CTCF-mediated topological boundaries during development foster appropriate gene regulation

The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains within the nucleus. Therefore, CTCF boundaries are not merely static structural components of the genome but instead are locally dynamic regulatory structures that control gene expression during development

Optimization Study of Beam Position and Angular Jitter Independent Bunch Length Monitor for Awake Run 2

In this paper, a study using the Polarization Current Approach (PCA) model is performed to optimize the design of a short bunch length monitor using two dielectric radiators that produce coherent Cherenkov Diffraction Radiation (ChDR). The electromagnetic power emitted from each radiator is measuring a different part of the bunch spectrum using Schottky diodes. For various bunch lengths, the coherent ChDR spectrums are calculated to find the most suitable frequency bands for the detection system. ChDR intensities measured by each detector are estimated for different impact parameters to explore the dependence of bunch length monitor on beam position and angular jitter. It is found that, in the present configuration, the effects of beam position and angular jitter are negligibly small for bunch length measurement

Model-based meta-analysis of salbutamol pharmacokinetics and practical implications for doping control.

Salbutamol was included in the prohibited list of the World Anti-Doping Agency (WADA) in 2004. Although systemic intake is banned, inhalation for asthma is permitted but with dosage restrictions. The WADA established a urinary concentration threshold to distinguish accordingly prohibited systemic self-administration from therapeutic prescription by inhalation. This study aimed at evaluating the ability of the WADA threshold to differentiate salbutamol therapeutic use from violation of antidoping rules. Concentration-time profile of salbutamol in plasma and its excretion in urine was characterized through a model-based meta-analysis of individual and aggregate data collected after administration of a large range of doses following different modes of administration and under a variety of conditions. The developed model adequately fitted salbutamol plasma and urine concentration-time profiles of the 13 selected studies. Model-based simulations confirmed that a wide range of salbutamol urine concentrations might be measured after drug intake. Although violation of the WADA Code can be strongly suspected in individuals showing very high salbutamol urine concentrations, uncertainty remains for values close to the WADA threshold as they can be compatible with both permitted therapeutic use and violation. Although not entirely discriminant, the current WADA rule is globally supported by our appraisal. It could be further improved by a slight and reasonable adjustment of inhaled daily dosages allowed for therapeutic use. Our model might help antidoping experts in the evaluation of suspected doping cases through confronting the athlete's urine measurements with their allegations about salbutamol treatment

Commissioning of the electron injector for the AWAKE experiment

The advanced wakefield experiment (AWAKE) at CERN is the first proton beam-driven plasma wakefield acceleration experiment. The main goal of AWAKE RUN 1 was to demonstrate seeded self-modulation (SSM) of the proton beam and electron witness beam acceleration in the plasma wakefield. For the AWAKE experiment, a 10-meter-long Rubidium-vapor cell together with a high-power laser for ionization was used to generate the plasma. The plasma wakefield is driven by a 400 GeV/c proton beam extracted from the super proton synchrotron (SPS), which undergoes a seeded self-modulation process in the plasma. The electron witness beam used to probe the wakefields is generated from an S-band RF photo-cathode gun and then accelerated by a booster structure up to energies between 16 and 20 MeV. The first run of the AWAKE experiment revealed that the maximum energy gain after the plasma cell is 2 GeV, and the SSM mechanism of the proton beam was verified. In this paper, we will present the details of the AWAKE electron injector. A comparison of the measured electron beam parameters, such as beam size, energy, and normalized emittance, with the simulation results was performed

Slug monitoring and impacts on the ground beetle community in the frame of sustainable pest control in conventional and conservation agroecosystems

