The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of ...error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low
. Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.
Essentials Nitric oxide synthesis controls protein disulfide isomerase (PDI) function. Nitric oxide (NO) modulation of PDI controls endothelial thrombogenicity. S-nitrosylated PDI inhibits platelet ...function and thrombosis. Nitric oxide maintains vascular quiescence in part through inhibition of PDI. SUMMARY: Background Protein disulfide isomerase (PDI) plays an essential role in thrombus formation, and PDI inhibition is being evaluated clinically as a novel anticoagulant strategy. However, little is known about the regulation of PDI in the vasculature. Thiols within the catalytic motif of PDI are essential for its role in thrombosis. These same thiols bind nitric oxide (NO), which is a potent regulator of vessel function. To determine whether regulation of PDI represents a mechanism by which NO controls vascular quiescence, we evaluated the effect of NO on PDI function in endothelial cells and platelets, and thrombus formation in vivo. Aim To assess the effect of S-nitrosylation on the regulation of PDI and other thiol isomerases in the vasculature. Methods and results The role of endogenous NO in PDI activity was evaluated by incubating endothelium with an NO scavenger, which resulted in exposure of free thiols, increased thiol isomerase activity, and enhanced thrombin generation on the cell membrane. Conversely, exposure of endothelium to NO
carriers or elevation of endogenous NO levels by induction of NO synthesis resulted in S-nitrosylation of PDI and decreased surface thiol reductase activity. S-nitrosylation of platelet PDI inhibited its reductase activity, and S-nitrosylated PDI interfered with platelet aggregation, α-granule release, and thrombin generation on platelets. S-nitrosylated PDI also blocked laser-induced thrombus formation when infused into mice. S-nitrosylated ERp5 and ERp57 were found to have similar inhibitory activity. Conclusions These studies identify NO as a critical regulator of vascular PDI, and show that regulation of PDI function is an important mechanism by which NO maintains vascular quiescence.
BACKGROUNDTransgender and gender diverse people face significant stigma that can adversely affect their physical and mental health. However, the psychobiological link between lived experience and ...health has been underexplored in this population. We thus examine perceived distress, mental health, and physiological 'wear and tear' by indexing allostatic load (AL) and assess associations with a range of contextual and experiential factors from transmasculine people living in the United States. METHODSSixty-five people who identified as transgender men or along a transmasculine spectrum, living in Massachusetts, Vermont, and Rhode Island participated in The Transition Experience Study (age: M=31.8, range 18-55), which examines lived experience of social and medical transition and embodied gender minority/marginalization stress among a sample of transmasculine people. Based on in-depth in-person interview and survey data and inspired by an ecological systems model, we created indices representing (1) perceived progressive geopolitical climate; (2) socio-demographic advantage; (3) social support and resources; (4) gender minority and marginalization stressors; and (5) health behaviors. The Perceived Stress Scale and psychological symptoms (depression, anxiety, insomnia) were also assessed. AL indexed 10 neuroendocrine, immune, cardiovascular, and metabolic biomarkers. RESULTSRegressions revealed that perceived stress and psychological symptoms were negatively correlated with progressive geopolitical climate (respectively B=-1.47, p = 0.19; B=-.77, p < .001) and positively correlated with gender minority and marginalization stressors (respectively B=1.51, p < .001; B =.38, p = .005). AL was negatively associated with perceived progressive geopolitical climate (B=-.55, p = .007) and socio-demographic advantage (B=-3.2, p = .001). DISCUSSIONSThese findings underline the importance of assessing geopolitical context and indexing lived experiences and life domains along with biomarker sampling. Together, these enable the identification of psychobiological pathways to better nuance multi-level contributors to health and well-being and understand embodied inequalities. These analyses of embodied stigma inclusive of AL biomarkers thus provide a model to further research centering transgender people's health from youth through old age.
Tumors are largely classified by histologic appearance, yet morphologic features do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we ...labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features. We show that formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9. Moreover, when concomitantly expressed with oncogenic Kras, Sox9 accelerates formation of premalignant lesions. These results provide insight into the cellular origin of PDA and suggest that its precursors arise via induction of a duct-like state in acinar cells.
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► Preneoplastic lesions rarely arise from pancreatic ductal/centroacinar cells ► Acinar cells are the predominant cells of origin for pancreatic preneoplastic lesions ► Initiation of pancreatic cancer depends on acinar induction of the ductal gene Sox9 ► Sox9 synergizes with KrasG12D and injury in acinar-to-ductal cell reprogramming
Intense lasers interacting with dense targets accelerate relativistic electron beams, which transport part of the laser energy into the target depth. However, the overall laser-to-target energy ...coupling efficiency is impaired by the large divergence of the electron beam, intrinsic to the laser-plasma interaction. Here we demonstrate that an efficient guiding of MeV electrons with about 30 MA current in solid matter is obtained by imposing a laser-driven longitudinal magnetostatic field of 600 T. In the magnetized conditions the transported energy density and the peak background electron temperature at the 60-μm-thick target's rear surface rise by about a factor of five, as unfolded from benchmarked simulations. Such an improvement of energy-density flux through dense matter paves the ground for advances in laser-driven intense sources of energetic particles and radiation, driving matter to extreme temperatures, reaching states relevant for planetary or stellar science as yet inaccessible at the laboratory scale and achieving high-gain laser-driven thermonuclear fusion.
