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Abstract Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients. Median follow up from T-DXd initiation was 13.9 months. The cumulative incidence of symptomatic radiation necrosis at 24 months per lesion was 2.1% and per patient 11%. The 12-month LC was 97%. HER2-low was associated with worse distant intracranial control (DIC) (adjusted HR 2.5, 95% CI 1.1–5.6, p = 0.03) and worse systemic progression free survival (PFS) (HR 4.1, 95% CI 1.6–10.7, p = 0.004). Concurrent SRS and T-DXd has excellent local control, without an increased risk of radiation necrosis. HER2-low disease is associated with worse systemic PFS and DIC with T-DXd compared to HER2+.

Semi-purified diets supplemented with either a high linoleate (n-6) (safflower) oil or a high alpha-linolenate (n-3) (perilla) oil were fed to mouse mothers and their offspring through 6 weeks of age. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets while no difference was found in phospholipid compositions or cholesterol/phospholipid ratios. In the elevated plus maze task, the total number of entries into the open- and enclosed-arms was smaller and the time spent in the dark enclosed arms tended to be longer in the perilla group than the safflower group. The time required to reach a safe platform in Morris's water maze test was less in the perilla group, but no significant difference was observed in the entries into the arms darkened with a movable cover in Y-maze dark-preference task. The safflower group was more sensitive to pentobarbital; the anesthesia onset time was less and the anesthetic time was longer than in the perilla group. Increased locomotion induced by scopolamine injection was less in the safflower group as compared with the perilla group. These results indicate that in mice the dietary alpha-linolenate/linoleate balance affects the n-3/n-6 ratio of brain phospholipid acyl chains and that this is accompanied by general behavioral changes as well as changes in sensitivities to drugs known to affect behavior.

Superconducting (SC) tokamak JT-60SA plays an essential role in fusion research and development by supporting and complementing the ITER project, providing directions to the DEMO design activity and fostering next generation scientists and engineers. Since the short circuit incident at the terminal joints of equilibrium field coil #1 during the integrated commissioning (IC) in March 2021, both EU and JA implementing agencies (IAs) have examined how to ensure safe operation of JT-60SA by mitigating the risk of possible discharge occurrence inside the cryostat. Based on the experience of the global Paschen tests, the IAs have established a strategy of risk mitigation measures, which is a combination of (i) reinforcement of insulation, (ii) avoiding unnecessary voltage application to the coil systems and (iii) immediate de-energization of the coils when deteriorated vacuum conditions are detected. Thanks to the considerable efforts of the Integrated Project Team members, the IC restarted in May 2023. After confirmation of the SC state of the coil systems (TF, EF and CS), the coil energization test and the plasma operation phase 1 (OP-1) started. The first plasma was successfully achieved on 23 October 2023 with a limited value of voltage and current applied to the coils. The plasma configuration control was also confirmed with low plasma current and low auxiliary heating power conditions. Based on the IO–F4E–QST collaboration, activities of JT-60SA have been shared with the IO and provided an important lesson for ITER assembly and commissioning, and will provide an outstanding contribution to fusion research at large. After OP-1, maintenance & enhancement phase 1 (M/E-1) starts from January 2024, in which in-vessel components are installed, and heating and diagnostic systems are extensively upgraded to allow a high power heating experiment planned in OP-2. In order to make the best use of JT-60SA, a newly organized JT-60SA experiment team will refine the research plan for the future high heating power operation phase.

This research numerically investigates the behavior of plasma flow in GAMMA 10/PDX. The impact of impurity gases seeding into the divertor region on the plasma parameters and the energy loss processes has been investigated numerically by using the multi-fluid code “LINDA”. The neutral particles are injected into the bulk hydrogen plasma and the upstream plasma parameters on the z-axis are ni=1.0×1019m−3, Ti=100eV,Te=30eV. A reduction in the plasma temperature has been observed with the increasing H neutral injection. The ionization and Charge-exchange (CX) power loss increase almost linearly with the increasing H neutral density, which induce a reduction in the plasma temperature. During H seeding, Ar and Ne are seeded simultaneously to observe the influence of Ar and Ne on the electron and ion energy loss mechanism. In this study, the fraction of impurity density to upstream plasma density (nz/ni) is used to be 10%. A comparison between Ar and Ne shows that Ar is effective on the electron cooling. The radiation power loss of Ar is found to be higher than that of Ne. The radiation cooling effect and CX loss significantly reduces the electron and ion temperature, respectively. A slight influence of Ar and Ne seeding on the ion energy loss terms has been observed. The electron energy loss terms increase significantly during impurity gas Ar and Ne seeding. These outcomes represent the impact of gas seeding for reducing the plasma energy on the divertor target plates. Keywords: GAMMA 10/PDX, Divertor simulation, Multi-fluid LINDA code, Plasma detachment

