A high-flux BEC source for mobile atom interferometers

Quantum sensors based on coherent matter-waves are precise measurement devices whose ultimate accuracy is achieved with Bose-Einstein condensates (BEC) in extended free fall. This is ideally realized in microgravity environments such as drop towers, ballistic rockets and space platforms. However, the transition from lab-based BEC machines to robust and mobile sources with comparable performance is a challenging endeavor. Here we report on the realization of a miniaturized setup, generating a flux of $4 \times 10^5$ quantum degenerate $^{87}$Rb atoms every 1.6$\,$s. Ensembles of $1 \times 10^5$ atoms can be produced at a 1$\,$Hz rate. This is achieved by loading a cold atomic beam directly into a multi-layer atom chip that is designed for efficient transfer from laser-cooled to magnetically trapped clouds. The attained flux of degenerate atoms is on par with current lab-based BEC experiments while offering significantly higher repetition rates. Additionally, the flux is approaching those of current interferometers employing Raman-type velocity selection of laser-cooled atoms. The compact and robust design allows for mobile operation in a variety of demanding environments and paves the way for transportable high-precision quantum sensors.Comment: 22 pages, 6 figure

Coherent terabit communications with microresonator Kerr frequency combs

Optical frequency combs enable coherent data transmission on hundreds of wavelength channels and have the potential to revolutionize terabit communications. Generation of Kerr combs in nonlinear integrated microcavities represents a particularly promising option enabling line spacings of tens of GHz, compliant with wavelength-division multiplexing (WDM) grids. However, Kerr combs may exhibit strong phase noise and multiplet spectral lines, and this has made high-speed data transmission impossible up to now. Recent work has shown that systematic adjustment of pump conditions enables low phase-noise Kerr combs with singlet spectral lines. Here we demonstrate that Kerr combs are suited for coherent data transmission with advanced modulation formats that pose stringent requirements on the spectral purity of the optical source. In a first experiment, we encode a data stream of 392 Gbit/s on subsequent lines of a Kerr comb using quadrature phase shift keying (QPSK) and 16-state quadrature amplitude modulation (16QAM). A second experiment shows feedback-stabilization of a Kerr comb and transmission of a 1.44 Tbit/s data stream over a distance of up to 300 km. The results demonstrate that Kerr combs can meet the highly demanding requirements of multi-terabit/s coherent communications and thus offer a solution towards chip-scale terabit/s transceivers

iSense: a technology platform for cold atom based quantum technologies

A breakthrough in cold atom quantum technology is hindered by a bottleneck in the supporting technologies. We discuss a cold atom technology platform developed within the European iSense project, aiming at a gravimeter as demonstrator

Successful Treatment of Early Relapsed High-Risk AML After Allogeneic Hematopoietic Stem Cell Transplantation With Biomodulatory Therapy

Early relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an often unsuccessful therapeutic challenge. Since treatment options are few and efficacy is low, new approaches such as de novo allo-HSCT, targeted therapies and biomodulatory drugs have been developed, albeit prognosis is very poor. In this manuscript we present an unusual case of a patient with high-risk AML with an unbalanced jumping translocation and FLT3-TKD (low) mutation who presented with early relapse (FLT3 negative) after allo-HSCT, refractory to one cycle of azacytidine and discontinuation of immunosuppression (IS). As salvage therapy, the patient received a biomodulatory therapy consisting of low-dose azacytidine 75 mg/day (given s.c. d1-7 of 28), pioglitazone 45 mg/day orally, and all-trans-retinoic acid (ATRA) 45 mg/m(2)/day orally achieving a complete remission after two cycles of therapy. Even after cessation of treatment after 5 cycles, the patient remained in complete remission with full chimerism in peripheral blood and bone marrow for another 7 months. In conclusion, we report about an unusual case of long-lasting complete remission of early relapsed high-risk AML after allo-HSCT treated with azacytidine, pioglitazone and ATRA after standard of care treatment with HMA and discontinuation of IS failed

Welche Chancen bietet die Immunonkologie für ein indikationsübergreifendes Langzeitüberleben?

