms by a thermal process at a chosen short holding time, due to non-linearity. The recently developed Gauss-Eyring model with two variables temperature and time has the properties to be a suitable model to apply for short holding times, and was tested for this purpose. Therefore, this study aims to validate if the Gauss-Eyring model can be used to describe non-linear isothermal (a fixed temperature with varying holding time) and isotime (a fixed holding time with varying temperature) thermal inactivation data, and if it is a suitable model to predict the thermal inactivation as a function of temperature for short holding times. Inactivation data of Escherichia coli, Listeria monocytogenes, Lactobacillus plantarum, Salmonella Senftenberg and Saccharomyces cerevisiae in orange juice were collected via isothermal and isotime inactivation kinetics. Survival of the tested micro-organisms was modelled with the Gauss-Eyring model, which contains three parameters σ, Tr and Z. The transition of 'no inactivation' to 'inactivation' (i.e. the 'shoulder' in inactivation curves) can be characterised as the temperature-time (T,t) combination where T=Tr-Z·log10(t), with Tr as the reference temperature defined for 1s treatment, Z as the temperature needed for a 10-fold increase of decrease of the holding time t, and σ as the temperature width of the distribution. The Gauss-Eyring model fitted well to the experimental data, and revealed different sensitivity for the tested micro-organisms. Based on the parameter estimations, survival curves for the desired short holding times were predicted.

The Gauss-Eyring model: A new thermodynamic model for biochemical and microbial inactivation kinetics.

A new primary model has been developed, using Gaussian distributed populations and Eyrings rate constant for the transition state, to describe inactivation kinetics of enzymes and micro-organisms subjected to heat and chemical treatment. The inactivation of both enzymes and micro-organisms could be associated with the irreversible transition to an inactivated state, as suggested by the Lumry-Eyring model for protein denaturation and enzyme inactivation. The characteristic inactivation model parameters, standard activation enthalpy and entropy, are directly related to the reference temperature and Z-value commonly used for kinetic analysis in food microbiology. An essential feature of the kinetic model is that its parameters, and hence the transition temperature, are treated as stochastic variables. The characteristic line shape of the primary model is the log-normal distribution. The performance of the model was validated, using literature data for enzyme and microbial inactivation over a wide range of temperature and pH.

Effect of electrical field strength applied by PEF processing and storage temperature on the outgrowth of yeasts and moulds naturally present in a fresh fruit smoothie.

Pulsed electrical field (PEF) technology offers an alternative to thermal pasteurisation of high-acid fruit juices, by extending the shelf life of food products, while retaining its fresh taste and nutritional value. Substantial research has been performed on the effect of electrical field strength on the inactivation kinetics of spoilage and pathogenic micro-organisms and on the outgrowth of spoilage micro-organisms during shelf life. However, studies on the effect of electrical field strength on the inactivation and outgrowth of surviving populations during shelf life are missing. In this study, we assessed the influence of electrical field strength applied by PEF processing and storage temperature on the outgrowth of surviving yeast and mould populations naturally present in fresh fruit smoothie in time. Therefore, an apple-strawberry-banana smoothie was treated in a continuous-flow PEF system (130L/h), using similar inlet and outlet conditions (preheating temperature 41°C, maximum temperature 58°C) to assure that the amount of energy across the different conditions was kept constant. Smoothies treated with variable electrical field strengths (13.5, 17.0, 20.0 and 24.0kV/cm) were compared to smoothies without treatment for outgrowth of yeasts and moulds. Outgrowth of yeasts and moulds stored at 4°C and 7°C was analysed by plating and visual observation and yeast growth was modelled using the modified logistic growth model (Zwietering model). Results showed that the intensity of the electrical field strength had an influence on the degree of inactivation of yeast cells, resulting in a faster outgrowth over time at lower electrical field strength. Outgrowth of moulds over time was not affected by the intensity of the electrical field strength used. Application of PEF introduces a trade-off between type of spoilage: in untreated smoothie yeasts lead to spoilage after 8days when stored at 4 or 7°C, whereas in PEF treated smoothie yeasts were (partly) inactivated and provided outgrowth opportunities for moulds, which led to spoilage by moulds after 14days (7°C) or 18days (4°C).

Mountain time trial in handcycling: exercise intensity and predictors of race time in people with spinal cord injury.