The transition of a detached to attached plasma experiment has been performed in GAMMA 10/PDX by applying an additional plasma heating pulse of electron cyclotron heating (ECH). In a plasma detachment experiment, a short pulse (25 ms) of ECH was applied at the east plug-cell to examine the effects of electron heating on the plasma parameters in the D-module. It was found that the ion flux increased significantly during ECH injection. In the ECH injection period, the ion flux increased with the increasing impurity injection, which indicates the impurity ion components are enhanced by ionization in the D-module due to the application of ECH. During ECH injection period, the increase of the ion flux near the corner of the target plate shows a clear dependence on the gas species. The 2D visible emission has been captured by the high-speed camera and a bright emission near the corner of the target has been observed. The spectroscopic measurement in the D-module shows that the impurity ion emission increases remarkably during ECH injection. These results indicate the detached plasma change to the attached state. Keywords: GAMMA 10/PDX, Divertor simulation experiment, Plasma detachment, Detached to attached transition

Nanostructures of diglycidyl ether of bisphenol-A epoxy/poly(methyl methacrylate)-b-poly(n-butyl acrylate)-b-poly(methyl methacrylate) (PMMA-b-PnBA-b-PMMA) triblock copolymer (BCP) blends were studied in relation to their mechanical properties. Three types of self-assembled nanostructures, such as spheres, random cylinders, and curved lamella, were controlled in phenol novolac-cured epoxy blends with a wide range of BCP content. Three types of nanostructures were observed using two-dimensional and three-dimensional transmission electron microscopy (TEM). The 3D-TEM, dynamic viscoelastic analyses, and theoretical model on the elastic modulus clarified that the spheres and the random cylinders, consisted of epoxy-immiscible PnBA phases, were discontinuously dispersed in the epoxy matrix. In contrast, the curved lamella formed co-continuous nanostructure, in which both the PnBA and epoxy phases formed continuous channels. The fracture toughness (critical strain energy release rate, GIC) and the flexural moduli of elasticity (E) of the cured blends were evaluated for various amounts of BCP content. The highest GIC was obtained from the random cylindrical nanostructured blends in the three types of nanostructures with the same PnBA content. The lowest E was obtained for the curved lamella with co-continuous nanostructures. The details of deformation and fracture events were observed using optical and electron microscopy, and the mechanical properties are discussed in relation to the nanostructures.

In the tandem mirror GAMMA 10/PDX, molecular activated recombination (MAR) leading to plasma detachment has been observed by additional hydrogen gas injection to the divertor simulation plasma (i.e. end loss plasma) which is exposed to the V-shaped target in the divertor simulation experimental module (D-module). The temperature near the corner of the V-shaped target decreased from ∼23eV to ∼2eV as the neutral pressure in the D-module increased. A clear density rollover was observed at ∼2Pa. A position of the density maximum moves to upstream of the plasma with increase in the neutral pressure and the density near the corner of the target decreases to detach the plasma from the target. After the occurrence of the density rollover, the Balmer β intensity decreases as with the density but the Balmer α intensity continues to increase, indicating the dissociative attachment process in MAR is more dominant than the ion conversion process although the rate coefficient of the former process is lower than that of the latter one, which is calculated by using a collisional radiative model. This would be caused by the MAR process related to triatomic hydrogen molecules which significantly contributed to the detachment process.

A frequency multiplied microwave interferometer, a Hα line emission measurement system, and a high speed camera system were installed on the Pilot-PSI device for low frequency fluctuation study in the detached plasma condition. The two dimensional Hα line emission and its fluctuation were monitored with a fast visible camera with Hα filter. The coherent low frequency fluctuations of frequency of approximately 13 kHz were measured by all measurement systems. The stronger fluctuation intensities were observed in the downstream of the ionization front region in the detached plasma condition. Moreover, we show the clear difference between the strong fluctuation regions of the electron line density and Hα line emission for the first time. This means that the fluctuations of Hα line emissions was caused by not only electrons but also by hydrogen ions.

