A hybrid approach for solving the gravitational N-body problem with Artificial Neural Networks

Simulating the evolution of the gravitational N-body problem becomes extremely computationally expensive as N increases since the problem complexity scales quadratically with the number of bodies. We study the use of Artificial Neural Networks (ANNs) to replace expensive parts of the integration of planetary systems. Neural networks that include physical knowledge have grown in popularity in the last few years, although few attempts have been made to use them to speed up the simulation of the motion of celestial bodies. We study the advantages and limitations of using Hamiltonian Neural Networks to replace computationally expensive parts of the numerical simulation. We compare the results of the numerical integration of a planetary system with asteroids with those obtained by a Hamiltonian Neural Network and a conventional Deep Neural Network, with special attention to understanding the challenges of this problem. Due to the non-linear nature of the gravitational equations of motion, errors in the integration propagate. To increase the robustness of a method that uses neural networks, we propose a hybrid integrator that evaluates the prediction of the network and replaces it with the numerical solution if considered inaccurate. Hamiltonian Neural Networks can make predictions that resemble the behavior of symplectic integrators but are challenging to train and in our case fail when the inputs differ ~7 orders of magnitude. In contrast, Deep Neural Networks are easy to train but fail to conserve energy, leading to fast divergence from the reference solution. The hybrid integrator designed to include the neural networks increases the reliability of the method and prevents large energy errors without increasing the computing cost significantly. For this problem, the use of neural networks results in faster simulations when the number of asteroids is >70.Comment: Accepted for publication in the Journal of Computational Physic

Multi-year school-based implementation and student outcomes of an evidence-based risk reduction intervention

Background Intervention effects observed in efficacy trials are rarely replicated when the interventions are broadly disseminated, underscoring the need for more information about factors influencing real-life implementation and program impact. Using data from the ongoing national implementation of an evidence-based HIV prevention program [Focus on Youth in The Caribbean (FOYC)] in The Bahamas, this study examines factors influencing teachers’ patterns of implementation, the impact of teachers’ initial implementation of FOYC, and subsequent delivery of the booster sessions on students’ outcomes. Methods Data were collected from the 80 government elementary and 34 middle schools between 2011 and 2014, involving 208 grade 6, 75 grade 7, and 58 grade 8 teachers and 4411 students initially in grade 6 and followed for 3 years. Student outcomes include HIV/AIDS knowledge, reproductive health skills, self-efficacy, and intention to use protection. Data from teachers includes implementation and modification of the curriculum, attitudes towards the prevention program, comfort level with the curriculum, and attendance at training workshops. Structural equation modeling and mixed-effect modeling analyses were applied to examine the impact of teachers’ implementation. Results Teachers’ attitudes towards and comfort with the intervention curriculum, and attendance at the curriculum training workshop had a direct effect on teachers’ patterns of implementation, which had a direct effect on student outcomes. Teachers’ attitudes had a direct positive effect on student outcomes. Teachers’ training in interactive teaching methods and longer duration as teachers were positively associated with teachers’ comfort with the curriculum. High-quality implementation in grade 6 was significantly related to student outcomes in grades 6 and 7 post-implementation. Level of implementation of the booster sessions in grades 7 and 8 were likewise significantly related to subsequent student outcomes in both grades. Conclusions High-quality initial implementation of a prevention program is significantly related to better program outcomes. Poor subsequent delivery of booster sessions can undermine the positive effects from the initial implementation while strong subsequent delivery of booster sessions can partially overcome poor initial implementation

Randomized Controlled Trial to Evaluate an Internet‐Based Self‐Management Program in Systemic Sclerosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148240/1/acr23595.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148240/2/acr23595_am.pd

Macrophage skewing by Phd2 haplodeficiency prevents ischemia by inducing arteriogenesis

The authors are thankful to Dr. P. Carmeliet for scientific discussion and support. VE-Cadherin:CreERT and PDGFRB:Cre transgenic mice were generated at the Cancer Research UK (London, UK) and kindly donated by Dr. R. Adams. The IKKβ floxed mice are a generous gift of Dr. M. Karin (UCSD, La Jolla, CA). The hydroxylase-deficient PHD2 construct was given by Dr. P. Ratcliffe (Oxford, UK).PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion. We show that Phd2 (also known as Egln1) haplodeficient (Phd2(+/-)) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2(+/-) mice was due to an expansion of tissue-resident, M2-like macrophages and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a pro-arteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2(+/-) macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders.This work was supported by grants from FWO (G.0726.10), Belgium, and from VIB. ED was granted by ARC, SC by FCT, RLO and VF by FWO, AH by DFG. CR was supported by COST action TD0901. MDP was supported by an ERC starting grant

Development of a biomechanical energy harvester

© 2009 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.

BACKGROUND: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. METHODS: Children weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. RESULTS: In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. CONCLUSIONS: Recommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation

Prolyl hydroxylase 2 inactivation enhances glycogen storage and promotes excessive neutrophilic responses.

Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival. These enhanced neutrophil responses were dependent upon increases in glycolytic flux and glycogen stores. Systemic administration of a HIF-prolyl hydroxylase inhibitor replicated the Phd2-deficient phenotype of delayed inflammation resolution. Together, these data identify Phd2 as the dominant HIF-hydroxylase in neutrophils under normoxic conditions and link intrinsic regulation of glycolysis and glycogen stores to the resolution of neutrophil-mediated inflammatory responses. These results demonstrate the therapeutic potential of targeting metabolic pathways in the treatment of inflammatory disease.This work was principally supported by a Wellcome Trust Senior Clinical Fellowship award (098516 to SRW), Medical Research Council (MRC) Clinical Training Fellowship awards (G0802255 to AART; MR/K023845/1 to RSD), an Academy of Medical Sciences (AMS) starter grant (to AART), a Wellcome Trust Senior Clinical Fellowship award (076945 to DHD), British Lung Foundation Fellowship (F05/7 to HMM), and a Engineering and Physical Sciences Research Council and Medical Research Council grant (EP/L016559/1, JAW). The MRC /University of Edinburgh Centre for Inflammation Research is supported by an MRC Centre Grant. The work of PC is supported by long-term structural funding-Methusalem funding from the Flemish Government. CJS thanks the Wellcome Trust and Cancer Research UK for support