Parallel entangling operations on a universal ion-trap quantum computer.

The circuit model of a quantum computer consists of sequences of gate operations between quantum bits (qubits), drawn from a universal family of discrete operations1. The ability to execute parallel entangling quantum gates offers efficiency gains in numerous quantum circuits2-4, as well as for entire algorithms-such as Shor's factoring algorithm5-and quantum simulations6,7. In circuits such as full adders and multiple-control Toffoli gates, parallelism can provide an exponential improvement in overall execution time through the divide-and-conquer technique8. More importantly, quantum gate parallelism is essential for fault-tolerant error correction of qubits that suffer from idle errors9,10. However, the implementation of parallel quantum gates is complicated by potential crosstalk, especially between qubits that are fully connected by a common-mode bus, such as in Coulomb-coupled trapped atomic ions11,12 or cavity-coupled superconducting transmons13. Here we present experimental results for parallel two-qubit entangling gates in an array of fully connected trapped 171Yb+ ion qubits. We perform a one-bit full-addition operation on a quantum computer using a depth-four quantum circuit4,14,15, where circuit depth denotes the number of runtime steps required. Our method exploits the power of highly connected qubit systems using classical control techniques and will help to speed up quantum circuits and achieve fault tolerance in trapped-ion quantum computers.

Decrease in tumor cell contamination and progenitor cell yield in leukapheresis products after consecutive cycles of chemotherapy for breast cancer treatment.

In this retrospective study, we assessed the impact of each of three consecutive cycles of conventional-dose chemotherapy on CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and contaminating breast cancer cells collected in the leukapheresis products of patients with metastatic breast cancer. The patients subsequently underwent high-dose chemotherapy followed by autologous blood progenitor cell transplantation. We analyzed 172 leukapheresis products from 17 patients and have correlated the long-term clinical outcome with tumor cell contamination. The induction chemotherapy regimen consisted of three cycles of cyclophosphamide 750 mg/m2 i.v., epirubicin 100 mg/m2, and 5-fluorouracil (5-FU) 750 mg/m2 i.v., followed by 5 microg/kg body weight of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) daily until leukapheresis was completed. An average of 10 leukapheresis products (three to four collections after each cycle of chemotherapy) were obtained from each patient. Numbers of CD34+ cells, CFU-GM, and mononuclear cells (MNCs) in the leukapheresis products were determined at the time of collection. Aliquots from the same products were frozen and breast cancer cells were detected by immunocytochemistry with a cocktail of anti-cytokeratin antibodies (AE-1, AE-3, CAM 5.2, Keratin 8+18+19) using a standardized immunoalkaline phosphatase method. A minimum of 10(6) cells were examined by light microscopy and by at least two blinded observers. Cells were considered positive when immunostaining was detected in the cytoplasm and on the cell membrane, and cellular morphology was consistent with a malignant phenotype. Of the 172 samples analyzed, 13 of 57 (23%) leukapheresis products collected after cycle I were positive for tumor cells; 3 of 60 (5%) after cycle II; and 4 of 55 (7%) after cycle III. The likelihood of contamination by breast cancer cells after cycle I was significantly higher than after subsequent cycles of chemotherapy (p = 0.0052). Simultaneously, there was a significant decrease in quantity of CD34+ cells and CFU-GM (p < 0.0001 for both comparisons). Our study indicated that leukapheresis products collected after the second or third cycles of induction chemotherapy carry a significantly lower likelihood of tumor cell contamination, albeit the quantity of CD34+ cells or CFU-GM collected was also significantly reduced.

Use of a tumor-cell enrichment column for the enhanced detection of minimal residual disease in the BM or apheresis peripheral blood transplant products of breast-cancer patients.

BACKGROUND: Contaminating tumor cells present in the BM or apheresis peripheral blood (APB) autologous transplant products have been shown to contribute to relapse following high-dose chemotherapy and stem-cell rescue (HDC/ASCR). Enhanced methods for tumor detection in BM or APB products for breast-cancer patients are required. METHODS: We evaluated a laboratory-scale tumor-cell enrichment column (TEC) as an enhanced method of detecting tumor cells in APB or BM of breast-cancer patients. Seventeen women with breast cancer (14 Stage IV and three Stage III) were evaluated using the TEC for residual tumor cells present in 20 samples of APB or BM biopsies following HDC/ASCR. RESULTS: Using conventional histological staining methods (without TEC), only one patient had evidence of tumor cells present in the BM biopsy, while 16 patients had negative biopsies. Using the TEC for tumor cell capture and immunocytochemical (ICC) staining with anti-cytokeratin MAb (CAM 5.2) for tumor detection, we were able to positively identify tumor cells in 20 samples (14 BM aspirates and six APB products). In 15 samples (nine BM and six APB), we used CAM 5.2 to positively identify cytokeratin(+) cells prior to using the TEC. However, positive cells were detected only after using the TEC in the remaining five samples. The level of sensitivity was significantly enhanced (p < or = 0.05) by 100-400 fold in the post-TEC (absorbed) fraction compared with the pre-TEC (post-Ficoll) fraction. DISCUSSION: We conclude from this study that the use of TEC improves our ability to detect residual breast-cancer cells in the APB or BM and could be potentially utilized to purge contaminating tumor cells from the stem-cell transplant.