Gradio: Project proposal for satellite gradiometry

A gradiometric approach, rather than the more complicated satellite to satellite tracking, is proposed for studying anomalies in the gravitational fields of the Earth and, possibly, other telluric bodies. The first analyses of a gradiometer based on four of ONERA's CACTUS or SUPERCACTUS accelerometers are summarized. it is shown that the obstacles to achieving the required accuracy are not insuperable. The device will be carried in a 1000 kg lens shaped satellite in a heliosynchronous orbit 200 to 300 km in altitude. The first launching is planned for the end of 1987

GENETICS AND DEMOGRAPHY OF KELP GULLS IN PATAGONIA

The Kelp Gull (Larus dominicanus), a common seabird in coastal Patagonia, has recently increased in overall abundance and distribution, creating some concerns for the protection and conservation of other native, threatened species. We combined genetic and demographic data of four large Kelp Gull colonies distributed along 1800 km of the northern Patagonian coast of Argentina to further understand patterns of population growth and migration of the species. DNA analysis of variable intron sequences of two separate genes (myelin proteolipid protein, β-fibrinogen) revealed similar intra-colony levels of DNA sequence diversity. Pairwise FST comparisons revealed significant differentiation of the northernmost colony, Islote La Pastosa, from the two southern colonies, Punta Tombo and Isla Vernaci Sudoeste (p < 0.05). Indirect estimates of gene flow suggest significant mixing among colonies (Nm > 6). Demographic estimates revealed that Islote La Pastosa showed an increase in the number of breeding individuals over time (λ = 1.075), representing an area of potential population expansion. This is consistent with previous studies that have suggested that the demographic connectivity among Kelp Gull colonies in Patagonia may follow a source-sink dynamics, where growth rates of growing colonies are fuelled by the immigration of individuals from nearby colonies. The observed pattern also reflects the overall expansion of the species in the Patagonian region. This study suggests that proper management strategies for the Kelp Gull should take into account the genetic and demographic dynamics of this species

Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio.

Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30-40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08-0.19] mmol/L, p < 0.001; vs. +0.04 [-0.05-0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04-0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04-0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR - rather than CBF - could be used as a diagnostic indication for systemic lactate supplementation following TBI

using provenance data and DNA

Re-examination of the historical range of the greater prairie chicke

Limit cycle induced by multiplicative noise in a system of coupled Brownian motors

We study a model consisting of $N$ nonlinear oscillators with {\em global periodic} coupling and {\em local multiplicative} and additive noises. The model was shown to undergo a nonequilibrium phase transition towards a broken-symmetry phase exhibiting noise-induced "ratchet" behavior. A previous study \cite{[7]} focused on the relationship between the character of thehysteresis loop, the number of ``homogeneous'' mean-field solutions and the shape of the stationary mean-field probability distribution function. Here we show --as suggested by the absence of stable solutions when the load force is beyond a critical value-- the existence of a limit cycle induced by both:multiplicative noise and {\em global periodic} coupling.Comment: Submitted to Phys. Rev. E, RevTex, 18 pgs, 5 figure

Enhancement of Stochastic Resonance in distributed systems due to a selective coupling

Recent massive numerical simulations have shown that the response of a "stochastic resonator" is enhanced as a consequence of spatial coupling. Similar results have been analytically obtained in a reaction-diffusion model, using "nonequilibrium potential" techniques. We now consider a field-dependent diffusivity and show that the "selectivity" of the coupling is more efficient for achieving stochastic-resonance enhancement than its overall value in the constant-diffusivity case.Comment: 10 pgs (RevTex), 4 figures, submitted to Phys.Rev.Let

Association of Early Norepinephrine Administration With 24-Hour Mortality Among Patients With Blunt Trauma and Hemorrhagic Shock.

Hemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged. To evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock. This retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of >10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022. Continuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines. The primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE. A total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from -4.6 (95% CI, -11.9 to 2.7) to 2.1 (95% CI, -2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from -1.3 (95% CI, -9.5 to 6.9) to 5.3 (95% CI, -2.1 to 12.8). The findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock

Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker