Adiabatic two-qubit gates in capacitively coupled quantum dot hybrid qubits

The ability to tune qubits to flat points in their energy dispersions ("sweet spots") is an important tool for mitigating the effects of charge noise and dephasing in solid-state devices. However, the number of derivatives that must be simultaneously set to zero grows exponentially with the number of coupled qubits, making the task untenable for as few as two qubits. This is a particular problem for adiabatic gates, due to their slower speeds. Here, we propose an adiabatic two-qubit gate for quantum dot hybrid qubits, based on the tunable, electrostatic coupling between distinct charge configurations. We confirm the absence of a conventional sweet spot, but show that controlled-Z (CZ) gates can nonetheless be optimized to have fidelities of $\sim$99% for a typical level of quasistatic charge noise ($\sigma_\varepsilon$$\simeq$1 $\mu$eV). We then develop the concept of a dynamical sweet spot (DSS), for which the time-averaged energy derivatives are set to zero, and identify a simple pulse sequence that achieves an approximate DSS for a CZ gate, with a 5$\times$ improvement in the fidelity. We observe that the results depend on the number of tunable parameters in the pulse sequence, and speculate that a more elaborate sequence could potentially attain a true DSS.Comment: 14 pages, 9 figure

In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

BACKGROUND: Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression. METHODS: In specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro. RESULTS: Patients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown. CONCLUSIONS: We could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC

Impact of Blood Loss on Renal Function and Interaction with Ischemia Duration after Nephron-Sparing Surgery

Objectives: Nephron-sparing surgery (NSS) exposes the kidney to ischemia–reperfusion injury. Blood loss and hypotension are also associated with kidney injury. We aimed to test the hypothesis that, during NSS, both ischemia duration and blood loss significantly affect postoperative renal function and that their effects interact. Methods: Consecutive patients undergoing NSS were enrolled. The primary endpoint was renal function expressed as the absolute delta between preoperative and postoperative peak creatinine. We developed a generalized linear model with the ischemia duration and absolute hemoglobin difference as independent variables, their interaction term, and the RENAL score. The model was than expanded to include a history of hypertension (as a proxy for hypotension susceptibility) and related interaction terms. Further, we described the perioperative and mid-term oncological outcomes. Results: A total of 478 patients underwent NSS, and 209 (43.7%) required ischemia for a mean of 10.9 min (SD 8). Both the ischemia duration (partial eta 0.842, p = 0.006) and hemoglobin difference (partial eta 0.933, p = 0.029) significantly affected postoperative renal function, albeit without evidence of a significant interaction (p = 0.525). The RENAL score also significantly influenced postoperative renal function (p = 0.023). After the addition of a previous history of hypertension, the effects persisted, with a significant interaction between blood loss and a history of hypertension (p = 0.02). Conclusions: Ischemia duration and blood loss had a similar impact on postoperative renal function, albeit without potentiating each other. While the surgical technique and ischemia minimization remain crucial to postoperative kidney function, increased awareness of conscious hemodynamic management appears warranted

Cellular Adaptation to VEGF-Targeted Antiangiogenic Therapy Induces Evasive Resistance by Overproduction of Alternative Endothelial Cell Growth Factors in Renal Cell Carcinoma

AbstractVascular endothelial growth factor (VEGF)–targeted antiangiogenic therapy significantly inhibits the growth of clear cell renal cell carcinoma (RCC). Eventually, therapy resistance develops in even the most responsive cases, but the mechanisms of resistance remain unclear. Herein, we developed two tumor models derived from an RCC cell line by conditioning the parental cells to two different stresses caused by VEGF-targeted therapy (sunitinib exposure and hypoxia) to investigate the mechanism of resistance to such therapy in RCC. Sunitinib-conditioned Caki-1 cells in vitro did not show resistance to sunitinib compared with parental cells, but when tested in vivo, these cells appeared to be highly resistant to sunitinib treatment. Hypoxia-conditioned Caki-1 cells are more resistant to hypoxia and have increased vascularity due to the upregulation of VEGF production; however, they did not develop sunitinib resistance either in vitro or in vivo. Human endothelial cells were more proliferative and showed increased tube formation in conditioned media from sunitinib-conditioned Caki-1 cells compared with parental cells. Gene expression profiling using RNA microarrays revealed that several genes related to tissue development and remodeling, including the development and migration of endothelial cells, were upregulated in sunitinib-conditioned Caki-1 cells compared with parental and hypoxia-conditioned cells. These findings suggest that evasive resistance to VEGF-targeted therapy is acquired by activation of VEGF-independent angiogenesis pathways induced through interactions with VEGF-targeted drugs, but not by hypoxia. These results emphasize that increased inhibition of tumor angiogenesis is required to delay the development of resistance to antiangiogenic therapy and maintain the therapeutic response in RCC

Global change of surgical and oncological clinical practice in urology during early COVID-19 pandemic

Objectives!#!While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic.!##!Methods!#!In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated.!##!Results!#!235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21-24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02).!##!Conclusion!#!The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic

Additional file 3: of In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

Figure S3. Human phospho-kinase array (Roche) of transfected 786-O and A498 cells. Protein extracts were obtained from PTEN-Δ and PTEN transfected cells and analyzed concerning the phosphorylation status of 46 intracellular signaling kinases. The activity of the kinases AKT, JNK and p38 are highlighted with red boxes. (PDF 111 kb