Tumore nutzen verschiedene Escape-Mechanismen, um das körpereigene Immunsystem zu überlisten und sich gegenüber der Tumor-Immunabwehr durchzusetzen: Die Erkenntnis, dass sie immunregulative Moleküle wie z.B. CTLA-4 (Cytotoxic T Lymphocyte Antigen 4) oder PD-1 (programmed cell death 1) sowie deren Liganden PD-L1/PD-L2 instrumentalisieren können, um der Immunüberwachung zu entkommen (immune escape), hat einen vollständig neuen Therapiezugang für die Onkologie eröffnet..

Biomodulatory Treatment With Azacitidine, All-trans Retinoic Acid and Pioglitazone Induces Differentiation of Primary AML Blasts Into Neutrophil Like Cells Capable of ROS Production and Phagocytosis

Effective and tolerable salvage therapies for elderly patients with chemorefractory acute myeloid leukemia (AML) are limited and usually do not change the poor clinical outcome. We recently described in several chemorefractory elderly AML patients that a novel biomodulatory treatment regimen consisting of low-dose azacitidine (AZA) in combination with PPARγ agonist pioglitazone (PGZ) and all-trans retinoic acid (ATRA) induced complete remission of leukemia and also triggered myeloid differentiation with rapid increase of peripheral blood neutrophils. Herein, we further investigated our observations and comprehensively analyzed cell differentiation in primary AML blasts after treatment with ATRA, AZA, and PGZ ex vivo. The drug combination was found to significantly inhibit cell growth as well as to induce cell differentiation in about half of primary AML blasts samples independent of leukemia subtype. Notably and in comparison to ATRA/AZA/PGZ triple-treatment, effects on cell growth and myeloid differentiation with ATRA monotherapy was much less efficient. Morphological signs of myeloid cell differentiation were further confirmed on a functional basis by demonstrating increased production of reactive oxygen species as well as enhanced phagocytic activity in AML blasts treated with ATRA/AZA/PGZ. In conclusion, we show that biomodulatory treatment with ATRA/AZA/PGZ can induce phenotypical and functional differentiation of primary AML blasts into neutrophil like cells, which aside from its antileukemic activity may lower neutropenia associated infection rates in elderly AML patients in vivo. Clinical impact of the ATRA/AZA/PGZ treatment regimen is currently further investigated in a randomized clinical trial in chemorefractory AML patients (NCT02942758)

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

Welche Chancen bietet die Immunonkologie für ein indikationsübergreifendes Langzeitüberleben?

Therapeutische Einsatzmöglichkeiten von Immun-Checkpoint-Inhibitoren. Immunonkologie beim NSCLC - aktuelle Perspektiven. Immunonkologie beim RCC - ein Revival mit Durchbruch? Immunonkologie in der Hämatologie - integrierte Therapiekonzepte für nachhaltige Tumortherapie

STE-QUEST - Test of the Universality of Free Fall Using Cold Atom Interferometry

In this paper, we report about the results of the phase A mission study of the atom interferometer instrument covering the description of the main payload elements, the atomic source concept, and the systematic error sources

IRF4 downregulation improves sensitivity and endurance of CAR T cell functional capacities

Chimeric antigen receptor (CAR) modified T cells can induce complete remissions in patients with advanced hematological malignancies. Nevertheless, the efficacy is mostly transient and remains so far poor in the treatment of solid tumors. Crucial barriers to long-term CAR T cell success encompass loss of functional capacities known as “exhaustion”, among others. To extend CAR T cell functionality, we reduced interferon regulatory factor 4 (IRF4) levels in CAR T cells using a one-vector system encoding a specific short-hairpin (sh) RNA along with constitutive CAR expression. At baseline, CAR T cells with downregulated IRF4 showed equal cytotoxicity and cytokine release compared to conventional CAR T cells. However, under conditions of repetitive antigen encounter, IRF4low CAR T cells displayed enhanced functionality with superior cancer cell control in the long-term compared with conventional CAR T cells. Mechanistically, the downregulation of IRF4 in CAR T cells resulted in prolonged functional capacities and upregulation of CD27. Moreover, IRF4low CAR T cells were more sensitive to cancer cells with low levels of target antigen. Overall, IRF4 downregulation capacitates CAR T cells to recognize and respond to target cells with improved sensitivity and endurance