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Contains fulltext : 291333.pdf (Publisher’s version ) (Open Access) To optimize care for children with Marfan syndrome (MFS) in the Netherlands, Dutch MFS growth charts were constructed. Additionally, we aimed to investigate the effect of FBN1 variant type (haploinsufficiency [HI]/dominant negative [DN]) on growth, and compare MFS-related height increase across populations. Height and weight data of individuals with MFS aged 0-21 years were retrospectively collected. Generalized Additive Models for Location, Scale and Shape (GAMLSS) was used for growth chart modeling. To investigate genotype-phenotype relationships, FBN1 variant type was included as an independent variable in height-for-age and BMI-for-age models. MFS-related height increase was compared with that of previous MFS growth studies from the United States, Korea, and France. Height and weight data of 389 individuals with MFS were included (210 males). Height-for-age, BMI-for-age, and weight-for-height charts reflected the tall and slender MFS habitus throughout childhood. Mean increase in height of individuals with MFS compared with the general Dutch population was significantly lower than in the other three MFS populations compared to their reference populations. FBN1-HI variants were associated with taller height in both sexes, and decreased BMI in females (p-values

Type II toxin–antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specificity of an array of diverse GNAT toxins. Our functional data show that the majority of GNAT toxins are specific to Gly-tRNA isoacceptors. However, the phylogenetic analysis shows that the ancestor of GNAT toxins was likely a relaxed specificity enzyme capable of acetylating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.

Toxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented inMycobacterium tuberculosis(Mtb), their individual physiological roles remain elusive. We describe a TA system inMtbwhich we have named TacAT due to its homology to previously discovered systems in Salmonella. The toxin, TacT, blocks growth by acetylating glycyl-tRNAs and inhibiting translation. Its effects are reversed by the enzyme peptidyl tRNA hydrolase (Pth), which also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. Pth is essential in most bacteria and thereby has been proposed as a promising drug target for complex pathogens likeMtb. Transposon sequencing data suggest that thetacAToperon is nonessential forMtbgrowthin vitro, and premature stop mutations in this TA system present in some clinical isolates suggest that it is also dispensablein vivo. We assessed whether TacT modulatespthessentiality inMtb, as drugs targeting Pth might be ineffective if TacAT is disrupted. We find thatpthessentiality is unaffected by the absence oftacAT. These results highlight a fundamental aspect of mycobacterial biology and indicate that Pth’s essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth’s potential as a viable target for new antibiotics.

The atmospheric aerosol has a large influence on global climate through its ability of scattering and absorbing electromagnetic radiation, which affect the Earth's radiative balance. Characteristics, such as size distribution, chemical composition and hygroscopic properties are important for improving global climate model projections of natural sea spray aerosols, which are numerically dominant in the global aerosol budget. Previous experimental studies in coastal locations revealed a complex mixing between natural and anthropogenic aerosols. This complexity makes it difficult to characterize the behavior of natural sea spray aerosols in a simplified form that is suitable for global models. The aim of the present paper is to characterize the size distributions of natural sea spray aerosols at a coastal site in False Bay, South Africa. The opening of False Bay towards the Southern Ocean with unlimited fetch from Antarctica provides a unique opportunity to measure and focus on pristine marine air masses solely. A large observational data set from the First European-South African Transmission Experiment (FESTER) was analyzed and two case studies are presented to illustrate the contribution of sea spray to aerosol size distributions under pure marine and mixed air mass conditions, respectively. A set of conditions for measuring pure marine aerosols in False Bay was established. The results of the relationship of aerosol concentrations with wind speed reveals the distinct behavior of natural sea spray aerosols and demonstrates the pure marine influence of the Southern Ocean in False Bay. Comparison of the aerosol size distributions to a coastal site in the Mediterranean Sea, attest to the contribution of sea spray to aerosol size distributions in False Bay.

This paper discusses the use of smoke obscurants as countermeasures against high energy lasers (HEL). Potential success of the smoke does not depend only the performance of the smoke. The transmission loss in the smoke is part of a chain of system components, including warning sensors, smoke launchers, etc.. The core of the paper deals with experimental work on the following research questions: - Does smoke attenuate an incoming beam of a HEL? - Does the HEL affect the smoke itself? The experimental set-up with the TNO 30kW HEL and the scale model for the smoke transmission path will be shown. Selected experimental results will be shown and discussed. Finally we will compare the results to theoretical calculations and we will analyze the properties of an ideal HEL attenuation smoke.

We report the analysis of radio soundings launched at our permanent measurement site in North-western Germany. The data of potential temperature and wind speed are used to derive vertical profiles of the gradient Richardson number 𝑅𝑖𝑔 in the free troposphere, and subsequently, the strength of optical turbulence 𝐶𝑛 2. These values are compared to a numerical framework, which derives 𝐶𝑛 2 from mesoscale weather prediction data by two schemes based on the gradient Richardson number and Monin-Obukhov similarity theory, respectively.

