Nanopore device and a method for nucleic acid analysis

A nanopore device is described wherein is provided a sample input (110), an input chamber (120), and first and second sample chambers (130, 140) connected to the input chambers (120) via first and second nanopores (135, 145)

Extended polarized semiclassical model for quantum-dot cavity QED and its application to single-photon sources

We present a simple extension of the semi-classical model for a two-level system in a cavity, in order to incorporate multiple polarized transitions, such as those appearing in neutral and charged quantum dots (QDs), and two nondegenerate linearly polarized cavity modes. We verify the model by exact quantum master equation calculations, and experimentally using a neutral QD in a polarization non-degenerate micro-cavity, in both cases we observe excellent agreement. Finally, the usefulness of this approach is demonstrated by optimizing a single-photon source based on polarization postselection, where we find an increase in the brightness for optimal polarization conditions as predicted by the model.Comment: 8 pages, for simple code see https://doi.org/10.5281/zenodo.347666

Multiple Myeloma Relapse Is Associated with Increased NFκB Pathway Activity and Upregulation of the Pro-Survival BCL-2 Protein BFL-1

Multiple myeloma (MM) is a hematological malignancy that is still considered incurable due to the development of therapy resistance and subsequent relapse of disease. MM plasma cells (PC) use NFκB signaling to stimulate cell growth and disease progression, and for protection against therapy-induced apoptosis. Amongst its diverse array of target genes, NFκB regulates the expression of pro-survival BCL-2 proteins BCL-XL, BFL-1, and BCL-2. A possible role for BFL-1 in MM is controversial, since BFL-1, encoded by BCL2A1, is downregulated when mature B cells differentiate into antibody-secreting PC. NFκB signaling can be activated by many factors in the bone marrow microenvironment and/or induced by genetic lesions in MM PC. We used the novel signal transduction pathway activity (STA) computational model to quantify the functional NFκB pathway output in primary MM PC from diverse patient subsets at multiple stages of disease. We found that NFκB pathway activity is not altered during disease development, is irrespective of patient prognosis, and does not predict therapy outcome. However, disease relapse after treatment resulted in increased NFκB pathway activity in surviving MM PC, which correlated with increased BCL2A1 expression in a subset of patients. This suggests that BFL-1 upregulation, in addition to BCL-XL and BCL-2, may render MM PC resistant to therapy-induced apoptosis, and that BFL-1 targeting could provide a new approach to reduce therapy resistance in a subset of relapsed/refractory MM patients

ER and PI3K pathway activity in primary ER positive breast cancer is associated with progression-free survival of metastatic patients under first-line tamoxifen

Estrogen receptor positive (ER+) breast cancer patients are eligible for hormonal treatment, but only around half respond. A test with higher specificity for prediction of endocrine therapy response is needed to avoid hormonal overtreatment and to enable selection of alternative treatments. A novel testing method was reported before that enables measurement of functional signal transduction pathway activity in individual cancer tissue samples, using mRNA levels of target genes of the respective pathway-specific transcription factor. Using this method, 130 primary breast cancer samples were analyzed from non-metastatic ER+ patients, treated with surgery without adjuvant hormonal therapy, who subsequently developed metastatic disease that was treated with first-line tamoxifen. Quantitative activity levels were measured of androgen and estrogen receptor (AR and ER), PI3K-FOXO, Hedgehog (HH), NFκB, TGFβ, and Wnt pathways. Based on samples with known pathway activity, thresholds were set to distinguish low from high activity. Subsequently, pathway activity levels were correlated with the tamoxifen treatment response and progression-free survival. High ER pathway activity was measured in 41% of the primary tumors and was associated with longer time to progression (PFS) of metastases during first-line tamoxifen treatment. In contrast, high PI3K, HH, and androgen receptor pathway activity was associated with shorter PFS, and high PI3K and TGFβ pathway activity with worse treatment response. Potential clinical utility of assessment of ER pathway activity lies in predicting response to hormonal therapy, while activity of PI3K, HH, TGFβ, and AR pathways may indicate failure to respond, but also opens new avenues for alternative or complementary targeted treatments

Mapping a 50-spin-qubit network through correlated sensing

Spins associated to optically accessible solid-state defects have emerged as a versatile platform for exploring quantum simulation, quantum sensing and quantum communication. Pioneering experiments have shown the sensing, imaging, and control of multiple nuclear spins surrounding a single electron-spin defect. However, the accessible size and complexity of these spin networks has been constrained by the spectral resolution of current methods. Here, we map a network of 50 coupled spins through high-resolution correlated sensing schemes, using a single nitrogen-vacancy center in diamond. We develop concatenated double-resonance sequences that identify spin-chains through the network. These chains reveal the characteristic spin frequencies and their interconnections with high spectral resolution, and can be fused together to map out the network. Our results provide new opportunities for quantum simulations by increasing the number of available spin qubits. Additionally, our methods might find applications in nano-scale imaging of complex spin systems external to the host crystal.Comment: 7 pages, 5 figure