Efficient coupling to an optical resonator by exploiting time-reversal symmetry

The interaction of a cavity with an external field is symmetric under time reversal. Thus, coupling to a resonator is most efficient when the incident light is the time reversed version of a free cavity decay, i.e. when it has a rising exponential shape matching the cavity lifetime. For light entering the cavity from only one side, the maximally achievable coupling efficiency is limited by the choice of the cavity mirrors' reflectivities. Such an empty-cavity experiment serves also as a model system for single-photon single-atom absorption dynamics. We present experiments coupling exponentially rising pulses to a cavity system which allows for high coupling efficiencies. The influence of the time constant of the rising exponential is investigated as well as the effect of a finite pulse duration. We demonstrate coupling 94% of the incident TEM00 mode into the resonator.Comment: 7 pages, 5 figure

Allogeneic Stem Cell Transplantation From HLA-Mismatched Donors for Pediatric Patients with Acute Lymphoblastic Leukemia Treated According to the 2003 BFM and 2007 International-BFM Studies: Impact of Disease Risk on Outcomes.

Summary Rational Allogeneic HSCT is beneficial for pediatric patients with relapsed or (very) high-risk ALL in remission. A total of 1115 consecutive patients were included in the ALL SCT 2003 BFM study and the ALL SCT 2007-International study and were stratified according to relapse risk (Standard vs. High vs. Very High Risk of Relapse) and donor type (Matched Sibling vs. Matched Donor vs. Mismatched Donor). Patients and methods A total of 148 patients (60% male, median age 8.7 years; B-cell precursor ALL: 75%) were transplanted from MMD, which was defined as either less than 9/10 HLA-compatible donors or less than 5/6 unrelated cord blood after myelo-ablative conditioning regimen (TBI-based: 67%) for HRR (n=42) or VHRR disease (n=106). The stem cell source was either BM (n=31), unmanipulated PBSCs (n=28), T-cell ex vivo depleted PBSCs (n=59) or cord blood (n=25). The median follow-up was 5.1 years. Results The 4-year OS and EFS was 56±4% and 52±4%, respectively, for the entire cohort. Patients transplanted from MMD for HRR disease obtained remarkable 4-y OS and EFS values of 82±6% and 80±6%, respectively, while VHRR patients obtained values of 45±5% and 42±5% (p Conclusion HSCT with a mismatched donor is feasible in pediatric ALL patients but leads to inferior results compared to HSCT with better matched donors, at least for patients transplanted for VHRR. The results are strongly affected by disease status. The main cause of treatment failure is still relapse, highlighting the urgent need for interventional strategies after HSCT for patients with residual leukemia before and/or after transplantatio

The impact of donor type on the outcome of pediatric patients with very high risk acute lymphoblastic leukemia. A study of the ALL SCT 2003 BFM-SG and 2007-BFM-International SG

Allogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01–11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p < 0.001) for the whole cohort. This difference does not exist if considering separately patients treated in the most recent study. There was no difference in 4-year CI of relapse. The 4-year NRM was lower for patients transplanted from MD (9 ± 1% vs. 23 ± 4%, p < 0.001). In multivariate analysis, donor-type appears as a negative risk-factor for OS, EFS, and NRM. This paper demonstrates the impact of donor type on overall results of allogeneic stem cell transplantation for very-high risk pediatric acute lymphoblastic leukemia with worse results when using MMD stem cell source

Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation : Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.Peer reviewe

