Surface Roughness of Electron Beam Melting TI-6AL-4V Effect on Ultrasonic Testing

Experimental research was conducted on the effects of surface roughness on ultrasonic non-destructive testing of Electron Beam Melted (EBM) additively manufactured Ti-6Al-4V. Additive Manufacturing (AM) is a developing technology with many potential benefits, but certain challenges posed by its use require further research before AM parts are viable for widespread use in the aviation industry. Possible applications of this new technology include, Aircraft Battle Damage Repair (ABDR), small batch manufacturing to fill supply gaps, and replacement for obsolete parts. The research presented here assesses the effectiveness of ultrasonic inspection in detecting manufactured flaws in EBM manufactured Ti-6Al-4V. EBM products are known to have high surface roughness in as-manufactured condition, and surface roughness is known to affect the results of ultrasonic inspections. The experimental data from this research demonstrates the ability of ultrasonic inspections to identify flaws as small as 0.51 mm at 2.25 MHz, 5 MHz and 10 MHz through a machined surface. A frequency of 10 MHz provides better results than 2.25 MHz and 5 MHz through an as manufactured surface, where the highest natural surface roughness is present

Effect of Surface Roughness on Ultrasonic Inspection of Electron Beam Melting Ti‐6AL‐4V

Experimental research was conducted on the effects of surface roughness on ultrasonic non-destructive testing of electron beam melted (EBM) additively manufactured Ti-6Al-4V. Additive manufacturing (AM) is a developing technology with many potential benefits, but certain challenges posed by its use require further research before AM parts are viable for widespread use in the aviation industry. Possible applications of this new technology include aircraft battle damage repair (ABDR), small batch manufacturing to fill supply gaps and replacement for obsolete parts. This paper aims to assess the effectiveness of ultrasonic inspection in detecting manufactured flaws in EBM-manufactured Ti-6Al-4V. Additively manufactured EBM products have a high surface roughness in “as-manufactured” condition which is an artifact of the manufacturing process. The surface roughness is known to affect the results of ultrasonic inspections. Experimental data from this research demonstrate the ability of ultrasonic inspections to identify imbedded flaws as small as 0.51 mm at frequencies of 2.25, 5 and 10 MHz through a machined surface. Detection of flaws in higher surface roughness samples was increased at a frequency of 10 MHz opposed to both lower frequencies tested

Approaching the motional ground state of a 10 kg object

The motion of a mechanical object -- even a human-sized object -- should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult: the thermal environment masks any quantum signature of the object's motion. Indeed, the thermal environment also masks effects of proposed modifications of quantum mechanics at large mass scales. We prepare the center-of-mass motion of a 10 kg mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in temperature, from room temperature to 77 nK, is commensurate with an 11 orders-of-magnitude suppression of quantum back-action by feedback -- and a 13 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state. This begets the possibility of probing gravity on massive quantum systems.Comment: published version containing minor change

Identification and mitigation of narrow spectral artifacts that degrade searches for persistent gravitational waves in the first two observing runs of Advanced LIGO

Searches are under way in Advanced LIGO and Virgo data for persistent gravitational waves from continuous sources, e.g. rapidly rotating galactic neutron stars, and stochastic sources, e.g. relic gravitational waves from the Big Bang or superposition of distant astrophysical events such as mergers of black holes or neutron stars. These searches can be degraded by the presence of narrow spectral artifacts (lines) due to instrumental or environmental disturbances. We describe a variety of methods used for finding, identifying and mitigating these artifacts, illustrated with particular examples. Results are provided in the form of lists of line artifacts that can safely be treated as non-astrophysical. Such lists are used to improve the efficiencies and sensitivities of continuous and stochastic gravitational wave searches by allowing vetoes of false outliers and permitting data cleaning

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

TIP30 has an intrinsic kinase activity required for up-regulation of a subset of apoptotic genes

CC3 is a metastasis suppressor that inhibits metastasis of the variant small cell lung carcinoma (v-SCLC) by predisposing cells to apoptosis. The same protein was also reported as a cellular cofactor, TIP30, which stimulates HIV-1 Tat-activated transcription by interacting with both Tat and RNA polymerase II. We report here that TIP30/CC3 is a novel serine/threonine kinase. It phosphorylates the heptapeptide repeats of the C-terminal domain (CTD) of the largest RNA polymerase II subunit in a Tat-dependent manner. Amino acid substitutions in the putative ATP binding motif that abolish the TIP30 kinase activity also inhibit the ability of TIP30 to enhance Tat-activated transcription or to sensitize NIH 3T3 and v-SCLC cells to apoptosis. Furthermore, ectopic expression of TIP30/CC3 in v–SCLC cells induces expression of a number of genes that include the apoptosis-related genes Bad and Siva, as well as metastasis suppressor NM23-H2. These data demonstrate a molecular mechanism for TIP30/CC3 function and suggest a novel pathway for regulating apoptosis