Nonhomologous end-joining (NHEJ) is a major DNA double-strand break repair pathway that is conserved in eukaryotes. In vertebrates, NHEJ further acquires end-processing capacities (e.g., hairpin ...opening) in addition to direct end-ligation. The catalytic subunit of DNA-PK (DNA-PKcs) is a vertebrate-specific NHEJ factor that can be autophosphorylated or transphosphorylated by ATM kinase. Using a mouse model expressing a kinase-dead (KD) DNA-PKcs protein, we show that ATM-mediated transphosphorylation of DNA-PKcs regulates end-processing at the level of Artemis recruitment, while strict autophosphorylation of DNA-PKcs is necessary to relieve the physical blockage on end-ligation imposed by the DNA-PKcs protein itself. Accordingly, DNA-PKcsKD/KD mice and cells show severe end-ligation defects and p53- and Ku-dependent embryonic lethality, but open hairpin-sealed ends normally in the presence of ATM kinase activity. Together, our findings identify DNA-PKcs as the molecular switch that coordinates end-processing and end-ligation at the DNA ends through differential phosphorylations.
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•DNA-PKcs protein inhibits direct end-ligation at the DNA ends•Intermolecular autophosphorylation of DNA-PKcs is required for end-ligation•DNA-PKcs protein, but not its kinase activity, is required for end-processing•ATM phosphorylates DNA-PKcs to recruit Artemis and promote end-processing
Differential phosphorylation of DNA-PKcs at DNA ends is the molecular switch between end-processing and end-ligation. ATM-mediated phosphorylation of DNA-PKcs is necessary for Artemis recruitment and end-processing, while intermolecular autophosphorylation of DNA-PKcs relieves the physical block on end-ligation imposed by the DNA-PKcs protein at DNA ends and is required for direct end-ligation.
We present an efficient approach to achieving arbitrary, high-fidelity control of a multilevel quantum system using optimal control techniques. As an demonstration, we implement a continuous, ...software-defined microwave pulse to realize a 0 ↔ 2 SWAP gate that achieves an average gate fidelity of 99.4%. We describe our procedure for extracting the system Hamiltonian, calibrating the quantum and classical hardware chain, and evaluating the gate fidelity. Our work represents an alternative, fully generalizable route towards achieving universal quantum control by leveraging optimal control techniques.
The roots of the obesity epidemic need to be traced back as early in life as possible in order to develop effective means for preventing obesity and its health consequences in the future. The aim of ...this paper is to examine a broad range of factors that may simultaneously contribute to childhood overweight in a population-based cohort of children followed from birth to 4.5 years, to determine which factors exert the most influence in early life.
The analyses were performed using data from the Quebec Longitudinal Study of Child Development 1998-2002 (QLSCD).
The study follows a representative sample (n=2103) of children born in 1998 in the Canadian province of Quebec.
Measured height and weight were available for 1550 children aged 4.5 years. At 4.5 years, BMI was analyzed using the US CDC sex- and age-specific growth charts. In order to study children at their highest weights at various ages, odds ratios were presented for high birth weight, weight-for-stature at or above the 95th percentile at 5 months, and BMI at or above the 95th percentile at 4.5 years. Monthly weight gain between birth and five months has been analyzed. Children were also evaluated by the Z-score obtained from the standardized weight divided by height. Factors potentially related to children's weight include sex, gestational age and birth rank, breastfeeding, mothers' smoking status during pregnancy, family type at child's birth, and family income before pregnancy and when the children were 5 months and 4.5 years old. Other parental factors such as height and overweight/obesity (based on BMI) and other maternal factors (age, education, immigrant status) were also part of the analysis.
Being in the highest quintiles of weight gain between birth and 5 months, as well as maternal smoking during pregnancy, almost double the odds of being overweight at 4.5 years. Parental overweight or obesity also increased the odds of being overweight at this age, as well as being raised in middle-income or in poor families. A greater proportion of children born to nonsmoking mothers with higher weights (more than 4000 g) were overweight at 4.5 years, the percentage being greatest for those in the highest weight-gain categories from birth to 5 months. The pattern was different for children born to smoking mothers. The greatest proportion of 4.5-year-old overweight children was seen for children born in the normal weight-range category (3000-4000 g) who were in the highest quintiles of weight gain from birth to 5 months, and for children with high birth weights (more than 4000 g) who were in the lowest quintiles of birth-to-5-months weight gain. Children who were overweight at 4.5 years and who had been born to smoking mothers started life with a birth weight around that for the population means, but they gained more weight in the first 5 months of life than did the children of nonsmoking mothers.
This study indicates that behavioral and social factors exert critical influences on the onset of childhood overweight in preschool years. From a population-health perspective, interventions aimed at preventing childhood obesity would do well to target smoking pregnant women, as well as nonsmoking pregnant women at risk for giving birth to high-birth-weight children, paying particular attention to rapid weight gain in the first months of life.
A strategic model of human resource management is proposed as a framework to support sustainable adaptation to the disruptive and dynamic challenges in the business context related to environmental ...sustainability. The implications of a whole‐systems ecological approach to the design and implementation of human resource systems are explored, and the literature on best HR practices to support environmental sustainability is summarized. Implications for practice and research are presented.
We perform calculations of the 3D finite-temperature homogeneous electron gas in the warm-dense regime (r(s) ≡ (3/4πn)(1/3)a(0)(-1) = 1.0-40.0 and Θ ≡ T/T(F) = 0.0625-8.0) using restricted ...path-integral Monte Carlo simulations. Precise energies, pair correlation functions, and structure factors are obtained. For all densities, we find a significant discrepancy between the ground state parametrized local density approximation and our results around T(F). These results can be used as a benchmark for developing finite-temperature density functionals, as well as input for orbital-free density function theory formulations.
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