Performance study of the ablative Z-pinch pulsed plasma thruster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76691/1/AIAA-2001-3898-280.pd

The impact of prior platinum therapy on survival in patients with metastatic urothelial cancer receiving vinflunine

Background: A phase III trial demonstrated an overall survival advantage with the addition of vinflunine to best supportive care (BSC) in platinum-refractory advanced urothelial cancer. We subsequently examined the impact of an additional 2 years of survival follow-up and evaluated the influence of first-line platinum therapy on survival. Methods: The 357 eligible patients from the phase III study were categorised into two cohorts depending on prior cisplatin treatment: cisplatin or non-cisplatin. Survival was calculated using the Kaplan–Meier method. Results: The majority had received prior cisplatin (70.3%). Survival was higher in the cisplatin group (HR: 0.76; CI 95% 0.58–0.99; P=0.04) irrespective of treatment arm. Multivariate analysis including known prognostic factors (liver involvement, haemoglobin, performance status) and prior platinum administration did not show an independent effect of cisplatin. Vinflunine reduced the risk of death by 24% in the cisplatin-group (HR: 0.76; CI 95% 0.58–0.99; P=0.04) and by 35% in non-cisplatin patients (HR: 0.65; CI 95% 0.41–1.04; P=0.07). Interpretation: Differences in prognostic factors between patients who can receive prior cisplatin and those who cannot may explain the survival differences in patients who undergo second line therapy. Prior cisplatin administration did not diminish the subsequent benefit of vinflunine over BSC

'Candidatus Phytoplasma phoenicium’ associated with almond witches’-broom disease: from draft genome to genetic diversity among strain populations

BACKGROUND: Almond witches'-broom (AlmWB), a devastating disease of almond, peach and nectarine in Lebanon, is associated with 'Candidatus Phytoplasma phoenicium'. In the present study, we generated a draft genome sequence of 'Ca. P. phoenicium' strain SA213, representative of phytoplasma strain populations from different host plants, and determined the genetic diversity among phytoplasma strain populations by phylogenetic analyses of 16S rRNA, groEL, tufB and inmp gene sequences. RESULTS: Sequence-based typing and phylogenetic analysis of the gene inmp, coding an integral membrane protein, distinguished AlmWB-associated phytoplasma strains originating from diverse host plants, whereas their 16S rRNA, tufB and groEL genes shared 100 % sequence identity. Moreover, dN/dS analysis indicated positive selection acting on inmp gene. Additionally, the analysis of 'Ca. P. phoenicium' draft genome revealed the presence of integral membrane proteins and effector-like proteins and potential candidates for interaction with hosts. One of the integral membrane proteins was predicted as BI-1, an inhibitor of apoptosis-promoting Bax factor. Bioinformatics analyses revealed the presence of putative BI-1 in draft and complete genomes of other 'Ca. Phytoplasma' species. CONCLUSION: The genetic diversity within 'Ca. P. phoenicium' strain populations in Lebanon suggested that AlmWB disease could be associated with phytoplasma strains derived from the adaptation of an original strain to diverse hosts. Moreover, the identification of a putative inhibitor of apoptosis-promoting Bax factor (BI-1) in 'Ca. P. phoenicium' draft genome and within genomes of other 'Ca. Phytoplasma' species suggested its potential role as a phytoplasma fitness-increasing factor by modification of the host-defense response

One Dimensional Hybrid-Vlasov Simulation of a Hall Thruster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97103/1/AIAA2012-4313.pd

Ablative Z-Pinch Pulsed Plasma Thruster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77148/1/AIAA-4362-652.pd

Vector assembly of colloids on monolayer substrates

The key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize 'vector assembly' by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers

Association of immunotherapy and immunosuppression with severe COVID-19 disease in patients with cancer