In conservation agriculture, slugs are considered significant pests and their monitoring is a key option in the integrated pest management framework. Together with molluscicide applications, predators such as ground beetles can offer a tool for slug control in the field. Through the evaluation of slug and ground beetle monitoring strategies, this work compared their presence in conventional and conservation agricultural plots. The invasive Deroceras invadens was the dominant slug species to occur in all sampling periods. Among Carabidae, Poecilus cupreus and Pterostichus melas were the most abundant species, and Bembidion spp., Brachinus spp., and Harpalus spp. were also common. Beer-baited pitfall traps, whatever their alcoholic content, caught more slugs and ground beetles than wooden boards used as shelters. Slugs were more abundant in conventional plots than in conservation plots, possibly due to the lower presence of natural enemies such as ground beetles. Despite possible impacts on Carabidae, beer-baited pitfall traps should be considered a useful tool for slug monitoring and for the planning of molluscicide applications. Soil management such as minimum-or no-tillage and the presence of cover crops are important elements influencing both slug and ground beetle presence, possibly playing a key role in the maintenance of natural enemy populations

Pyrethroid resistance in Italian populations of the mite Varroa destructor: a focus on the Lombardy region

Varroa destructor Anderson et Trueman (Acari Varroidae) is a major pest of honey bees and synthetic acaricide treatments remain the most effective tool to contain its infestations. In 1991, pyrethroid resistance was first reported in Lombardy, and is now spread worldwide. Recently, three different mutations (L925V/I/M) occurring in the voltage-gated sodium channel have been associated with tau-fluvalinate resistance. Furthermore, in the literature, indirect evidence from laboratory bioassays have indicated that high levels of esterases may be involved in mites resistant to tau-fluvalinate. This study provides an update on the actual spread of target-site resistance to tau-fluvalinate in V. destructor samples collected in the Lombardy region. TaqMan assays showed that mutation L925V is present in this area, however only low frequencies of this resistant allele were detected. The majority of resistant mites were found in the homozygous form (11%), and only a small fraction possessed the heterozygous genotype (2%). Additionally, a protocol was set up to detect esterase activity directly in single mites. Slight variability was observed among different populations collected in Lombardy. Additional studies are needed to confirm the involvement of esterases in resistance to pyrethroids in V. destructor and whether this can be correlated to changes in enzyme activity

Generalised hydrodynamics of TT-deformed integrable quantum field theories

In this paper we evaluate the averages of conserved densities and currents associated to charges of generic spin in (1+1)-dimensional massive integrable Quantum Field Theories perturbed by the irrelevant TT operator. By making use of the Thermodynamic Bethe Ansatz approach and of the theory of Generalised Hydrodynamics, we study the non-equilibrium steady state averages of conserved densities and currents in a partitioning protocol. We show that, in particular limits, averages can be evaluated exactly in terms of quantities known from the unperturbed theory. In the massless limit we recover known results for the energy and momentum currents and generalise those to any higher spin conserved quantities. We extend some of our results to perturbations of the generalised TT type. For the massive free fermion theory, we find an analytic expression for the effective inverse temperature after at TT perturbation in terms of the bare inverse temperature by making use of Lambert’s W function

Lineage-based identification of cellular states and expression programs

We present a method, LineageProgram, that uses the developmental lineage relationship of observed gene expression measurements to improve the learning of developmentally relevant cellular states and expression programs. We find that incorporating lineage information allows us to significantly improve both the predictive power and interpretability of expression programs that are derived from expression measurements from in vitro differentiation experiments. The lineage tree of a differentiation experiment is a tree graph whose nodes describe all of the unique expression states in the input expression measurements, and edges describe the experimental perturbations applied to cells. Our method, LineageProgram, is based on a log-linear model with parameters that reflect changes along the lineage tree. Regularization with L1 that based methods controls the parameters in three distinct ways: the number of genes change between two cellular states, the number of unique cellular states, and the number of underlying factors responsible for changes in cell state. The model is estimated with proximal operators to quickly discover a small number of key cell states and gene sets. Comparisons with existing factorization, techniques, such as singular value decomposition and non-negative matrix factorization show that our method provides higher predictive power in held, out tests while inducing sparse and biologically relevant gene sets.National Institutes of Health (U.S.) (P01-NS055923)National Institutes of Health (U.S.) (1-UL1-RR024920

Effects of Bioactive Peptides from Atlantic Salmon Processing By-Products on Oxyntopeptic and Enteroendocrine Cells of the Gastric Mucosa of European Seabass and Gilthead Seabream

