Objective
Neutrophil extracellular traps (NETs) have been shown to promote thrombus formation. Little is known about the exact composition of thrombi that cause ischemic stroke. In particular, no ...information is yet available on the presence of NETs in cerebral occlusions. Such information is, however, essential to improve current thrombolytic therapy with tissue plasminogen activator (t‐PA). This study aimed at investigating the presence of neutrophils and more specifically NETs in ischemic stroke thrombi.
Methods
Sixty‐eight thrombi retrieved from ischemic stroke patients undergoing endovascular treatment were characterized by immunostaining using neutrophil markers (CD66b and neutrophil elastase) and NET markers (citrullinated histone H3 H3Cit and extracellular DNA). Neutrophils and NETs were quantified. In addition, extracellular DNA was targeted by performing ex vivo lysis of retrieved thrombi with DNase 1 and t‐PA.
Results
Neutrophils were detected extensively throughout all thrombi. H3Cit, a hallmark of NETs, was observed in almost all thrombi. H3Cit‐positive area varied up to 13.45% of total thrombus area. Colocalization of H3Cit with extracellular DNA released from neutrophils confirmed the specific presence of NETs. H3Cit was more abundant in thrombi of cardioembolic origin compared to other etiologies. Older thrombi contained significantly more neutrophils and H3Cit compared to fresh thrombi. Interestingly, ex vivo lysis of patient thrombi was more successful when adding DNase 1 to standard t‐PA.
Interpretation
Neutrophils and NETs form important constituents of cerebral thrombi. Targeting of NETs with DNase 1 might have prothrombolytic potential in treatment of acute ischemic stroke. Ann Neurol 2017;82:223–232
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We compare the observed size distribution of circumstellar discs in the Orion Trapezium cluster with the results of N-body simulations in which we incorporated an heuristic prescription for the ...evolution of these discs. In our simulations, the sizes of stellar discs are affected by close encounters with other stars (with discs). We find that the observed distribution of disc sizes in the Orion Trapezium cluster is excellently reproduced by truncation due to dynamical encounters alone. The observed distribution appears to be a sensitive measure of the past dynamical history of the cluster, and therewith on the conditions of the cluster at birth. The best comparison between the observed disc-size distribution and the simulated distribution is realized with a cluster of N = 2500 ± 500 stars with a half-mass radius of about 0.5 pc in virial equilibrium (with a virial ratio of Q = 0.5, or somewhat colder Q ≃ 0.3), and with a density structure according to a fractal dimension of F ≃ 1.6. Simulations with these parameters reproduce the observed distribution of circumstellar discs in about 0.2–0.5 Myr. We conclude that the distribution of disk sizes in the Orion Trapezium cluster is the result of dynamical interactions in the early evolution of the cluster.
We present a method for studying the secular gravitational dynamics of hierarchical multiple systems consisting of nested binaries, which is valid for an arbitrary number of bodies and arbitrary ...hierarchical structure. We derive the Hamiltonian of the system and expand it in terms of the – assumed to be – small ratios xi
of binary separations. At the lowest non-trivial expansion order (quadrupole order, second order in xi
), the Hamiltonian consists of terms which, individually, depend on binary pairs. At higher orders, in addition to terms depending on binary pairs, we also find terms which, individually, depend on more than two binaries. In general, at order n in xi
, individual terms depend on at most n − 1 binaries. We explicitly derive the Hamiltonian including all terms up and including third order in xi
(octupole order), and including the binary pairwise terms up and including fifth order in xi
. These terms are orbit averaged, and we present a new algorithm for efficiently solving the equations of motion. This algorithm is highly suitable for studying the secular evolution of hierarchical systems with complex hierarchies, making long-term integrations of such systems feasible. We show that accurate results are obtained for multiplanet systems with semimajor axis ratios as large as ≈0.4, provided that high-order terms are included. In addition to multiplanet systems with a single star, we apply our results to multistar systems with multiple planets.
Eukaryotic cells are large enough to detect signals and then orient to them by differentiating the signal strength across the length and breadth of the cell. Amoebae, fibroblasts, neutrophils and ...growth cones all behave in this way. Little is known however about cell motion and searching behavior in the absence of a signal. Is individual cell motion best characterized as a random walk? Do individual cells have a search strategy when they are beyond the range of the signal they would otherwise move toward? Here we ask if single, isolated, Dictyostelium and Polysphondylium amoebae bias their motion in the absence of external cues.
We placed single well-isolated Dictyostelium and Polysphondylium cells on a nutrient-free agar surface and followed them at 10 sec intervals for approximately 10 hr, then analyzed their motion with respect to velocity, turning angle, persistence length, and persistence time, comparing the results to the expectation for a variety of different types of random motion.
