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At least 235 records · Page 13

Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer

Purpose: Radiation therapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumor control in esophageal cancer; however, any increase in acute hematologic toxicity (HT) could limit the predicted improvement in patient outcomes. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy. Therefore, we investigated the potential of bone marrow sparing with protons for esophageal tumors. Methods and Materials: Twenty-one patients with mid-esophageal cancer who had undergone conformal radiation therapy (3D50) were selected. Two surrogates for bone marrow were created by outlining the thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse. The percentage of overlap of the TV with the planning treatment volume was recorded for each patient. Additional plans were created retrospectively, including a volumetric modulated arc therapy (VMAT) plan with the same dose as for 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high-risk subregion within the planning treatment volume; a reoptimized TV-sparing VMAT plan; and a proton therapy plan with the same SIB dose prescription. The bone and TV dose metrics were recorded and compared across all plans and variations with respect to PTV and percentage of overlap for each patient. Results: The 3D50 plans showed the highest bone mean dose and TV percentage of volume receiving ≥30 Gy (V{sub 30Gy}) for each patient. The VMAT plans irradiated a larger bone V{sub 10Gy} than did the 3D50 plans. The reoptimized VMAT62.5 VT plans showed improved sparing of the TV volume, but only the proton plans showed significant sparing for bone V{sub 10Gy} and bone mean dose, especially for patients with a larger PTV. Conclusions: The results of the present study have shown that proton therapy can reduced bone marrow toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Phase 1 Dose Escalation Study of Neoadjuvant SBRT Plus Elective Nodal Radiation with Concurrent Capecitabine for Resectable Pancreatic Cancer

The role of neoadjuvant radiation for resectable pancreatic adenocarcinoma is controversial. We performed a prospective dose-escalation study of neoadjuvant stereotactic body radiation therapy (SBRT) with concurrent capecitabine and elective nodal irradiation (ENI) followed by surgical resection to explore the toxicity and feasibility of this approach.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Moderately Hypofractionated Once-Daily Compared With Twice-Daily Thoracic Radiation Therapy Concurrently With Etoposide and Cisplatin in Limited-Stage Small Cell Lung Cancer: A Multicenter, Phase II, Randomized Trial

Chemotherapy and concurrent thoracic radiation therapy (CCTRT) followed by prophylactic cranial irradiation (PCI) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). We aimed to compare the efficacy and toxicity of moderately hypofractionated once-daily CCTRT with that of a standard twice-daily regimen.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Concurrent characterization of GaN MOSHEMT gate leakage via electrical and thermoreflectance measurements

In this work, we report the first concurrent use of electrical and thermal characterization, via thermoreflectance, to analyze Time Dependent Dielectric Breakdown in GaN MOSHEMTs. Electrically stressing the devices until a failure occurs, then evaluating them via thermoreflectance, revealed a geometric dependence of the failure mode. Further, all soft breakdowns occurred at the mesa edge where the electric field strength was at its strongest, and tunneling current density was at its highest. This breakdown phenomenon at the mesa edge has been seen previously in GaN HEMTs employing a mesa architecture. Possible approaches to mitigate these failures in MOSHEMTs are proposed.

42 ENGINEERING↗

Atomic insight into concurrent He, D, and T sputtering and near-surface implantation of 3C-SiC crystallographic surfaces

We present results from atomistic simulations of sputtering and near-surface implantation of concurrent He, D, and T bombardment of cubic silicon carbide (3C-SiC). This is achieved by first establishing a many-body interatomic potential parameter set to treat interactions of He and hydrogenic species in 3C-SiC informed by ab-initio calculations. To obtain sputtering yields we perform both classical molecular dynamics and binary collision approximation simulations for normal incident particles having energies ranging from 25 to 800 eV. We find that due to differences in species surface binding energy of various crystallographic surfaces in 3C-SiC, the sputtering yield of Si is significantly less than that of C, but sputtering yields show limited sensitivity to crystallographic surface orientation. An exception to this occurs when the terminating crystallographic surface plane is more rich in Si rather than C, resulting in comparable sputtering yields of Si and C. The influence of temperature on sputtering is explored and shows limited effect. Finally, the nature of implanted He, D, and T within 3C-SiC surfaces is investigated to understand implantation profiles and stability of defects.

36 MATERIALS SCIENCE↗

Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 μg/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 μg/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ► Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ► Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ► BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ► BPA levels in monkey placenta are similar to other metabolically active tissues. ► Some published human cord blood data for BPA are inconsistent with these measurements.

60 APPLIED LIFE SCIENCES↗

The functional potency of natural killer cells in response to IL-2/IL-15/IL-21 stimulation is limited by a concurrent upregulation of Tim-3 in bladder cancer