Reaction processes of molecular activated recombination (MAR) have been investigated using end loss plasma in GAMMA 10/PDX. A tungsten V-shaped target in a divertor simulation experimental module (D-module) is exposed to the end loss plasma. The additional hydrogen gas is supplied into the D-module, leading to the plasma detachment by MAR. The vibrational temperature (Tvib) of H2(X1Σg+) increased up to ∼10,000 K with increasing the hydrogen gas pressure, and the Ha line intensity (IHa) continued to increase even though the electron density decreased after the electron density rollover. The increase in Tvib should be caused mainly by the increase in the number of vibrationally excited molecules which are produced by the molecular ion conversion process in MAR. The continuous increase in IHa is attributed to the dissociative attachment in MAR. When the hydrogen gas pressure was more than 12 Pa, Balmer emissions from highly excited atom suddenly increased and a population inversion with nH(n = 5) larger than nH (n = 4) was observed although Tvib became rather low (∼2,000 K). The formation of population inversion and increase in highly excited Balmer line intensity are considered to be caused by the reaction of mutual neutralization between molecular ion and negative ion, since the cross section of H(n = 5) production is the largest in the reaction. The negative ion should be produced by the resonant ionization process between H(2s), since the negative ion production by the dissociative attachment reaction cannot be expected due to low Tvib. Keywords: GAMMA 10/PDX, Divertor-simulation experiment, Plasma detachment, Molecular activated recombination, Molecular vibrational temperature, Population inversion

Stability of nanostructures of epoxy/acrylic triblock copolymer blends was studied.PMMA-b-PnBA-b-PMMA triblock copolymers (acrylic BCPs) having several compositions on the ratio of the block chains and the molecular weight were initially prepared and were blended with diglycidyl ether of bisphenol-A epoxy thermosets. The blends were cured using phenol novolac with tri phenyl phosphine (TPP) as the catalyst. Several nanostructures, such as spheres, cylinders, curved lamellae, were observed in the cured blends. The nanostructures were controlled by the molecular weight of the immiscible PnBA-block chain and the ratio of the PnBA in the blends. Moreover, the effect of the gel time to the nanostructures was examined by altering the trace amount of the TPP in the blends. The types of the nanostructures were almost kept irrespective of the gel time of the blends when the composition of the blends was maintained. This suggested the stability of the nanostructures of the epoxy/acrylic BCP blends made via the self-assembly mechanism, therefore a phase diagram of the cured blends was proposed.

The knowledge of motion dynamics during running activity is crucial to enhance the development of rehabilitation techniques and injury prevention programs. Recent studies investigated the interaction between joints, using several analysis techniques, as cross-correlation, sensitivity analysis, among others. However, the direction of the joints pairing is still not understood. This paper proposes a study of the influence direction pattern in healthy runners by using kinematic data together with partial directed coherence, a frequency approach of Granger causality. The analysis was divided into three anatomical planes, sagittal, frontal, and transverse, and using data from ankle, knee, hip, and trunk segments. Results indicate a predominance of proximal to distal influence during running, reflecting a centralized anatomic source of movements. These findings highlight the necessity of managing proximal joints movements, in addition to motor control and core (trunk and hip) strengthening training to lumbar spine, knee, and ankle injuries prevention and rehabilitation.

Organic peroxy (RO2) and hydroperoxy (HO2) radicals are key intermediates in the photochemical processes that generate ozone, secondary organic aerosol and reactive nitrogen reservoirs throughout the troposphere. In regions with ample biogenic hydrocarbons, the richness and complexity of peroxy radical chemistry presents a significant challenge to current-generation models, especially given the scarcity of measurements in such environments. We present peroxy radical observations acquired within a ponderosa pine forest during the summer 2010 Bio-hydro-atmosphere interactions of Energy, Aerosols, Carbon, H2O, Organics and Nitrogen – Rocky Mountain Organic Carbon Study (BEACHON-ROCS). Total peroxy radical mixing ratios reach as high as 180 pptv (parts per trillion by volume) and are among the highest yet recorded. Using the comprehensive measurement suite to constrain a near-explicit 0-D box model, we investigate the sources, sinks and distribution of peroxy radicals below the forest canopy. The base chemical mechanism underestimates total peroxy radicals by as much as a factor of 3. Since primary reaction partners for peroxy radicals are either measured (NO) or underpredicted (HO2 and RO2, i.e., self-reaction), missing sources are the most likely explanation for this result. A close comparison of model output with observations reveals at least two distinct source signatures. The first missing source, characterized by a sharp midday maximum and a strong dependence on solar radiation, is consistent with photolytic production of HO2. The diel profile of the second missing source peaks in the afternoon and suggests a process that generates RO2 independently of sun-driven photochemistry, such as ozonolysis of reactive hydrocarbons. The maximum magnitudes of these missing sources (~120 and 50 pptv min−1, respectively) are consistent with previous observations alluding to unexpectedly intense oxidation within forests. We conclude that a similar mechanism may underlie many such observations.

