Cerebral sinus venous thrombosis (CSVT) is an uncommon disease that is usually treated with anticoagulation (heparin, low-molecular heparin, or vitamin K-antagonists). We compared treatment with ...edoxaban, an oral factor Xa-antagonist, that has not been approved in patients with CSVT, with enoxaparin, a well-established therapy, in a rat model of CSVT. Fifty male Wistar rats were randomized into 5 groups (10 animals each) and subjected to aluminum chloride (AlCl3)-induced thrombosis of the superior sagittal sinus (SSS) or sham procedure. Animals with thrombosis of the SSS were treated with edoxaban, enoxaparin, or placebo. Diagnostic workup included neurological examination, MRI imaging, MR-flow measurements of the SSS, and immunohistochemical staining. Neurological examination revealed no differences between treatment groups. Seven days after initial thrombosis, flow in the SSS was lower in the active treatment group as compared to sham-operated animals (
p
< 0.05). Flow in the SSS in the active treatment groups (edoxaban 1 h prior to thrombosis: 0.16 cm/s ± 0.06 cm/s; edoxaban 6 h after thrombosis: 0.13 cm/s ± 0.05 cm/s; enoxaparin: 0.13 cm/s ± 0.04 cm/s; placebo: 0.07 cm/s ± 0.02 cm/s) was higher as compared to placebo (
p
< 0.05), but there were no differences between the active treatment groups (
p
> 0.05). Immunohistochemical staining showed no differences in the actively treated animals. Edoxaban proved to be similar to enoxaparin in a model of experimental AlCl
3
-induced CSVT.
Ignition is needed to make fusion energy a viable alternative energy source, but has yet to be achieved. A key step on the way to ignition is to have the energy generated through fusion reactions in ...an inertially confined fusion plasma exceed the amount of energy deposited into the deuterium-tritium fusion fuel and hotspot during the implosion process, resulting in a fuel gain greater than unity. Here we report the achievement of fusion fuel gains exceeding unity on the US National Ignition Facility using a 'high-foot' implosion method, which is a manipulation of the laser pulse shape in a way that reduces instability in the implosion. These experiments show an order-of-magnitude improvement in yield performance over past deuterium-tritium implosion experiments. We also see a significant contribution to the yield from α-particle self-heating and evidence for the 'bootstrapping' required to accelerate the deuterium-tritium fusion burn to eventually 'run away' and ignite.
Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic ...analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment.
This Letter reports on a series of high-adiabat implosions of cryogenic layered deuterium-tritium (DT) capsules indirectly driven by a "high-foot" laser drive pulse at the National Ignition Facility. ...High-foot implosions have high ablation velocities and large density gradient scale lengths and are more resistant to ablation-front Rayleigh-Taylor instability induced mixing of ablator material into the DT hot spot. Indeed, the observed hot spot mix in these implosions was low and the measured neutron yields were typically 50% (or higher) of the yields predicted by simulation. On one high performing shot (N130812), 1.7 MJ of laser energy at a peak power of 350 TW was used to obtain a peak hohlraum radiation temperature of ∼300 eV. The resulting experimental neutron yield was (2.4±0.05)×10(15) DT, the fuel ρR was (0.86±0.063) g/cm2, and the measured Tion was (4.2±0.16) keV, corresponding to 8 kJ of fusion yield, with ∼1/3 of the yield caused by self-heating of the fuel by α particles emitted in the initial reactions. The generalized Lawson criteria, an ignition metric, was 0.43 and the neutron yield was ∼70% of the value predicted by simulations that include α-particle self-heating.
The National Ignition Campaign's M. J. Edwards et al., Phys. Plasmas 20, 070501 (2013) point design implosion has achieved DT neutron yields of 7.5×10(14) neutrons, inferred stagnation pressures of ...103 Gbar, and inferred areal densities (ρR) of 0.90 g/cm2 (shot N111215), values that are lower than 1D expectations by factors of 10×, 3.3×, and 1.5×, respectively. In this Letter, we present the design basis for an inertial confinement fusion capsule using an alternate indirect-drive pulse shape that is less sensitive to issues that may be responsible for this lower than expected performance. This new implosion features a higher radiation temperature in the "foot" of the pulse, three-shock pulse shape resulting in an implosion that has less sensitivity to the predicted ionization state of carbon, modestly lower convergence ratio, and significantly lower ablation Rayleigh-Taylor instability growth than that of the NIC point design capsule. The trade-off with this new design is a higher fuel adiabat that limits both fuel compression and theoretical capsule yield. The purpose of designing this capsule is to recover a more ideal one-dimensional implosion that is in closer agreement to simulation predictions. Early experimental results support our assertions since as of this Letter, a high-foot implosion has obtained a record DT yield of 2.4×10(15) neutrons (within ∼70% of 1D simulation) with fuel ρR=0.84 g/cm2 and an estimated ∼1/3 of the yield coming from α-particle self-heating.
Although cellular prion protein (PrP(c)) has been suggested to have physiological roles in neurogenesis and angiogenesis, the pathophysiological relevance of both processes remain unknown. To ...elucidate the role of PrP(c) in post-ischemic brain remodeling, we herein exposed PrP(c) wild type (WT), PrP(c) knockout (PrP-/-) and PrP(c) overexpressing (PrP+/+) mice to focal cerebral ischemia followed by up to 28 days reperfusion. Improved neurological recovery and sustained neuroprotection lasting over the observation period of 4 weeks were observed in ischemic PrP+/+ mice compared with WT mice. This observation was associated with increased neurogenesis and angiogenesis, whereas increased neurological deficits and brain injury were noted in ischemic PrP-/- mice. Proteasome activity and oxidative stress were increased in ischemic brain tissue of PrP-/- mice. Pharmacological proteasome inhibition reversed the exacerbation of brain injury induced by PrP-/-, indicating that proteasome inhibition mediates the neuroprotective effects of PrP(c). Notably, reduced proteasome activity and oxidative stress in ischemic brain tissue of PrP+/+ mice were associated with an increased abundance of hypoxia-inducible factor 1α and PACAP-38, which are known stimulants of neural progenitor cell (NPC) migration and trafficking. To elucidate effects of PrP(c) on intracerebral NPC homing, we intravenously infused GFP(+) NPCs in ischemic WT, PrP-/- and PrP+/+ mice, showing that brain accumulation of GFP(+) NPCs was greatly reduced in PrP-/- mice, but increased in PrP+/+ animals. Our results suggest that PrP(c) induces post-ischemic long-term neuroprotection, neurogenesis and angiogenesis in the ischemic brain by inhibiting proteasome activity.
Encouraging results have been obtained using a strong first shock during the implosion of carbon-based ablator ignition capsules. These "high-foot" implosion results show that capsule performance ...deviates from 1D expectations as laser power and energy are increased. A possible cause of this deviation is the disruption of the hot spot by jets originating in the capsule fill tube. Nominally, a 10 μm outside diameter glass (SiO2) fill tube is used in these implosions. Simulations indicate that a thin coating of Au on this glass tube may lessen the hotspot disruption. These results and other mitigation strategies will be presented.
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