Characterization of Laser-Generated Aluminum Plasma Using Ion Time-of-Flight and Optical Emission Spectroscopy

Laser plasma generated by ablation of an Al target in vacuum is characterized by ion time-of-flight combined with optical emission spectroscopy. A Q-switched Nd:YAG laser (wavelength λ = 1064 nm, pulse width τ ∼ 7 ns, and fluence F ≤ 38 J/cm2) is used to ablate the Al target. Ion yield and energy distribution of each charge state are measured. Ions are accelerated according to their charge state by the double-layer potential developed at the plasma-vacuum interface. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. Optical emission spectroscopy of the Al plasma gives significantly lower plasma temperature than the ion temperature obtained from the ion time-of-flight, due to the difference in the temporal and spatial regions of the plasma plume probed by the two methods. Applying an external electric field in the plasma expansion region in a direction parallel to the plume expansion increases the line emission intensity. However, the plasma temperature and density, as measured by optical emission spectroscopy, remain unchanged

Spark Discharge Coupled Laser Multicharged Ion Source

A spark discharge is coupled to a laser multicharged ion source to enhance ion generation. The laser plasma triggers a spark discharge with electrodes located in front of the ablated target. For an aluminum target, the spark discharge results in significant enhancement in the generation of multicharged ions along with higher charge states than observed with the laser source alone. When a Nd:YAG laser pulse (wavelength 1064 nm, pulse width 7.4 ns, pulse energy 72 mJ, laser spot area on target 0.0024 cm2) is used, the total multicharged ions detected by a Faraday cup is 1.0 nC with charge state up to Al3+. When the spark amplification stage is used (0.1 μF capacitor charged to 5.0 kV), the total charge measured increases by a factor of ∼9 with up to Al6+ charge observed. Using laser pulse energy of 45 mJ, charge amplification by a factor of ∼13 was observed for a capacitor voltage of 4.5 kV. The spark discharge increases the multicharged ion generation without increasing target ablation, which solely results from the laser pulse. This allows for increased multicharged ion generation with relatively low laser energy pulses and less damage to the surface of the target. © 2015 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4923457

Aluminum Multicharged Ion Generation from Femtosecond Laser Plasma

Aluminum multicharged ion generation from femtosecond laser ablation is studied. A Ti:sapphire laser (wavelength 800 nm, pulse width ∼100 fs, and maximum laser fluence of 7.6 J/cm2) is used. Ion yield and energy distribution of each charge state are measured. A linear relationship between the ion charge state and the equivalent acceleration energy of the individual ion species is observed and is attributed to the presence of an electric field within the plasma-vacuum boundary that accelerates the ions. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. For Al1+ and Al2+, the ion energy distributions have two components; the faster one can be attributed to multiphoton laser ionization, while the slower one is possibly due to collisional processes. Ion extraction from the plasma is increased with an applied external electric field, which is interpreted to be due to the retrograde motion of the plasma edge as a result of the external electric field. Multicharged ion generation by femtosecond laser ablation is compared to previously reported ion generation with nanosecond laser ablation and is shown to require significantly lower laser fluence and generates higher charge states and more energetic ions. © 2017 Author(s)

Evidence for B cell exhaustion in chronic graft-versus-host disease

Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21− B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21− B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27−CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21− B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21− B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21− B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21−CD27−CD10− B cell frequencies as a biomarker of disease severity

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies

Advanced topics supplement PSSC physics : Uri Haber-Schaim, John H Dodge, James A. Walter

202 p. : il.; 27 cm

Evaluating the effects of oseltamivir phosphate on platelet counts: a retrospective review

Desialylation of platelets results in platelet clearance by the Ashwell-Morrell Receptors (AMR) found on hepatocytes. Studies suggest that oseltamivir phosphate inhibits human sialidases, enzymes responsible for desialylation, extending the lifespan of circulating platelets. We thus evaluated, the effects of oseltamivir on platelet count (PC) following treatment. Of the 385 patients evaluated for influenza, 283 (73.5%) were influenza-infected. Of the 283 infected patients, 241 (85.2%) received oseltamivir (I + O+) while 42 patients did not (I + O-). One hundred two non-infected patients received oseltamivir (I-O+). The two groups receiving oseltamivir (I + O+, I-O+), demonstrated a statistically greater increase in the PC (57.53 ± 93.81, p = .013 and 50.79 ± 70.59, p = .023, respectively) relative to the group that did not (18.45 ± 89.33 × 109/L). The observed increase in PC was statistically similar (p = .61) in both groups receiving oseltamivir (I + O+, I-O+), suggesting that this effect is independent of influenza. Comparing clinical characteristics between responders and non-responders to oseltamivir treatment showed that only duration of oseltamivir treatment (AOR = 1.30, 95% CI 1.05–1.61, p = .015) was associated with a positive PC response. Our findings suggest a correlation between oseltamivir treatment and an increase in PCs. Future studies assessing the possible uses of oseltamivir in medical conditions characterized by diminished or defective thrombopoiesis are warranted