The present study was designed to evaluate the effects of dietary levels of bioactive peptides (BPs) derived from salmon processing by-products on the presence and distribution of peptic cells (oxyntopeptic cells, OPs) and enteric endocrine cells (EECs) that contain GHR, NPY and SOM in the gastric mucosa of European seabass and gilthead seabream. In this study, 27 seabass and 27 seabreams were divided into three experimental groups: a control group (CTR) fed a control diet and two groups fed different levels of BP to replace fishmeal: 5% BP (BP5%) and 10% BP (BP10%). The stomach of each fish was sampled and processed for immunohistochemistry. Some SOM, NPY and GHR-IR cells exhibited alternating "open type" and "closed type" EECs morphologies. The BP10% group (16.8 ± 7.5) showed an increase in the number of NPY-IR cells compared to CTR (CTR 8.5 ± 4.8) and BP5% (BP10% vs. CTR p ≤ 0.01; BP10% vs. BP5% p ≤ 0.05) in the seabream gastric mucosa. In addition, in seabream gastric tissue, SOM-IR cells in the BP 10% diet (16.8 ± 3.5) were different from those in CTR (12.5 ± 5) (CTR vs. BP 10% p ≤ 0.05) and BP 5% (12.9 ± 2.5) (BP 5% vs. BP 10% p ≤ 0.01). EEC SOM-IR cells increased at 10% BP (5.3 ± 0.7) compared to 5% BP (4.4 ± 0.8) (5% BP vs. 10% BP p ≤ 0.05) in seabass. The results obtained may provide a good basis for a better understanding of the potential of salmon BPs as feed ingredients for seabass and seabream

Long-term bond strength and endogenous enzymatic activity of a chlorhexidine-containing commercially available adhesive

10siObjectives: The aim of this study was to investigate, by the means of microtensile bond strength (μTBS) test, gelatin and in situ zymography, the influence of 0.2% CHX contained within a commercially available adhesive on long-term bond strength and endogenous enzymatic activity. Methods: Non-carious teeth were subjected to μTBS test (N = 15 for each group) and stressed until failure. μTBS was evaluated immediately and after 12-month storage in artificial saliva at 37 °C. Dentin powder was obtained from additional teeth (N = 7) for gelatin zymography, while for in situ zymography, 3 teeth for each group were selected. Gelatin and in situ zymography were performed in dentin powder and slices of dentin, respectively, to assess the ability of 0.2% CHX blended within the adhesive to inhibit endogenous enzymatic activity. Results: μTBS bond strength was higher in the CHX-containing groups, immediately as well as after aging. The bond strength significantly decreased after 12-month aging. The activation of endogenous MMPs was found to be related to the presence of CHX within the adhesive system and the bonding strategy employed. Conclusions: Under this perspective 0.2% CHX blended within Peak Universal adhesive monomer seems to in- crease immediate bond strength, to preserve bond strength over time and to efficiently inhibit endogenous enzymatic activity in dentin. Hence, blending the CHX in low concentrations within the adhesive could be recommended as a feasible technique in every-day clinical practice. Clinical significance: Using CHX-containing adhesives could be recommended due to several benefits: it seems to increase the longevity of the hybrid layer; the inhibitor appears to be efficiently delivered to the dentinal substrate and to inhibit endogenous enzymatic activity, without prolonging chair time.openopenMaravić, Tatjana; Comba, Allegra; Cunha, Sandra Ribeiro; Angeloni, Valeria; Cadenaro, Milena; Visinitini, Erika; Navarra, Chiara Ottavia; Salgarello, Stefano; Breschi, Lorenzo*; Mazzoni, AnnalisaMaravić, Tatjana; Comba, Allegra; Cunha, Sandra Ribeiro; Angeloni, Valeria; Cadenaro, Milena; Visinitini, Erika; Navarra, Chiara Ottavia; Salgarello, Stefano; Breschi, Lorenzo; Mazzoni, Annalis