Three-body interactions with cold polar molecules

We show that polar molecules driven by microwave fields give naturally rise to strong three-body interactions, while the two-particle interaction can be independently controlled and even switched off. The derivation of these effective interaction potentials is based on a microscopic understanding of the underlying molecular physics, and follows from a well controlled and systematic expansion into many-body interaction terms. For molecules trapped in an optical lattice, we show that these interaction potentials give rise to Hubbard models with strong nearest-neighbor two-body and three-body interaction. As an illustration, we study the one-dimensional Bose-Hubbard model with dominant three-body interaction and derive its phase diagram.Comment: 8 pages, 4 figure

Generalized nonreciprocity in an optomechanical circuit via synthetic magnetism and reservoir engineering

Synthetic magnetism has been used to control charge neutral excitations for applications ranging from classical beam steering to quantum simulation. In optomechanics, radiation-pressure-induced parametric coupling between optical (photon) and mechanical (phonon) excitations may be used to break time-reversal symmetry, providing the prerequisite for synthetic magnetism. Here we design and fabricate a silicon optomechanical circuit with both optical and mechanical connectivity between two optomechanical cavities. Driving the two cavities with phase-correlated laser light results in a synthetic magnetic flux, which in combination with dissipative coupling to the mechanical bath, leads to nonreciprocal transport of photons with 35dB of isolation. Additionally, optical pumping with blue-detuned light manifests as a particle non-conserving interaction between photons and phonons, resulting in directional optical amplification of 12dB in the isolator through direction. These results indicate the feasibility of utilizing optomechanical circuits to create a more general class of nonreciprocal optical devices, and further, to enable novel topological phases for both light and sound on a microchip.Comment: 18 pages, 8 figures, 4 appendice

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study.

BACKGROUND: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D. METHODS: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography-mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis. RESULTS: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)]. CONCLUSIONS: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.The InterAct project was funded by the European Union Framework 6 (LSHM_CT_2006_037197). Biomarker measurements for vitamin D metabolites were funded jointly by the InterAct project, the MRC Cambridge Initiative (RG71466, SJAH/004) and the EPIC-CVD project. EPIC-CVD has been supported by the European Union Framework 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the UK Medical Research Council (G0800270 and MR/L003120/1), the British Heart Foundation (SP/09/002 and RG/08/014 and RG13/13/30194) and the UK National Institute of Health Research. In addition, InterAct investigators acknowledge funding from the following agencies: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014), Regional Government of Asturias and Regional Governments of Basque Country. Dr. Ivonne Sluijs is supported by the Junior Dr. Dekker grant (2015T019) from the Dutch Heart Foundation. Dr. Guy Fagherazzi is supported by the French Research Agency (Agence Nationale de la Recherche) via an “Investissement d’Avenir” grant (investment for the future grant, ANR-10-COHO-0006) and by the IDEX Paris Saclay Nutriperso Project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701708

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. RESULTS: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. CONCLUSIONS/INTERPRETATION: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions

Defective Lamin A-Rb Signaling in Hutchinson-Gilford Progeria Syndrome and Reversal by Farnesyltransferase Inhibition

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging

Predicted Functions of MdmX in Fine-Tuning the Response of p53 to DNA Damage

Tumor suppressor protein p53 is regulated by two structurally homologous proteins, Mdm2 and MdmX. In contrast to Mdm2, MdmX lacks ubiquitin ligase activity. Although the essential interactions of MdmX are known, it is not clear how they function to regulate p53. The regulation of tumor suppressor p53 by Mdm2 and MdmX in response to DNA damage was investigated by mathematical modeling of a simplified network. The simplified network model was derived from a detailed molecular interaction map (MIM) that exhibited four coherent DNA damage response pathways. The results suggest that MdmX may amplify or stabilize DNA damage-induced p53 responses via non-enzymatic interactions. Transient effects of MdmX are mediated by reservoirs of p53∶MdmX and Mdm2∶MdmX heterodimers, with MdmX buffering the concentrations of p53 and/or Mdm2. A survey of kinetic parameter space disclosed regions of switch-like behavior stemming from such reservoir-based transients. During an early response to DNA damage, MdmX positively or negatively regulated p53 activity, depending on the level of Mdm2; this led to amplification of p53 activity and switch-like response. During a late response to DNA damage, MdmX could dampen oscillations of p53 activity. A possible role of MdmX may be to dampen such oscillations that otherwise could produce erratic cell behavior. Our study suggests how MdmX may participate in the response of p53 to DNA damage either by increasing dependency of p53 on Mdm2 or by dampening oscillations of p53 activity and presents a model for experimental investigation