12 research outputs found
The equation of state of solid nickel aluminide
The pressure-volume-temperature equation of state of the intermetallic
compound NiAl was calculated theoretically, and compared with experimental
measurements. Electron ground states were calculated for NiAl in the CsCl
structure, using density functional theory, and were used to predict the cold
compression curve and the density of phonon states. The Rose form of
compression curve was found to reproduce the ab initio calculations well in
compression but exhibited significant deviations in expansion. A
thermodynamically-complete equation of state was constructed for NiAl. Shock
waves were induced in crystals of NiAl by the impact of laser-launched Cu
flyers and by launching NiAl flyers into transparent windows of known
properties. The TRIDENT laser was used to accelerate the flyers to speeds
between 100 and 600m/s. Point and line-imaging laser Doppler velocimetry was
used to measure the acceleration of the flyer and the surface velocity history
of the target. The velocity histories were used to deduce the stress state, and
hence states on the principal Hugoniot and the flow stress. Flyers and targets
were recovered from most experiments. The effect of elasticity and plastic flow
in the sample and window was assessed. The ambient isotherm reproduced static
compression data very well, and the predicted Hugoniot was consistent with
shock compression data
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Properties of Ni-Al under shock loading
New models for the dynamic response of materials will be based increasingly on better understanding and representation of processes occurring at the microstructural level. These developments require advances in diagnostics and models which can be applied explicitly to microstructural response. Various phenomena occur at the microstructural level which are generally ignored or averaged out in continuum-level models. One example of such 'irregular hydrodynamics' is the roughness imparted to a shock wave as it propagates through a polycrystalline material. We have developed imaging techniques to study spatial variations in shock propagation through polycrystalline materials. In order to interpret spatially-resolved data from polycrystal samples, we need to compare with simulations which represent the microstructure. Here we describe work undertaken to develop a model of the dynamic response of individual grains. The material chosen was Ni-Al alloy, because it exhibits a relatively large degree of elastic anisotropy, and it is relatively easy to manufacture
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
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
Photographic Studies of Laser-Induced Bubble Formation in Absorbing Liquids and on Submerged Targets: Implications for Drug Delivery with Microsecond Laser Pulses
Pulsed laser ablation of blood clots in a fluid-filled blood vessel is accompanied by an explosive evaporation process. The resulting vapor bubble rapidly expands and collapses to disrupt the thrombus (blood clot). The hydrodynamic pressures following the bubble expansion and collapse can also be used as a driving force to deliver clot-dissolving agents into thrombus for enhancement of laser thrombolysis. Thus, the laser-induced bubble formation plays an important role in the thrombus removal process. We investigate the effects of boundary configurations and materials on bubble formation with time-resolved flash photography and high-speed photography. Potential applications in drug delivery using microsecond laser pulses are also discussed
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Multiscale modeling of beryllium: quantum mechanics and laser-driven shock experiments using novel diagnostics.
Ab initio quantum mechanics was used to construct a thermodynamically complete and rigorous equation of state for beryllium in the hexagonal and body-centred cubic structures, and to predict elastic constants as a function of compression. The equation of state agreed well with Hugoniot data and previously-published equations of state, but the temperatures were significantly different. The hexagonal/bcc phase boundary agreed reasonably well with published data, suggesting that the temperatures in our new equation of state were accurate. Shock waves were induced in single crystals and polycrystalline foils of beryllium, by direct illumination using the TRIDENT laser at Los Alamos. The velocity history at the surface of the sample was measured using a line-imaging VISAR, and transient X-ray diffraction (TXD) records were obtained with a plasma backlighter and X-ray streak cameras. The VISAR records exhibited elastic precursors, plastic waves, phase changes and spall. Dual TXD records were taken, in Bragg and Laue orientations. The Bragg lines moved in response to compression in the uniaxial direction. Because direct laser drive was used, the results had to be interpreted with the aid of radiation hydrodynamics simulations to predict the loading history for each laser pulse. In the experiments where there was evidence of polymorphism in the VISAR record, additional lines appeared in the Bragg and Laue records. The corresponding pressures were consistent with the phase boundary predicted by the quantum mechanical equation of state for beryllium. A model of the response of a single crystal of beryllium to shock loading is being developed using these new theoretical and experimental results. This model will be used in meso-scale studies of the response of the microstructure, allowing us to develop a more accurate representation of the behaviour of polycrystalline beryllium
Sapphire (0001) surface modifications induced by long-pulse 1054 nm laser irradiation
We have investigated modifications of sapphire (0 0 0 1) surface with and without coating, induced by a single laser pulse with a 1054 nm wavelength, 2.2 µs sources duration, 7.75 mm spot and energy of 20–110 J. A holographic optical element was used for smoothing the drive beam spatially, but it induced small hotspots which initiated damage on the uncoated and coated surfaces. The individual damage effects of hotspots became less pronounced at high fluences. Due to high temperature and elevated non-hydrostatic stresses upon laser irradiation, damage occurred as fracture, spallation, basal and rhombohedral twinning, melting, vitrification, the formation of nanocrystalline phases, and solid–solid phase transition. The extent of damage increased with laser fluences. The formation of regular linear patterns with three-fold symmetry (1 1 2^[bar] 0) upon fracture was due to rhombohedral twinning. Nanocrystalline α-Al_2O_3 formed possibly from vapor deposition on the coated surface and manifested linear, triangular and spiral growth patterns. Glass and minor amounts of γ-Al_2O_3 also formed from rapid quenching of the melt on this side. The α- to γ-Al_2O_3 transition was observed on the uncoated surface in some partially spalled alumina, presumably caused by shearing. The nominal threshold for laser-induced damage is about 47 J cm^(−2) for these laser pulses, and it is about 94 J cm^(−2) at the hotspots
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High-speed optical diagnostics for material studies and laser/matter interactions
No abstract prepared
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Laser/matter interactions by laser-launched plates and direct laser shocks
Explosives, gas guns, laser-launched flyer plates, and direct laser-irradiation can be used to generate shocks and high-stress in materials. Each method has a unique diameter and thickness of shock that can be generated. In past years, small laboratory lasers have been used to launch flyer plates 2 - 200-pm thick to terminal velocities 0.1 to 5 k d s . Over the past few years we have been using our TRIDENT laser facility (1kJ in 0.2 to 2ps) to accelerate larger diameter (8 mm) and thicker (0.1 - 1.5 mm) flyer plates. These larger diameters and thicker one-dimensional plates more closely compliment traditional experimental methods such as gas guns. The 8-mm diameter and 1-mm thick flyer plates can impart shocks in metals for constitutive dynamic property measurements. The versatility of laser-driven plates permits spatial and temporal profiles of the flyer plate impact on sample targets. LASNEX models and parameters of the laser drive can be used to optimize optical coupling efficiency. The flyer plate launch, acceleration, terminal velocity, and, depending on the experiment, flyer plate impact on to target materials are recorded using point-interferometry (VISAR), and line-imaging interferometry. These high speed optical and laser experimental methods will be described along with ancillary methods, and material data. Constitutive properties of bulk materials, rate effects, and grain size and/or orientation have been studied for several metals including copper, beryllium, gold, and some alloys