Similar to adults with posttraumatic stress disorder, children with early life adversity show bias in memory for negative emotional stimuli. However, it is not well understood how childhood adversity impacts mechanisms underlying emotional memory. N = 56 children (8–14 years, 48% female) reported on adverse experiences including potentially traumatic events and underwent fMRI while attending to emotionally pleasant, neutral, or negative images. Post-scan, participants completed a cued recall test to assess memory for these images. Emotional difference-in-memory (DM) scores were computed by subtracting negative or positive from neutral recall performance. All children showed enhancing effects of emotion on recall, with no effect of trauma load. However, children with less trauma showed a larger emotional DM for both positive and negative stimuli when amygdala or anterior hippocampal activity was higher. In contrast, highly trauma-exposed children demonstrated a lower emotional DM with greater amygdala or hippocampal activity. This suggested that alternative neural mechanisms might support emotional enhancement of encoding in children with greater trauma load. Whole-brain analyses revealed that right fusiform activity during encoding positively correlated with both trauma load and successful later recall of positive images. Therefore, highly trauma-exposed children may use alternative, potentially adaptive neural pathways via the ventral visual stream to encode positive emotional events.

Magnetic reconnection is an important process in astrophysical environments, as it reconfigures magnetic field topology and converts magnetic energy into thermal and kinetic energy. In extreme astrophysical systems, such as black hole coronae and pulsar magnetospheres, radiative cooling modifies the energy partition by radiating away internal energy, which can lead to the radiative collapse of the reconnection layer. In this paper, we perform two- and three-dimensional simulations to model the MARZ (Magnetic Reconnection on Z) experiments, which are designed to access cooling rates in the laboratory necessary to investigate reconnection in a previously unexplored radiatively cooled regime. These simulations are performed in GORGON, an Eulerian two-temperature resistive magnetohydrodynamic code, which models the experimental geometry comprising two exploding wire arrays driven by 20 MA of current on the Z machine (Sandia National Laboratories). Radiative losses are implemented using non-local thermodynamic equilibrium tables computed using the atomic code Spk, and we probe the effects of radiation transport by implementing both a local radiation loss model and $P_{1/3}$ multi-group radiation transport. The load produces highly collisional, super-Alfvénic (Alfvén Mach number $M_A \approx 1.5$), supersonic (Sonic Mach number $M_S \approx 4-5$) strongly driven plasma flows which generate an elongated reconnection layer (Aspect Ratio $L/\delta \approx 100$, Lundquist number $S_L \approx 400$). The reconnection layer undergoes radiative collapse when the radiative losses exceed the rates of ohmic and compressional heating (cooling rate/hydrodynamic transit rate = $\tau _{\text {cool}}^{-1}/\tau _{H}^{-1}\approx 100$); this generates a cold strongly compressed current sheet, leading to an accelerated reconnection rate, consistent with theoretical predictions. Finally, the current sheet is also unstable to the plasmoid instability, but the magnetic islands are extinguished by strong radiative cooling before ejection from the layer.

Flow physics vary in different regimes across the full Mach number range, with our knowledge being particularly poor about the hypersonic regime. An Eulerian realization of the particles on demand method, a kinetic model formulated in the comoving reference frame, is proposed to simulate hypersonic compressible flows. The present model allows for flux evaluation in different reference frames, in this case rescaled and shifted by local macroscopic quantities, i.e. fluid speed and temperature. The resulting system of coupled hyperbolic equations is discretized in physical space with a finite volume scheme ensuring exact conservation properties. Regularization via Grad expansion is introduced to implement distribution function and flux transformation between different reference frames. It is shown that the proposed method possesses Galilean invariance at a Mach number up to $100$. Different benchmarks including both inviscid and viscous flows are reproduced with the Mach number up to $198$ and pressure ratio up to $10^5$. Finally, the new model is demonstrated to be capable of simulating hypersonic reactive flows, including one-dimensional and two-dimensional detonations. The developed methodology opens up possibilities for the simulation of the full range of compressible flows, without or with chemical reactions, from the subsonic to hypersonic regimes, leading to enhanced understanding of flow behaviours across the full Mach number range.

We report on the development of an ultrafast optical parametric amplifier front-end for the Petawatt High Energy Laser for heavy Ion eXperiments (PHELIX) and the Petawatt ENergy-Efficient Laser for Optical Plasma Experiments (PEnELOPE) facilities. This front-end delivers broadband and stable amplification up to 1 mJ per pulse while maintaining a high beam quality. Its implementation at PHELIX allowed one to bypass the front-end amplifier, which is known to be a source of pre-pulses. With the bypass, an amplified spontaneous emission contrast of $4.9\times {10}^{-13}$ and a pre-pulse contrast of $6.2\times {10}^{-11}$ could be realized. Due to its high stability, high beam quality and its versatile pump amplifier, the system offers an alternative for high-gain regenerative amplifiers in the front-end of various laser systems.

Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.

OBJECTIVES/GOALS: To characterize the oncogenic potential of HNSCC cell lines harboring 17 non-canonical PIK3CA mutations. METHODS/STUDY POPULATION: Non-canonical PIK3CA mutant constructs generated via site-directed mutagenesis are subcloned into doxycycline-inducible vector pLVX-Puro. Serum-dependent HNSCC cell line (PCI-52-SD1) is then stably transfected with vectors and undergo doxycycline-induction. Cell survival is determined by depriving cells of fetal bovine serum for 72 hours and quantifying remaining cells with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell proliferation and migration is evaluated with colony formation assays and transwell assays respectively. RESULTS/ANTICIPATED RESULTS: To date, the survival behavior of eight non-canonical mutants was assessed. Three mutants – Q75E, V71I, and E970K – exhibited 18.7-26.7% greater survival rate relative to cells transfected with wild-type. Five mutants – R519G, Y606C, W328S, C905S, and M1040I – demonstrated survival rates that differed only by −4.3% to +6.6% relative to wild-type. We hypothesize the three activating mutants that exhibited increased survival will also demonstrate increased cell proliferation and migratory behavior whereas the three neutral mutants will not differ from control. DISCUSSION/SIGNIFICANCE OF IMPACT: Ongoing HNSCC PI3K inhibitor trials could be more effective if all PIK3CA hyperactivation mutations are known. Identifying non-canonical mutation effects could result in greater efficacy if drugs are restricted only to those with activating mutations. CONFLICT OF INTEREST DESCRIPTION: JRG and DEJ are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics, Inc. STAT3 Therapeutics, Inc. holds an interest in a cyclic STAT3 decoy oligonucleotide. The remaining authors declare no conflicts.

Flexibility is one of the important mechanical performance parameters of stent. The flexibility of tapered stents, especially self-expanding tapered stents, remains unknown. In this study, we developed a new selfexpanding tapered stent for tapered arteries and performed a numerical investigation of stent flexibility by using finite element method. The effect of stent design parameters, including taper and link space width, on stent flexibility was studied. The flexibility of the proposed stent was also compared with that of traditional cylindrical stents. Results show that the tapered stent is more flexible than the traditional cylindrical stent. Furthermore, the flexibility of the tapered stent increases with increasing stent taper and stent link space width. The increase in the stent link space width can contribute to the reduction in the peak stress. Therefore, tapered stents with high link space width will improve the stent flexibility. This work provides useful information for improvement of stent design and clinical selection.