We find that amoeboid behavior is well described by a special kind of random motion: Amoebae show a long persistence time ( approximately 10 min) beyond which they start to lose their direction; they move forward in a zig-zag manner; and they make turns every 1-2 min on average. They bias their motion by remembering the last turn and turning away from it. Interpreting the motion as consisting of runs and turns, the duration of a run and the amplitude of a turn are both found to be exponentially distributed. We show that this behavior greatly improves their chances of finding a target relative to performing a random walk. We believe that other eukaryotic cells may employ a strategy similar to Dictyostelium when seeking conditions or signal sources not yet within range of their detection system.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Motor primitive analyses can capture kinematic and muscle level organization of movement across reflex, locomotor and novel skilled tasks. • Kinematic structure and a compositional ...system of motor primitives are found across many species ranging from octopus through frog to man. • Kinetic/muscle synergy types of motor primitives are found in limb use in all tetrapod vertebrates examined. • Representation of ethologically important motor primitives has been reported for reaching and grasping tasks in primates. • Data supporting collections of motor primitives embedded at a low level in spinal cord now derive from a range of methods and species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Compared to individual hot days/nights, compound hot extremes that combine daytime and nighttime heat are more impactful. However, past and future changes in compound hot extremes as well as their ...underlying drivers and societal impacts remain poorly understood. Here we show that during 1960-2012, significant increases in Northern Hemisphere average frequency (~1.03 days decade
) and intensity (~0.28 °C decade
) of summertime compound hot extremes arise primarily from summer-mean warming. The forcing of rising greenhouse gases (GHGs) is robustly detected and largely accounts for observed trends. Observationally-constrained projections suggest an approximate eightfold increase in hemispheric-average frequency and a threefold growth in intensity of summertime compound hot extremes by 2100 (relative to 2012), given uncurbed GHG emissions. Accordingly, end-of-century population exposure to compound hot extremes is projected to be four to eight times the 2010s level, dependent on demographic and climate scenarios.
Approximately 0.2 ± 0.2 of white dwarfs (WDs) show signs of pollution by metals, which is likely due to the accretion of tidally disrupted planetary material. Models invoking planet–planet ...interactions after WD formation generally cannot explain pollution at cooling times of several Gyr. We consider a scenario in which a planet is perturbed by Lidov–Kozai oscillations induced by a binary companion and exacerbated by stellar mass-loss, explaining pollution at long cooling times. Our computed accretion rates are consistent with observations assuming planetary masses between ∼0.01 and 1 M
Mars, although non-gravitational effects may already be important for masses ≲0.3 M
Mars. The fraction of polluted WDs in our simulations, ∼0.05, is consistent with observations of WDs with intermediate cooling times between ∼0.1 and 1 Gyr. For cooling times ≲0.1 Gyr and ≳1 Gyr, our scenario cannot explain the high observed pollution fractions of up to 0.7. Nevertheless, our results motivate searches for companions around polluted WDs.
Phosphorus (P) is an essential element for all living organisms and cannot be replaced. Municipal sewage sludge is a carrier of phosphorus, but also contains organic pollutants and heavy metals. A ...two-step thermal treatment is suggested, including mono-incineration of sewage sludge and subsequent thermochemical treatment of the ashes. Organic pollutants are completely destroyed by mono-incineration. The resulting sewage sludge ashes contain P, but also heavy metals. P in the ashes exhibits low bioavailability, a disadvantage in farming. Therefore, in a second thermochemical step, P is transferred into mineral phases available for plants, and heavy metals are removed as well. The thermochemical treatment was investigated in a laboratory-scale rotary furnace by treating seven different sewage sludge ashes under systematic variation of operational parameters. Heavy metal removal and the increase of the P-bioavailability were the focus of the investigation. The present experimental study shows that these objectives have been achieved with the proposed process. The P-bioavailability was significantly increased due to the formation of new mineral phases such as chlorapatite, farringtonite and stanfieldite during thermochemical treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Vaccinations mandates have long been common as a requirement to school entry.•Mandates may serve as a crucial policy tool to reign in COVID-19.•Americans large favor these mandates, on average, in ...general.•Support is lower for COVID-19-related mandates.•Partisanship plays an important role in predicting opposition.
With effective and safe COVID-19 vaccines beginning to be distributed across the United States, questions about who should receive the vaccine first have been the focus of public discussions. Yet, over the long-term, questions about the order of distribution will be displaced by questions about how to achieve high levels of vaccination rates. Historically, absent incentives or mandates, Americans have shown ambivalence, if not general antipathy, towards vaccinations, and vaccination rates have generally been low for many vaccines. There is evidence that vaccination requirements across educational settings are an effective policy instrument to increase vaccination rates. We administered a large national survey to assess American’s attitudes towards vaccination requirements across three educational settings (daycare, K-12 schools, and universities) in general and for COVID-19 specifically. Partisanship, gender, race, rurality, and perceptions about the appropriate role schools should play in providing health services are substantive predictors of public opinion. While Americans generally support vaccination mandates across all three settings for both types of requirements, support is consistently and significantly lower for COVID19 requirements. The effect of partisanship is accentuated for COVID-19 requirements as compared to general requirements. Drop off in support between general and COVID-19 specific requirements are driven by partisanship, gender, political knowledge, rurality, and having children in the household. Nonetheless, mandates are supported by a majority of Americans. Assessing Americans’ opinions of vaccination requirements in educational settings offers an important opportunity to explore the potential of mandates as policy instrument in the government’s arsenal against COVID-19 and guide public policy on the issues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We study the UV divergences in the action of the 'Wheeler-de Witt patch' in asymptotically AdS spacetimes, which has been conjectured to be dual to the computational complexity of the state of the ...dual field theory on a spatial slice of the boundary. We show that including a surface term in the action on the null boundaries which ensures invariance under coordinate transformations has the additional virtue of removing a stronger than expected divergence, making the leading divergence proportional to the proper volume of the boundary spatial slice. We compare the divergences in the action to divergences in the volume of a maximal spatial slice in the bulk, finding that the qualitative structure is the same, but subleading divergences have different relative coefficients in the two cases.
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