Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing

Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda-sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda-�� clamp complex. This complex contains two pairs of Hda dimers sandwiched between two �� clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the �� clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda-�� clamp complex indicate that the interaction of the �� clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda-�� clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. ? The Author(s) 2017.113Ysciescopu

Bayesian Nonparametric Inverse Reinforcement Learning

Inverse reinforcement learning (IRL) is the task of learning the reward function of a Markov Decision Process (MDP) given the transition function and a set of observed demonstrations in the form of state-action pairs. Current IRL algorithms attempt to find a single reward function which explains the entire observation set. In practice, this leads to a computationally-costly search over a large (typically infinite) space of complex reward functions. This paper proposes the notion that if the observations can be partitioned into smaller groups, a class of much simpler reward functions can be used to explain each group. The proposed method uses a Bayesian nonparametric mixture model to automatically partition the data and find a set of simple reward functions corresponding to each partition. The simple rewards are interpreted intuitively as subgoals, which can be used to predict actions or analyze which states are important to the demonstrator. Experimental results are given for simple examples showing comparable performance to other IRL algorithms in nominal situations. Moreover, the proposed method handles cyclic tasks (where the agent begins and ends in the same state) that would break existing algorithms without modification. Finally, the new algorithm has a fundamentally different structure than previous methods, making it more computationally efficient in a real-world learning scenario where the state space is large but the demonstration set is small

Supervised Domain Adaptation using Graph Embedding

Getting deep convolutional neural networks to perform well requires a large amount of training data. When the available labelled data is small, it is often beneficial to use transfer learning to leverage a related larger dataset (source) in order to improve the performance on the small dataset (target). Among the transfer learning approaches, domain adaptation methods assume that distributions between the two domains are shifted and attempt to realign them. In this paper, we consider the domain adaptation problem from the perspective of dimensionality reduction and propose a generic framework based on graph embedding. Instead of solving the generalised eigenvalue problem, we formulate the graph-preserving criterion as a loss in the neural network and learn a domain-invariant feature transformation in an end-to-end fashion. We show that the proposed approach leads to a powerful Domain Adaptation framework; a simple LDA-inspired instantiation of the framework leads to state-of-the-art performance on two of the most widely used Domain Adaptation benchmarks, Office31 and MNIST to USPS datasets.Comment: 7 pages, 3 figures, 3 table

Training Hospital Providers in Basic CPR Skills in Botswana: Acquisition, Retention and Impact of Novel Training Techniques

Objective Globally, one third of deaths each year are from cardiovascular diseases, yet no strong evidence supports any specific method of CPR instruction in a resource-limited setting. We hypothesized that both existing and novel CPR training programs significantly impact skills of hospital-based healthcare providers (HCP) in Botswana. Methods HCP were prospectively randomized to 3 training groups: instructor led, limited instructor with manikin feedback, or self-directed learning. Data was collected prior to training, immediately after and at 3 and 6 months. Excellent CPR was prospectively defined as having at least 4 of 5 characteristics: depth, rate, release, no flow fraction, and no excessive ventilation. GEE was performed to account for within subject correlation. Results Of 214 HCP trained, 40% resuscitate ≥1/month, 28% had previous formal CPR training, and 65% required additional skills remediation to pass using AHA criteria. Excellent CPR skill acquisition was significant (infant: 32% vs. 71%, p \u3c 0.01; adult 28% vs. 48%, p \u3c 0.01). Infant CPR skill retention was significant at 3 (39% vs. 70%, p \u3c 0.01) and 6 months (38% vs. 67%, p \u3c 0.01), and adult CPR skills were retained to 3 months (34% vs. 51%, p = 0.02). On multivariable analysis, low cognitive score and need for skill remediation, but not instruction method, impacted CPR skill performance. Conclusions HCP in resource-limited settings resuscitate frequently, with little CPR training. Using existing training, HCP acquire and retain skills, yet often require remediation. Novel techniques with increased student: instructor ratio and feedback manikins were not different compared to traditional instruction

A systematic study of J/psi suppression in cold nuclear matter

Based on a Glauber model, a statistical analysis of all mid-rapidity J/psi hadroproduction and leptoproduction data on nuclear targets is carried out. This allows us to determine the J/psi-nucleon inelastic cross section, whose knowledge is crucial to interpret the J/psi suppression observed in heavy-ion collisions, at SPS and at RHIC. The values of sigma are extracted from each experiment. A clear tension between the different data sets is reported. The global fit of all data gives sigma=3.4+/-0.2 mb, which is significantly smaller than previous estimates. A similar value, sigma=3.5+/-0.2 mb, is obtained when the nDS nuclear parton densities are included in the analysis, although we emphasize that the present uncertainties on gluon (anti)shadowing do not allow for a precise determination of sigma. Finally, no significant energy dependence of the J/psi-N interaction is observed, unless strong nuclear modifications of the parton densities are assumed.Comment: 25 pages, 5 figure

2018 American Heart Association Focused Update on Pediatric Advanced Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