We investigate the effects of wind–wave interactions on the surface sea-spray-generation flux. To this end, the Marine Aerosol Tunnel Experiment (MATE2019) was conducted at the Pytheas Institute large wave–wind facility in Luminy (Marseille, France) over the period June–July 2019. A unique range of air–sea boundary conditions was generated by configuring the laboratory with four types of wave forcing and five wind speeds spanning 8–20 m s $$^{-1}$$ . Young and developed waves were included, with wave ages between 1.3 and 9.5 (defined in terms of phase speed and friction velocity). Vertical sea-spray-concentration profiles measured over the 0.1–47.5 $$\upmu $$ m radius range and a flux–profile method allowed estimation of the sea-spray-generation flux. Results show that the flux increases for increased wind-induced wave breaking, and is highest for steep and heavily-breaking waves. Scaling analysis shows that the sea-spray generation is best correlated with the wave-slope variance for larger droplets (20 $$\upmu $$ m and above, assumed predominantly spume droplets generated by surface tearing). For smaller droplets (7–20 $$\upmu $$ m, presumed predominantly jet droplets generated by bubble bursting), the highest correlation is found with a non-dimensional number combining the wave-slope variance with the friction velocity cubed. This is reflected in the formulation of two wave-state-dependent sea-spray-generation functions, each valid for wind speeds 12–20 m s $$^{-1}$$ and droplet radii 3–35 $$\upmu $$ m, thereby covering jet and spume droplet production.

Contains fulltext : 234969.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: Standard treatment for naïve hereditary hemochromatosis patients consists of phlebotomy or a personalized erythrocytapheresis. Erythrocytapheresis is more efficient, but infrequently used because of perceived costs and specialized equipment being needed. The main aim of our study was to develop a model that predicts the number of initial treatment procedures for both treatment methods. This information may help the clinician to select the optimal treatment modality for the individual patient. METHODS: We analyzed retrospective data of 125 newly diagnosed patients (C282Y homozygous), treated either with phlebotomy (n = 54) or erythrocytapheresis (n = 71) until serum ferritin (SF) reached levels ≤100 μg/L. To estimate the required number of treatment procedures multiple linear regression analysis was used for each treatment method separately. RESULTS: The linear regression model with the best predictive quality (R(2) = 0.74 and 0.73 for erythrocytapheresis and phlebotomy respectively) included initial SF, initial hemoglobin (Hb) level, age, and BMI, where initial SF was independently related to the total number of treatment procedures for both treatment methods. The prediction error expressed in RMSPE and RMSDR was lower for erythrocytapheresis than for phlebotomy (3.8 and 4.1 vs 7.0 and 8.0 respectively), CONCLUSIONS: Although the prediction error of the developed model was relatively large, the model may help the clinician to choose the most optimal treatment method for an individual patient. Generally erythrocytapheresis halves the number of treatment procedures for all patients, where the largest reduction (between 55% and 64%) is reached in patients with an initial Hb level ≥ 9 mmol/L (14.5 g/dL). ClinicalTrials.gov number NCT00202436.

Recent studies stress the importance of considering sea surface wave characteristics in sea spray generation functions (SSGFs). To this end, the effect of interacting winds and waves on sea spray generation was studied using data collected during the Marine Aerosol Tunnel Experiments (MATE2019) conducted at the OSU-Pytheas large wind-wave tunnel facility at Luminy, Marseille (France) (Study detailed in Bruch et al., in review). A total of 20 wind and wave combinations were tested, with wind speeds between 8 and 20 m s-1 combined with pure wind waves and waves generated by a wavemaker, allowing for a range of wave characteristics and wave ages. Similar wind speed profiles and whitecapping behavior between the laboratory and the field suggest that the laboratory is appropriate for the study of sea spray production. The sea spray generation flux was estimated from logarithmic vertical sea spray concentration profiles using a flux-profile method using Monin and Obukhov (1954) theory. Results show that the production of larger droplets at 20-35 µm radius is well correlated with the wave slope variance 2>, whilst the wind friction velocity cubed u*3 performs best over 7-20 µm. Two SSGFs are proposed. The original work presented here is an assessment of the validity of the two SSGFs in the field. The two laboratory-derived SSGFs are tested in two numerical models; the stationary Marine Aerosol Concentration Model (MACMod) (used in Laussac et al., 2018), and the non-hydrostatic mesocale atmospheric model Meso-NH (jointly developed by the LA - UMR 5560 - and the CNRM - UMR 3589). The 2> necessary required by both SSGFs is estimated using a wind-dependent formulation (Cox and Munk, 1956) and a spectral spectral model (Elfouhaily et al., 1997). Results show that the numerical simulations offer good results relative to sea spray measurements obtained in the North-West Mediterranean in fetch-limited conditions (Laussac et al., 2018), as well as other existing SSGFs in the literature. These results suggest that wind-wave tunnel facilities present an interesting alternative for determining the sea spray generation flux, especially in high wind speed conditions in which deployment in the field is difficult.References :Bruch, W., Piazzola, J., Branger, H., van Eijk, A. M. J., Luneau, C., Bourras, D., Tedeschi, G. (In review). Sea Spray Generation Dependence on Wind and Wave Combinations : A Laboratory Study. Submitted in : Boundary Layer Meteorology.Cox, C., & Munk, W. (1956). Slopes of the sea surface deduced from photographs of sun glitter. University of California Press. Vol. 6,9,401-488.Elfouhaily, T., Chapron, B., Katsaros, K., & Vandemark, D. (1997). A unified directional spectrum for long and short wind driven waves. Journal of Geophysical Research: Oceans, 102(C7),15781-15796.Monin, A. S., & Obukhov, A. M. (1954). Basic laws of turbulent mixing in the surface layer of the atmosphere. Contrib. Geophys. Inst. Acad. Sci. USSR,151(163),e187.Laussac, S., Piazzola, J., Tedeschi, G., Yohia, C., Canepa, E., Rizza, U., & Van Eijk, A. M. J. (2018). Development of a fetch dependent sea-spray source function using aerosol concentration measurements in the North-Western Mediterranean. Atmospheric Environment,193,177-189.