Highlights: • NK cells from bladder cancer patients presented significant Tim-3 upregulation. • NK cells from bladder cancer patients presented significantly reduced cytotoxicity. • Cytokine-mediated stimulatory effects were less potent in bladder cancer patients. • Treatment with cytokines increased the expression of Tim-3 by NK cells. • Tim-3 blockade allowed the NK cells to present higher cytotoxicity in patients. For reasons not completely clear, natural killer (NK) cells from tumor patients displayed multiple exhaustion features and could not be completely restored even when the inhibitory signals from the intratumoral environment had ceased to exist. Here, we found that the circulating NK cells from bladder cancer patients presented significantly reduced cytotoxicity than the circulating NK cells from healthy volunteers. This impairment in cytotoxicity resulted in part from an overrepresentation of Tim-3{sup +} NK cells in bladder cancer patients. Interestingly, patients with higher frequency of Tim-3{sup +} NK cells tended to present higher frequency of Gal-9{sup +} cells in tumor. Exogenous Gal-9 significantly reduced the cytotoxicity of Tim-3{sup +}, but not Tim-3{sup -}, NK cells. Patients with better prognosis presented lower levels of Tim-3{sup +} NK cells and Gal-9{sup +} tumor cells. We then attempted to improve the cytotoxicity of NK cells using a combination of exogenous cytokines. IL-2 + IL-15 and IL-2 + IL-21 significantly enhanced, but could not completely restore, the cytotoxicity of NK cells in bladder cancer patients. Notably, when the cytokine concentration increased from intermediate levels to high levels, the cytotoxicity of NK cells from healthy volunteers significantly increased with a strong upward trend, whereas the cytotoxicity of NK cells from bladder cancer patients plateaued at intermediate levels. Further examination revealed that high cytokine concentration significantly increased the Tim-3 expression in NK cells from bladder cancer patients. Blocking Tim-3 not only improved the cytotoxicity of NK cells from bladder cancer patients, but also eliminated the plateauing effect when the NK cells were stimulated with high concentrations of cytokines. Together, these data suggested that proinflammatory cytokines could moderately improve NK cell cytotoxicity in bladder cancer patients. However, the effect was limited due to a concurrent upregulation of Tim-3.

60 APPLIED LIFE SCIENCES↗

Sequential slip transfer of mixed-character dislocations across Σ3 coherent twin boundary in FCC metals: a concurrent atomistic-continuum study

Sequential slip transfer across grain boundaries (GB) has an important role in size-dependent propagation of plastic deformation in polycrystalline metals. For example, the Hall–Petch effect, which states that a smaller average grain size results in a higher yield stress, can be rationalised in terms of dislocation pile-ups against GBs. In spite of extensive studies in modelling individual phases and grains using atomistic simulations, well-accepted criteria of slip transfer across GBs are still lacking, as well as models of predicting irreversible GB structure evolution. Slip transfer is inherently multiscale since both the atomic structure of the boundary and the long-range fields of the dislocation pile-up come into play. In this work, concurrent atomistic-continuum simulations are performed to study sequential slip transfer of a series of curved dislocations from a given pile-up on Σ3 coherent twin boundary (CTB) in Cu and Al, with dominant leading screw character at the site of interaction. A Frank-Read source is employed to nucleate dislocations continuously. It is found that subject to a shear stress of 1.2 GPa, screw dislocations transfer into the twinned grain in Cu, but glide on the twin boundary plane in Al. Moreover, four dislocation/CTB interaction modes are identified in Al, which are affected by (1) applied shear stress, (2) dislocation line length, and (3) dislocation line curvature. Our results elucidate the discrepancies between atomistic simulations and experimental observations of dislocation-GB reactions and highlight the importance of directly modeling sequential dislocation slip transfer reactions using fully 3D models.

36 MATERIALS SCIENCE↗

Concurrence of superconductivity and structure transition in Weyl semimetal TaP under pressure

Weyl semimetal defines a material with three-dimensional Dirac cones, which appear in pair due to the breaking of spatial inversion or time reversal symmetry. Superconductivity is the state of quantum condensation of paired electrons. Turning a Weyl semimetal into superconducting state is very important in having some unprecedented discoveries. In this work, by doing resistive measurements on a recently recognized Weyl semimetal TaP under pressures up to about 100 GPa, we show the concurrence of superconductivity and a structure transition at about 70 GPa. It is found that the superconductivity becomes more pronounced when decreasing pressure and retains when the pressure is completely released. High-pressure x-ray diffraction measurements also confirm the structure phase transition from I41md to P-6m2 at about 70 GPa. More importantly, ab-initial calculations reveal that the P-6m2 phase is a new Weyl semimetal phase and has only one set of Weyl points at the same energy level. Our discovery of superconductivity in TaP by high pressure will stimulate investigations on superconductivity and Majorana fermions in Weyl semimetals.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Concurrence of quantum anomalous Hall and topological Hall effects in magnetic topological insulator sandwich heterostructures

The quantum anomalous Hall (QAH) effect is a consequence of non-zero Berry curvature in momentum space. The QAH insulator harbours dissipation-free chiral edge states in the absence of an external magnetic field. Yet, the topological Hall (TH) effect, a hallmark of chiral spin textures, is a consequence of real-space Berry curvature. Herein, by inserting a topological insulator (TI) layer between two magnetic TI layers, we realized the concurrence of the TH effect and the QAH effect through electric-field gating. The TH effect is probed by bulk carriers, whereas the QAH effect is characterized by chiral edge states. The appearance of the TH effect in the QAH insulating regime is a consequence of chiral magnetic domain walls that result from the gate-induced Dzyaloshinskii–Moriya interaction and occurs during the magnetization reversal process in the magnetic TI sandwich samples. The coexistence of chiral edge states and chiral spin textures provides a platform for proof-of-concept dis- sipationless spin-textured spintronic applications.

36 MATERIALS SCIENCE↗