This 2018 American Heart Association focused update on pediatric advanced life support guidelines for cardiopulmonary resuscitation and emergency cardiovascular care follows the 2018 evidence review performed by the Pediatric Task Force of the International Liaison Committee on Resuscitation. It aligns with the International Liaison Committee on Resuscitation's continuous evidence review process, and updates are published when the group completes a literature review based on new published evidence. This update provides the evidence review and treatment recommendation for antiarrhythmic drug therapy in pediatric shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. As was the case in the pediatric advanced life support section of the "2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care," only 1 pediatric study was identified. This study reported a statistically significant improvement in return of spontaneous circulation when lidocaine administration was compared with amiodarone for pediatric ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. However, no difference in survival to hospital discharge was observed among patients who received amiodarone, lidocaine, or no antiarrhythmic medication. The writing group reaffirmed the 2015 pediatric advanced life support guideline recommendation that either lidocaine or amiodarone may be used to treat pediatric patients with shock-refractory ventricular fibrillation or pulseless ventricular tachycardia

2019 American Heart Association focused update on pediatric advanced life support: An update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care

This 2019 focused update to the American Heart Association pediatric advanced life support guidelines follows the 2018 and 2019 systematic reviews performed by the Pediatric Life Support Task Force of the International Liaison Committee on Resuscitation. It aligns with the continuous evidence review process of the International Liaison Committee on Resuscitation, with updates published when the International Liaison Committee on Resuscitation completes a literature review based on new published evidence. This update provides the evidence review and treatment recommendations for advanced airway management in pediatric cardiac arrest, extracorporeal cardiopulmonary resuscitation in pediatric cardiac arrest, and pediatric targeted temperature management during post–cardiac arrest care. The writing group analyzed the systematic reviews and the original research published for each of these topics. For airway management, the writing group concluded that it is reasonable to continue bag-mask ventilation (versus attempting an advanced airway such as endotracheal intubation) in patients with out-of-hospital cardiac arrest. When extracorporeal membrane oxygenation protocols and teams are readily available, extracorporeal cardiopulmonary resuscitation should be considered for patients with cardiac diagnoses and in-hospital cardiac arrest. Finally, it is reasonable to use targeted temperature management of 32°C to 34°C followed by 36°C to 37.5°C, or to use targeted temperature management of 36°C to 37.5°C, for pediatric patients who remain comatose after resuscitation from out-of-hospital cardiac arrest or in-hospital cardiac arrest

Multimessenger astronomy with the Einstein Telescope

Gravitational waves (GWs) are expected to play a crucial role in the development of multimessenger astrophysics. The combination of GW observations with other astrophysical triggers, such as from gamma-ray and X-ray satellites, optical/radio telescopes, and neutrino detectors allows us to decipher science that would otherwise be inaccessible. In this paper, we provide a broad review from the multimessenger perspective of the science reach offered by the third generation interferometric GW detectors and by the Einstein Telescope (ET) in particular. We focus on cosmic transients, and base our estimates on the results obtained by ET's predecessors GEO, LIGO, and Virgo.Comment: 26 pages. 3 figures. Special issue of GRG on the Einstein Telescope. Minor corrections include

Choice of tracers for the evaluation of spray deposits

Tracer substances, used to evaluate spraying effectiveness, ordinarily modify the surface tension of aqueous solutions. This study aimed to establish a method of using tracers to evaluate distribution and amount of spray deposits, adjusted to the surface tension of the spraying solution. The following products were tested: 0.15% Brilliant Blue, 0.15% Saturn Yellow in 0.015% Vixilperse lignosulfonate, and 0.005% sodium fluorescein, and mixtures of Brilliant Blue plus Saturn Yellow and Brilliant Blue plus sodium fluorescein at the same concentrations. Solutions were deposited on citrus leaves and stability was determined by measuring fluorescence and optical density of solutions without drying, dried in the dark and exposed to sunlight for 2, 4 and 8 h. These values were compared to those obtained directly in water. The static surface tension of the tracer solution was determined by weighing droplets formed during a period of 20 to 40 seconds. The Brilliant Blue and Saturn Yellow mixture at 0.15% was stable under all conditions tested. It was not absorbed by the leaves and maintained the same surface tension as that of water, thus permitting concentration adjustment to the same levels used for agrochemical products, and allowing the development of a qualitative method based on visual evaluation of the distribution of the pigment under ultraviolet light and of a quantitative method based on the determination of the amount of the dye deposited in the same solution. Spray deposition could be evaluated at different surface tensions of the spraying solution, simulating the effect of agrochemical formulations

Planck 2015 results. XXVII. The Second Planck Catalogue of Sunyaev-Zeldovich Sources

We present the all-sky Planck catalogue of Sunyaev-Zeldovich (SZ) sources detected from the 29 month full-mission data. The catalogue (PSZ2) is the largest SZ-selected sample of galaxy clusters yet produced and the deepest all-sky catalogue of galaxy clusters. It contains 1653 detections, of which 1203 are confirmed clusters with identified counterparts in external data-sets, and is the first SZ-selected cluster survey containing > $10^3$ confirmed clusters. We present a detailed analysis of the survey selection function in terms of its completeness and statistical reliability, placing a lower limit of 83% on the purity. Using simulations, we find that the Y5R500 estimates are robust to pressure-profile variation and beam systematics, but accurate conversion to Y500 requires. the use of prior information on the cluster extent. We describe the multi-wavelength search for counterparts in ancillary data, which makes use of radio, microwave, infra-red, optical and X-ray data-sets, and which places emphasis on the robustness of the counterpart match. We discuss the physical properties of the new sample and identify a population of low-redshift X-ray under- luminous clusters revealed by SZ selection. These objects appear in optical and SZ surveys with consistent properties for their mass, but are almost absent from ROSAT X-ray selected samples