Coherent and robust high-fidelity generation of a biexciton in a quantum dot by rapid adiabatic passage

A biexciton in a semiconductor quantum dot is a source of polarization-entangled photons with high potential for implementation in scalable systems. Several approaches for non-resonant, resonant and quasi-resonant biexciton preparation exist, but all have their own disadvantages, for instance low fidelity, timing jitter, incoherence or sensitivity to experimental parameters. We demonstrate a coherent and robust technique to generate a biexciton in an InGaAs quantum dot with a fidelity close to one. The main concept is the application of rapid adiabatic passage to the ground state-exciton-biexciton system. We reinforce our experimental results with simulations which include a microscopic coupling to phonons.Comment: Main manuscript 5 pages and 4 figures, Supplementary Information 5 pages and 3 figures, accepted as a Rapid Communication in PRB. arXiv admin note: text overlap with arXiv:1701.0130

Demonstrating the decoupling regime of the electron-phonon interaction in a quantum dot using chirped optical excitation

Excitation of a semiconductor quantum dot with a chirped laser pulse allows excitons to be created by rapid adiabatic passage. In quantum dots this process can be greatly hindered by the coupling to phonons. Here we add a high chirp rate to ultra-short laser pulses and use these pulses to excite a single quantum dot. We demonstrate that we enter a regime where the exciton-phonon coupling is effective for small pulse areas, while for higher pulse areas a decoupling of the exciton from the phonons occurs. We thus discover a reappearance of rapid adiabatic passage, in analogy to the predicted reappearance of Rabi rotations at high pulse areas. The measured results are in good agreement with theoretical calculations.Comment: Main manuscript 5 pages and 4 figures, Supplementary Information 5 pages and 3 figures, submitted to PR

Optically driving the radiative Auger transition

In a radiative Auger process, optical decay is accompanied by simultaneous excitation of other carriers. The radiative Auger process gives rise to weak red-shifted satellite peaks in the optical emission spectrum. These satellite peaks have been observed over a large spectral range: in the X-ray emission of atoms; close to visible frequencies on donors in semiconductors and quantum emitters; and at infrared frequencies as shake-up lines in two-dimensional systems. So far, all the work on the radiative Auger process has focussed on detecting the spontaneous emission. However, the fact that the radiative Auger process leads to photon emission suggests that the transition can also be optically excited. In such an inverted radiative Auger process, excitation would correspond to simultaneous photon absorption and electronic de-excitation. Here, we demonstrate optical driving of the radiative Auger transition on a trion in a semiconductor quantum dot. The radiative Auger and the fundamental transition together form a $\Lambda$-system. On driving both transitions of this $\Lambda$-system simultaneously, we observe a reduction of the fluorescence signal by up to $70\%$. Our results demonstrate a type of optically addressable transition connecting few-body Coulomb interactions to quantum optics. The results open up the possibility of carrying out THz spectroscopy on single quantum emitters with all the benefits of optics: coherent laser sources, efficient and fast single-photon detectors. In analogy to optical control of an electron spin, the $\Lambda$-system between the radiative Auger and the fundamental transitions allows optical control of the emitters' orbital degree of freedom.Comment: 8 pages, 6 figure

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Sorafenib versus lenvatinib-based sequential systemic therapy for advanced hepatocellular carcinoma: a real-world analysis

The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were included. Child B cirrhosis was present in 26 patients (16.5%), whereas 132 patients (83.5%) had preserved liver function. In total, 72 patients (44%) discontinued systemic therapy after first-line therapy while 51 (31%) and 31 (19%) patients received 2 or more treatment lines. Most notably, median overall survival (mOS) was influenced by liver functional status and patient performance status at the beginning of first-line therapy. Patients receiving a sequential therapy regimen had significantly longer mOS compared to patients that discontinued systemic therapy after omitting first-line treatment. The choice of the initial TKI did not impact mOS. A clear deterioration of liver function could be observed during the course of TKI-based treatment

Changes of basic bone turnover parameters in short-term and long-term patients with spinal cord injury

The bone mineral density (BMD), the cross- links (PYD, DPD and NTx) and the bone specific alcaline phosphatase (BAP) was investigated in a cross-sectional study in 62 male patients with spinal cord injury (SCI), n = 28 short-term (0–1 year after SCI) and n = 34 long-term SCI patients (> 5 years after SCI). Knowledge about this parameters are necessary to find an adequate therapy for this special kind of osteoporosis. Immobilisation osteoporosis in SCI patients is a well-known problem that may lead to pathological fractures. Little is known regarding the extend of the osteoporosis as well as the causative factors. Measurements of the BMD in the proximal femur and the lumbar spine were performed with dual-energy-X-ray-absorptiometry (DEXA), of the osteoblast marker BAP (bone specific alkaline phosphatase) from serum and the osteoclast markers PYD (pyridinoline), DPD (desoxy-pyridinoline) and NTx (N-telopeptide of collagen type I) from urine. We found a significant decrease of BMD in the proximal femur and no relevant change in the lumbar spine compared to an age- and sex correlated control group (Z-score) in short-term and long-term SCI patients. There was a significant bone loss at the proximal femur between short and long-term SCI patients, whereas at the lumbar spine the BMD even slightly increases. Bone resorption (cross-links) was increased in both groups, though in long-term SCI patients it is significantly decreased compared to short-term SCI patients (DPD from 211.7 u/g creatinine to 118.1 u/g creatinine; NTx from 215.1 nmol/mmol creatinine to 83,6 nmol/mmol creatinine). The bone formation marker BAP is slightly below normal range in both groups (12.3 U/l in short-term, 9.7 U/l in long- term SCI patients). Only the proximal femur is affected by the immobilisation osteoporosis of SCI patients, therefore the BMD measurements in these patients should be performed at the lower limb. The problem of the immobilisation osteoporosis in SCI patients is the striking increase of bone resorption and the missing reaction of the bone formation

Diagnostic scheme for the HITRAP decelerator

The HITRAP linear decelerator currently being set up at GSI will provide slow, few keV/u highly charged ions for atomic physics experiments. The expected beam intensity is up to 105 ions per shot. To optimize phase and amplitude of the RF systems intensity, bunch length and kinetic energy of the particles need to be monitored. The bunch length that we need to fit is about 2 ns, which is typically measured by capacitive pickups. However, they do not work for the low beam intensities that we face. We investigated the bunch length with a fast CVD diamond detector working in single particle counting mode. Averaging over 8 shots yields a clear, regular picture of the bunched beam. Energy measurements by capacitive pickups are limited by the presence of intense primary and partially decelerated beam and hence make tuning of the IH-structure impossible. The energy of the decelerated fraction of the beam behind the first deceleration cavity was determined to about 10 % accuracy with a permanent dipole magnet combined with a MCP. Better detector calibration should help reaching the required 1%. Design of the detectors as well as the results of the measurements will be presented