STUDY DESIGN: Cross-sectional analyses. OBJECTIVES: To analyze exercise intensity during a mountain time trial in handcycling and to determine predictors of race time. SETTING: Eight Dutch rehabilitation centers and Austrian mountain. METHODS: Forty participants with spinal cord injury (SCI; high lesion level (>T6): N=11; low lesion level (⩽T6): N=29) handcycled a 20.2-km mountain time trial. Heart rate (HR) was monitored in 17 (high: N=5, low: N=12) participants during the race to determine exercise intensity, expressed relative to the heart rate reserve (%HRR). Two weeks before the race all participants completed laboratory tests to measure anthropometrics and peak values for power output (POpeak), oxygen uptake (VO2peak) and HR. RESULTS: Mean race time was 4 h and 1 min (s.d.: 1 h and 24 min), with no difference in race time between lesion groups. Mean exercise intensity during the race was 70±7%HRR. Exercise was mainly (73% of the race time) at a vigorous intensity (60-89%HRR), with 29% of the total time in the 80-89%HRR zone. No clear differences were found in exercise intensities between lesion groups. The strongest predictors for better race times were higher mean %HRR during race (R(2)=57%), lower waist circumference (R(2)=39%), higher POpeak (R(2)=39%) and VO2peak (R(2)=32%). CONCLUSION: A 20-km mountain time trial in a handcycle is intensive. Faster race times were achieved by those with a lower waist circumference, greater fitness level and ability to perform at higher average exercise intensities during the race. Level of SCI was not significantly associated with race time.

Pulsed electric field processing of different fruit juices: impact of pH and temperature on inactivation of spoilage and pathogenic micro-organisms.

Pulsed electrical field (PEF) technology can be used for the inactivation of micro-organisms and therefore for preservation of food products. It is a mild technology compared to thermal pasteurization because a lower temperature is used during processing, leading to a better retention of the quality. In this study, pathogenic and spoilage micro-organisms relevant in refrigerated fruit juices were studied to determine the impact of process parameters and juice composition on the effectiveness of the PEF process to inactivate the micro-organisms. Experiments were performed using a continuous-flow PEF system at an electrical field strength of 20 kV/cm with variable frequencies to evaluate the inactivation of Salmonella Panama, Escherichia coli, Listeria monocytogenes and Saccharomyces cerevisiae in apple, orange and watermelon juices. Kinetic data showed that under the same conditions, S. cerevisiae was the most sensitive micro-organism, followed by S. Panama and E. coli, which displayed comparable inactivation kinetics. L. monocytogenes was the most resistant micro-organism towards the treatment conditions tested. A synergistic effect between temperature and electric pulses was observed at inlet temperatures above 35 °C, hence less energy for inactivation was required at higher temperatures. Different juice matrices resulted in a different degree of inactivation, predominantly determined by pH. The survival curves were nonlinear and could satisfactorily be modeled with the Weibull model.

Limits on Lorentz violation from forbidden ß decays.

Forbidden (slow) ß decays offer new opportunities to test the invariance of the weak interaction under Lorentz transformations. Within a general effective field theory framework we analyze and reinterpret the only two relevant experiments, performed in the 1970s, dedicated to search for a preferred direction in space in first- and second-forbidden ß decays. We show that the results of these experiments put strong and unique limits on Lorentz violation, and in particular on the presence of several interactions in the modern Lorentz-violating standard model extension. We discuss prospects to improve on these limits.

P and T violating form factors of the deuteron.

We calculate the electric-dipole and magnetic-quadrupole form factors of the deuteron that arise as a low-energy manifestation of parity and time-reversal violation in quark-gluon interactions. We consider the QCD vacuum angle and the dimension-six operators that originate from physics beyond the standard model: the quark electric and chromoelectric dipole moments and the gluon chromoelectric dipole moment. Within the framework of two-flavor chiral perturbation theory, we show that in combination with the nucleon electric dipole moment, the deuteron moments would allow an identification of the dominant source(s) of symmetry violation.

Home treatment with enzyme replacement therapy for mucopolysaccharidosis type I is feasible and safe.

OBJECTIVE: Intravenous enzyme replacement therapy (ERT) with recombinant alpha-L-iduronidase may ameliorate the non-neurological symptoms in patients with mucopolysaccharidosis type I (MPS I). Since home-based ERT for Gaucher and Fabry diseases has been reported to be safe and successful, we investigated the feasibility and safety of home therapy in patients with MPS I. SETTING: This two-centre study included 17 ERT-treated MPS I patients between 1 and 35 years of age. A patient was allowed to transfer to home treatment after a minimum period of 6 months of in-hospital administration of ERT and after a self- or home nurse-supported home setting was arranged. RESULTS: Thirteen out of 17 patients transferred to home treatment with a median time to transfer of 13 months (range 7-40 months). Two patients preferred to continue ERT in the hospital, whereas for two other patients the transfer to home was hampered for practical reasons. All patients who received ERT at home were assisted by either a relative or a nurse. In total over 1000 home infusions were performed and no serious complications were observed. Two infusion-associated reactions were observed, both within the first 3 months of in-hospital administration of ERT. All patients except one developed antibodies against the recombinant enzyme, but this was not associated with the development of hypersensitivity reactions. CONCLUSION: ERT for MPS I applied at home is safe and might alleviate the burden of life-long intravenous treatment in these patients.

Cardiac abnormalities in adults with the attenuated form of mucopolysaccharidosis type I.