Background: Cytokine storm due to COVID-19 can cause high morbidity and mortality. Patients with cancer treated with immunotherapy (IO) and those with immunosuppression may have higher rates of cytokine storm due to immune dysregulation. We sought to evaluate the association of IO and immunosuppression with COVID-19 outcomes and cytokine storm occurrence among patients with cancer and COVID-19, based on data from the COVID-19 and Cancer Consortium (CCC19). Methods: A registry-based retrospective cohort study was conducted on patients reported to the CCC19 registry from March 2020 to September 2021. The primary outcome was defined as an ordinal scale of COVID-19 severity. The secondary outcome was the occurrence of a cytokine storm using CCC19 variables, defined as biological and clinical evidence of severe inflammation, with end-organ dysfunction (Fajgenbaum D.C. et al., N Engl J Med., 2020). The association of IO or immunosuppression with the outcomes of interest were evaluated using a multivariable logistic regression balanced for covariate distributions through inverse probability of treatment weighting (IPTW). Results: A total of 10,214 patients were included, among which 482 (4.7%) received IO, 3,715 (36.4%) received non-IO systemic therapies, and 6,017 (58.9%) were untreated in the 3 months prior to COVID-19 diagnosis. No difference in COVID-19 severity or the development of a cytokine storm was found in the IO group compared to the untreated group (aOR: 0.77; 95%CI:0.45-1.32, and aOR: 1.06; 95%CI:0.42-2.67, respectively). On multivariable analysis, baseline immunosuppression was associated with worse outcomes both in relation to COVID-19 severity (aOR: 1.89; 95%CI:1.51-2.35) and the presence of a cytokine storm (aOR: 1.75; 95%CI:1.30-2.35). Conclusions: Administration of IO was not associated with severe outcomes in patients with cancer and COVID-19, whereas pre-existing baseline immunosuppression appears to be independently associated with worse clinical outcomes including cytokine storm

Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial.

BACKGROUND: Progression-free survival was significantly longer in patients who received avelumab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma (aRCC) in a randomized phase III trial. We report long-term safety and efficacy of avelumab plus axitinib as first-line treatment for patients with aRCC from the JAVELIN Renal 100 phase Ib trial (NCT02493751). MATERIALS AND METHODS: In this open-label, multicenter, phase Ib study, patients with untreated aRCC received avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily or with axitinib for 7 days followed by avelumab plus axitinib. Safety and efficacy were assessed in all patients receiving at least one dose of avelumab or axitinib. RESULTS: Overall, 55 patients were enrolled and treated. Median follow-up was 55.7 months (95% CI, 54.5-58.7). Treatment-related adverse events of any grade or grade ≥3 occurred in 54 (98.2%) and 34 (61.8%) patients, respectively. The confirmed objective response rate was 60.0% (95% CI, 45.9-73.0), including complete response in 10.9% of patients. Median duration of response was 35.9 months (95% CI, 12.7-52.9); the probability of response was 65.8% (95% CI, 46.7-79.4) at 2 years. Median progression-free survival was 8.3 months (95% CI, 5.3-32.0). Median overall survival was not reached (95% CI, 40.8-not estimable); the 5-year overall survival rate was 57.3% (95% CI, 41.2-70.5). CONCLUSION: Five-year follow-up for combination treatment with avelumab plus axitinib in previously untreated patients with aRCC showed long-term clinical activity with no new safety signals, supporting use of this regimen within its approved indication in clinical practice (Clinicaltrials.gov NCT02493751)

Plasma Characterization of Hall Thruster with Active and Passive Segmented Electrodes

Non-emissive electrodes and ceramic spacers placed along the Hall thruster channel are shown to affect the plasma potential distribution and the thruster operation. These effects are associated with physical properties of the electrode material and depend on the electrode configuration, geometry and the magnetic field distribution. An emissive segmented electrode was able to maintain thruster operation by supplying an additional electron flux to sustain the plasma discharge between the anode and cathode neutralizer. These results indicate the possibility of new configurations for segmented electrode Hall thruster

MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential ‘Achilles’ heel’ of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases