Transgranular Cracking in a Liquid Zn Embrittled High Strength Steel.

Intergranular Zn-assisted liquid metal embrittlement (LME) cracks have been frequently reported in steels, involving austenite grain boundary penetration of liquid Zn at high temperature. In the present study, a Zn-coated high strength steel was deformed at an intercritical temperature, and the characteristics of LME cracking were studied in a mixed microstructure composed of ferrite and austenite. Crack propagation was intergranular in austenite; in contrast, the ferrite exhibited both intergranular LME and transgranular LME. Trace analysis of the crack plane orientation was consistent with cracking along {100} cleavage planes in ferrite.

Focused Ion Beam-Induced Displacive Phase Transformation From Austenite to Martensite during Fabrication of Quenched and Partitioned Steel Micro-Pillar.

We report evidence of a displacive phase transformation from retained austenite to martensite during preparation of quenched and partitioned steel micro-pillars by using a focused ion beam (FIB) technique. The BCC phase produced by the FIB damage was identified as martensite. The invariant-plane strain surface relief associated with the martensitic transformation was observed in the retained austenite phase immediately after a FIB scan of the surface with the Ga+ ion beam. Use of a low acceleration voltage appears to lower the probability of the phase transformation, while a decrease of the acceleration voltage will result in an increase of the total milling time required to prepare a micro-pillar. This report addresses challenges related to the preparation of austenite micro-pillars by a conventional FIB technique.

Effects of Al-Si Coating and Zn Coating on the Hydrogen Uptake and Embrittlement of Ultra-High Strength Press-Hardened Steel.

Press-hardened steel (PHS), used for automotive safety-related structure parts, is sensitive to hydrogen embrittlement due to its martensitic microstructure. Hydrogen is introduced in PHS during the hot press forming (HPF) process, by an atmospheric corrosion process. In this study, the hydrogen embrittlement behavior of uncoated, aluminized, and galvanized PHSs was investigated. The Al-10%Si coating promoted the absorption of diffusible hydrogen at elevated temperature during the HPF while the reacted coating layer prevented the absorbed hydrogen from out-diffusing through the reacted coating surface layer at room temperature. Therefore, the aluminized PHS showed a greater sensitivity to both the hydrogen uptake and the resultant embrittlement, as compared to the uncoated and galvanized PHSs. Use of galvanized PHS for HPF application reduces the risk of hydrogen embrittlement, since the Zn coating effectively prevents the hydrogen uptake. The greater embrittlement resistance of the galvanized PHS is possibly due to the inhibition of the hydrogen generation reaction by the surface ZnO oxide layer and the low rate of hydrogen transport through the liquid Zn phase.

Trends in the use of pre-operative radiation for adenocarcinoma of the pancreas in the United States.

BACKGROUND: The benefit and timing of radiation therapy (RT) for patients undergoing a resection for pancreatic adenocarcinoma remains unclear. This study identifies trends in the use of radiation over a 10-year period and factors associated with the use of pre-operative radiation, in particular. METHODS: The Surveillance, Epidemiology and End Results registry was used to identify patients aged ≥18 years with pancreatic adenocarcinoma who underwent a surgical resection between 2000 and 2010. Logistic regression was used to identify time trends and factors associated with the use of pre-operative radiation. RESULTS: The overall use of radiation decreased with time among the 8474 patients who met the inclusion criteria. However, the use of pre-operative radiation increased from 1.8% to 3.9% (P ≤ 0.05). Factors significantly associated with receipt of pre-operative radiation were younger age, treatment in more recent years and having an advanced T-stage tumour. The 5-year hazard of death was significantly less for those who received pre-operative radiation versus surgery alone [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55-0.74] and for those who received post-operative radiation versus surgery alone (HR 0.69, 95% CI 0.65-0.73). DISCUSSION: The use of pre-operative radiation significantly increased during the study period. However, the overall use of pre-operative radiation therapy remains low in spite of the potential benefits.

HIF-1α Inhibition Improves Anti-Tumor Immunity and Promotes the Efficacy of Stereotactic Ablative Radiotherapy (SABR).

High-dose hypofractionated radiation such as SABR (stereotactic ablative radiotherapy) evokes an anti-tumor immune response by promoting a series of immune-stimulating processes, including the release of tumor-specific antigens from damaged tumor cells and the final effector phase of immune-mediated lysis of target tumor cells. High-dose hypofractionated radiation also causes vascular damage in tumors, thereby increasing tumor hypoxia and upregulation of hypoxia-inducible factors HIF-1α and HIF-2α, the master transcription factors for the cellular response to hypoxia. HIF-1α and HIF-2α are critical factors in the upregulation of immune suppression and are the master regulators of immune evasion of tumors. Consequently, SABR-induced increase in anti-tumor immunity is counterbalanced by the increase in immune suppression mediated by HIFα. Inhibition of HIF-1α with small molecules such as metformin downregulates immunosuppressive pathways, including the expression of immune checkpoints, and it improves or restores the anti-tumor immunity stimulated by irradiation. Combinations of HIFα inhibitors, particularly HIF-1α inhibitors, with immune checkpoint blocking antibodies may represent a novel approach to boost the overall anti-tumor immune profile in patients and thus enhance outcomes after SABR.

Effect of lung and target density on small-field dose coverage and PTV definition.

We have studied the effect of target and lung density on block margin for small stereotactic body radiotherapy (SBRT) targets. A phantom (50 × 50 × 50cm(3)) was created in the Pinnacle (V9.2) planning system with a 23-cm diameter lung region of interest insert. Diameter targets of 1.6, 2.0, 3.0, and 4.0cm were placed in the lung region of interest and centered at a physical depth of 15cm. Target densities evaluated were 0.1 to 1.0g/cm(3), whereas the surrounding lung density was varied between 0.05 and 0.6g/cm(3). A dose of 100cGy was delivered to the isocenter via a single 6-MV field, and the ratio of the average dose to points defining the lateral edges of the target to the isocenter dose was recorded for each combination. Field margins were varied from none to 1.5cm in 0.25-cm steps. Data obtained in the phantom study were used to predict planning treatment volume (PTV) margins that would match the clinical PTV and isodose prescription for a clinical set of 39 SBRT cases. The average internal target volume (ITV) density was 0.73 ± 0.17, average local lung density was 0.33 ± 0.16, and average ITV diameter was 2.16 ± 0.8cm. The phantom results initially underpredicted PTV margins by 0.35cm. With this offset included in the model, the ratio of predicted-to-clinical PTVs was 1.05 ± 0.32. For a given target and lung density, it was found that treatment margin was insensitive to target diameter, except for the smallest (1.6-cm diameter) target, for which the treatment margin was more sensitive to density changes than the larger targets. We have developed a graphical relationship for block margin as a function of target and lung density, which should save time in the planning phase by shortening the design of PTV margins that can satisfy Radiation Therapy Oncology Group mandated treatment volume ratios.

Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery.

Despite the increasing use of stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS) in recent years, the biological base of these high-dose hypo-fractionated radiotherapy modalities has been elusive. Given that most human tumors contain radioresistant hypoxic tumor cells, the radiobiological principles for the conventional multiple-fractionated radiotherapy cannot account for the high efficacy of SBRT and SRS. Recent emerging evidence strongly indicates that SBRT and SRS not only directly kill tumor cells, but also destroy the tumor vascular beds, thereby deteriorating intratumor microenvironment leading to indirect tumor cell death. Furthermore, indications are that the massive release of tumor antigens from the tumor cells directly and indirectly killed by SBRT and SRS stimulate anti-tumor immunity, thereby suppressing recurrence and metastatic tumor growth. The reoxygenation, repair, repopulation, and redistribution, which are important components in the response of tumors to conventional fractionated radiotherapy, play relatively little role in SBRT and SRS. The linear-quadratic model, which accounts for only direct cell death has been suggested to overestimate the cell death by high dose per fraction irradiation. However, the model may in some clinical cases incidentally do not overestimate total cell death because high-dose irradiation causes additional cell death through indirect mechanisms. For the improvement of the efficacy of SBRT and SRS, further investigation is warranted to gain detailed insights into the mechanisms underlying the SBRT and SRS.