Biogenic emissions supply the largest fraction of non-methane volatile organic compounds (VOC) from the biosphere to the atmospheric boundary layer, and typically comprise a complex mixture of reactive terpenes. Due to this chemical complexity, achieving comprehensive measurements of biogenic VOC (BVOC) in air within a satisfactory time resolution is analytically challenging. To address this, we have developed a novel, fully automated Fast Gas Chromatography (Fast-GC) based technique to provide higher time resolution monitoring of monoterpenes (and selected other C9-C15 terpenes) during plant emission studies and in ambient air. To our knowledge, this is the first study to apply a Fast-GC based separation technique to achieve quantification of terpenes in ambient air. Three chromatography methods have been developed for atmospheric terpene analysis under different sampling scenarios. Each method facilitates chromatographic separation of selected BVOC within a significantly reduced analysis time compared to conventional GC methods, whilst maintaining the ability to quantify individual monoterpene structural isomers. Using this approach, the C9-C15 BVOC composition of single plant emissions may be characterised within a 14.5 min analysis time. Moreover, in-situ quantification of 12 monoterpenes in unpolluted ambient air may be achieved within an 11.7 min chromatographic separation time (increasing to 19.7 min when simultaneous quantification of multiple oxygenated C9-C10 terpenoids is required, and/or when concentrations of anthropogenic VOC are significant). These analysis times potentially allow for a twofold to fivefold increase in measurement frequency compared to conventional GC methods. Here we outline the technical details and analytical capability of this chromatographic approach, and present the first in-situ Fast-GC observations of 6 monoterpenes and the oxygenated BVOC (OBVOC) linalool in ambient air. During this field deployment within a suburban forest ~30 km west of central Tokyo, Japan, the Fast-GC limit of detection with respect to monoterpenes was 4–5 ppt, and the agreement between Fast-GC and PTR-MS derived total monoterpene mixing ratios was consistent with previous GC/PTR-MS comparisons. The measurement uncertainties associated with the Fast-GC quantification of monoterpenes are ≤ 12%, while larger uncertainties (up to ~25%) are associated with the OBVOC and sesquiterpene measurements.

We present a detailed analysis of OH observations from the BEACHON (Bio-hydro-atmosphere interactions of Energy, Aerosols, Carbon, H2O, Organics and Nitrogen)-ROCS (Rocky Mountain Organic Carbon Study) 2010 field campaign at the Manitou Forest Observatory (MFO), which is a 2-methyl-3-butene-2-ol (MBO) and monoterpene (MT) dominated forest environment. A comprehensive suite of measurements was used to constrain primary production of OH via ozone photolysis, OH recycling from HO2, and OH chemical loss rates, in order to estimate the steady-state concentration of OH. In addition, the University of Washington Chemical Model (UWCM) was used to evaluate the performance of a near-explicit chemical mechanism. The diurnal cycle in OH from the steady-state calculations is in good agreement with measurement. A comparison between the photolytic production rates and the recycling rates from the HO2 + NO reaction shows that recycling rates are ~20 times faster than the photolytic OH production rates from ozone. Thus, we find that direct measurement of the recycling rates and the OH loss rates can provide accurate predictions of OH concentrations. More importantly, we also conclude that a conventional OH recycling pathway (HO2 + NO) can explain the observed OH levels in this non-isoprene environment. This is in contrast to observations in isoprene-dominated regions, where investigators have observed significant underestimation of OH and have speculated that unknown sources of OH are responsible. The highly-constrained UWCM calculation under-predicts observed HO2 by as much as a factor of 8. As HO2 maintains oxidation capacity by recycling to OH, UWCM underestimates observed OH by as much as a factor of 4. When the UWCM calculation is constrained by measured HO2, model calculated OH is in better agreement with the observed OH levels. Conversely, constraining the model to observed OH only slightly reduces the model-measurement HO2 discrepancy, implying unknown HO2 sources. These findings demonstrate the importance of constraining the inputs to, and recycling within, the ROx radical pool (OH + HO2 + RO2).