BACKGROUND: Cardiac involvement in mucopolysaccharidosis type I (MPS I) has been studied primarily in its most severe forms. Cardiac involvement, particularly left ventricular (LV) systolic and diastolic function, in the attenuated form of MPS I is less well known. METHODS: Cardiac function was prospectively investigated in 9 adult patients with the attenuated form of MPS I. All patients underwent 12-lead electrocardiography, 24 h Holter monitoring and two-dimensional echocardiography including tissue Doppler imaging (TDI). Eighteen age- and sex-matched healthy volunteers served as a control group. RESULTS: Aortic, mitral and tricuspid valve thickening was seen in, respectively, 5 (56%), 4 (44%) and 2 (22%) patients. Moderate mitral valve stenosis was seen in 1 patient and moderate aortic stenosis in 2 patients. All patients had mild-to-moderate aortic and mitral valve regurgitation and 6 patients (67%) had mild-to-moderate tricuspid valve regurgitation. Despite normal LV dimensions, ejection fraction and mass index, MPS patients had lower mean systolic mitral annular velocities (6.1 +/- 0.6 vs 9.1 +/- 1.4 cm/s, p < 0.01) compared to normal control subjects. Similarly, mean early diastolic mitral annular velocities were lower in MPS patients (7.8 +/- 0.9 vs 13.3 +/- 3.3 cm/s, p < 0.01). CONCLUSION: MPS I patients with the attenuated phenotype have not only valvular abnormalities but also LV diastolic and systolic abnormalities.

[Insulin resistance: the role of intramuscular triglyceride and the importance of physical activity]. / Insulineresistentie: de rol van intramusculair triacylglycerol en het nut van fysieke inspanning.

In the Netherlands, the prevalence of diabetes is expected to rise from 480,000 to more than 650,000 patients by the year 2020. Numerous studies have reported a strong correlation between elevated plasma-free fatty-acid levels, the accumulation of intramuscular triglyceride (IMTG) and the development of insulin resistance. Traditionally, the Randle cycle was used to explain the mechanism behind fatty acid-induced insulin resistance in skeletal muscle. An alternative explanation is that the increased supply of free fatty acids leads to the accumulation of IMTG and fatty-acid metabolites, which can induce defects in the insulin signalling cascade, causing insulin resistance in skeletal muscle. However, this proposed relationship between elevated IMTG concentrations and skeletal-muscle insulin resistance does not always apply, as trained athletes have been shown to be markedly insulin-sensitive, despite having high levels of stored IMTG. This metabolic paradox is explained by the fact that it is not the size of the IMTG pool but rather the balance between fatty-acid availability, uptake and oxidation, i.e. the low turnover of the IMTG pool, that is instrumental in the development of skeletal-muscle insulin resistance. Physical exercise forms an effective strategy to improve the balance between skeletal-muscle fatty-acid uptake and oxidation and, as such, can prevent the development of skeletal-muscle insulin resistance.

Coherent bremsstrahlung in the alpha + p system at 50 MeV/nucleon

Photons originating from coherent bremsstrahlung have been measured over a large dynamic range for the reaction of 200 MeV alpha particles with protons. At low photon energies the bremsstrahlung spectrum exhibits the classical behavior with an approximate 1/E(gamma) shape. At higher photon energies there is a pronounced contribution from capture into the unbound ground state and first excited state of 5Li. These results allow one, for the first time, to test theoretical models for a consistent description of bremsstrahlung and radiative capture in a complex system. Calculations predict both features qualitatively but fail to account for their relative importance.

Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients.

OBJECTIVES: The study examined the value of contrast echocardiography in the assessment of left ventricular (LV) wall motion in intensive care unit (ICU) patients. BACKGROUND: Echocardiograms done in the ICU are often suboptimal. The most common indication is the evaluation of LV wall motion and ejection fraction (EF). METHODS: Transthoracic echocardiograms were done in 70 unselected ICU patients. Wall motion was evaluated on standard echocardiography (SE), harmonic echocardiography (HE), and after intravenous (IV) contrast echocardiography (CE) using a score for each of 16 segments. A confidence score was also given for each segment with each technique (unable to judge; not sure; sure). The EF was estimated visually for each technique, and a confidence score was applied to the EF. RESULTS: Uninterpretable wall motion was present in 5.4 segments/patient on SE, 4.4 on HE (p = 0.2), and 1.1 on CE (p < 0.0001). An average of 7.8 segments were read with surety on SE, 9.2 on HE (p = 0.1), and 13.7 on CE (p < 0.0001). Ejection fraction was uninterpretable in 23% on SE, 13% on HE (p = 0.14), and 0% on CE (p = 0.002 vs. HE; p < 0.0001 vs. SE). The EF was read with surety in 56% of patients on SE, 62% on HE (p = 0.47), and 91% on CE (p < 0.0001). Thus, wall motion was seen with more confidence on CE. More importantly, the actual readings of segmental wall motion and EF significantly differed using CE. CONCLUSIONS: CE should be used in all ICU patients with suboptimal transthoracic echocardiograms.