N2O5 detection in the atmosphere has been accomplished using techniques which have been developed during the last decade. Most techniques use a heated inlet to thermally decompose N2O5 to NO3, which can be detected by either cavity based absorption at 662 nm or by laser-induced fluorescence. In summer 2007, a large set of instruments, which were capable of measuring NO3 mixing ratios, were simultaneously deployed in the atmosphere simulation chamber SAPHIR in Jülich, Germany. Some of these instruments measured N2O5 mixing ratios either simultaneously or alternatively. Experiments focused on the investigation of potential interferences from, e.g., water vapour or aerosol and on the investigation of the oxidation of biogenic volatile organic compounds by NO3. The comparison of N2O5 mixing ratios shows an excellent agreement between measurements of instruments applying different techniques (3 cavity ring-down (CRDS) instruments, 2 laser-induced fluorescence (LIF) instruments). Datasets are highly correlated as indicated by the square of the linear correlation coefficients, R2, which values were larger than 0.96 for the entire datasets. N2O5 mixing ratios well agree within the combined accuracy of measurements. Slopes of the linear regression range between 0.87 and 1.26 and intercepts are negligible. The most critical aspect of N2O5 measurements by cavity ring-down instruments is the determination of the inlet and filter transmission efficiency. Measurements here show that the N2O5 inlet transmission efficiency can decrease in the presence of high aerosol loads, and that frequent filter/inlet changing is necessary to quantitatively sample N2O5 in some environments. The analysis of data also demonstrates that a general correction for degrading filter transmission is not applicable for all conditions encountered during this campaign. Besides the effect of a gradual degradation of the inlet transmission efficiency aerosol exposure, no other interference for N2O5 measurements is found.

We report the first observations of formaldehyde (HCHO) flux measured via eddy covariance, as well as HCHO concentrations and gradients, as observed by the Madison Fiber Laser-Induced Fluorescence Instrument during the BEACHON-ROCS 2010 campaign in a rural, Ponderosa Pine forest northwest of Colorado Springs, CO. A median noon upward flux of ~80 μg m−2 h−1 (~24 pptv m s−1) was observed with a noon range of 37 to 131 μg m−2 h−1. Enclosure experiments were performed to determine the HCHO branch (3.5 μg m-2 h−1) and soil (7.3 μg m−2 h−1) direct emission rates in the canopy. A zero-dimensional canopy box model, used to determine the apportionment of HCHO source and sink contributions to the flux, underpredicted the observed HCHO flux by a factor of 6. Simulated increases in concentrations of species similar to monoterpenes resulted in poor agreement with measurements, while simulated increases in direct HCHO emissions and/or concentrations of species similar to 2-methyl-3-buten-2-ol best improved model/measurement agreement. Given the typical diurnal variability of these BVOC emissions and direct HCHO emissions, this suggests that the source of the missing flux is a process with both a strong temperature and radiation dependence.

OH reactivity is one of key indicators which reflect impacts of photochemical reactions in the atmosphere. An observation campaign has been conducted in the summer of 2007 at the heart of Tokyo metropolitan area to measure OH reactivity. The total OH reactivity measured directly by the laser-induced pump and probe technique was higher than the sum of the OH reactivity calculated from concentrations and reaction rate coefficients of individual species measured in this campaign. And then, three-dimensional air quality simulation has been conducted to evaluate the simulation performance on the total OH reactivity including "missing sinks", which correspond to the difference between the measured and calculated total OH reactivity. The simulated OH reactivity is significantly underestimated because the OH reactivity of volatile organic compounds (VOCs) and missing sinks are underestimated. When scaling factors are applied to input emissions and boundary concentrations, a good agreement is observed between the simulated and measured concentrations of VOCs. However, the simulated OH reactivity of missing sinks is still underestimated. Therefore, impacts of unidentified missing sinks are investigated through sensitivity analyses. In the cases that unknown secondary products are assumed to account for unidentified missing sinks, they tend to suppress formation of secondary aerosol components and enhance formation of ozone. In the cases that unidentified primary emitted species are assumed to account for unidentified missing sinks, a variety of impacts may be observed, which could serve as precursors of secondary organic aerosols (SOA) and significantly increase SOA formation. Missing sinks are considered to play an important role in the atmosphere over Tokyo metropolitan area.