Two phases of disulfide bond formation have differing requirements for oxygen

Most proteins destined for the extracellular space require disulfide bonds for folding and stability. Disulfide bonds are introduced co- and post-translationally in endoplasmic reticulum (ER) cargo in a redox relay that requires a terminal electron acceptor. Oxygen can serve as the electron acceptor in vitro, but its role in vivo remains unknown. Hypoxia causes ER stress, suggesting a role for oxygen in protein folding. Here we demonstrate the existence of two phases of disulfide bond formation in living mammalian cells, with differential requirements for oxygen. Disulfide. bonds introduced rapidly during protein synthesis can occur without oxygen, whereas those introduced during post-translational folding or isomerization are oxygen dependent. Other protein maturation processes in the secretory pathway, including ER-localized N-linked glycosylation, glycan trimming, Golgi-localized complex glycosylation, and protein transport, occur independently of oxygen availability. These results suggest that an alternative electron acceptor is available transiently during an initial phase of disulfide bond formation and that post-translational oxygen-dependent disulfide bond formation causes hypoxia-induced ER stress

Optimizing free-space light-matter interaction by mode matching

This thesis describes an experiment to optimize the interaction of light and a single ion in free space. The key to efficient coupling consists in mode-matching the incident electromagnetic field to the radiative properties of the ion. For perfect coupling, the incident mode has to match the emission pattern of the ion. In free space, this requires illumination of the ion with an incoming dipole wave. In the present work, such a situation is realized experimentally. To this end, a radially polarized doughnut mode is focused with a deep parabolic mirror while the ion is localized in the focal point of the parabolic mirror by means of a trap of special geometry. This thesis reports first on the implementation of the two basic components of the experiment: the ion trapping in the focal point of the parabolic mirror and the generation of the required doughnut mode. Then, the coupling efficiency of the combined system is analyzed by means of saturation measurements. Characterization of our setup reveals aberrations of the parabolic mirror which prevent perfect coupling. However, the measured coupling efficiency of (7.2 ± 0.2)% is to date among the highest values reported for coupling experiments with a single atom in free space. A special aim of our group is the full excitation of an ion by a single photon. This requires, in addition to the above mentioned spatial mode matching, temporal shaping of the incident light. Perfect excitation can be achieved if the single-photon wavepacket shows an exponentially rising envelope with a time constant matching the lifetime of the excited state of the ion. The present work demonstrates the power of temporal mode matching using a model system: an empty optical cavity. Both, light inside a cavity and atomic excitation, decay exponentially. Thus, there is an analogy between atomic excitation and field energy inside a cavity. The task of exciting an ion translates to the task of coupling a classical light pulse into a cavity. This thesis confirms experimentally that almost the entire energy of a rising exponential pulse can be coupled into a cavity, provided the pulse time constant matches the cavity lifetime.Die vorliegende Arbeit beschreibt ein Experiment, in dem die Wechselwirkung zwischen Licht und einem einzelnen Ion im freien Raum maximiert wird. Der Schlüssel zu effizienter Kopplung liegt dabei in der Anpassung des eingestrahlten elektromagnetischen Feldes an die Strahlungseigenschaften des Ions: Für perfekte Kopplung muss die einfallende Lichtmode mit dem Emissionsmuster des Ions übereinstimmen. Eine solche Situation wird für ein Ion im freien Raum durch Beleuchtung mit einer einlaufenden Dipolwelle erreicht. Dies wird in der vorliegenden Arbeit experimentell realisiert, indem eine radial polarisierte Donut-Mode von einem tiefen Parabolspiegel fokussiert wird. Das Ion wird dabei mit Hilfe einer speziell konfigurierten Falle im Fokus des Parabolspiegels festgehalten. Diese Dissertation beschreibt zunächst die Inbetriebnahme der Apparatur zum Fangen eines einzelnen Ions im Fokus des Parabolspiegels sowie die Erzeugung der notwendigen Donut-Mode. Anschließend werden Kopplungsexperimente in Form von Sättigungsmessungen präsentiert. Die Charakterisierung unseres Aufbaus deckt Aberrationen unseres Parabolspiegels auf, die eine perfekte Kopplung verhindern. Die erzielte Kopplungseffizienz von (7, 2 ± 0, 2)% zählt zu den höchsten Effizienzen, die mit einem einzelnen Atom im freien Raum bislang erreicht wurden. Ein besonderes Ziel unserer Arbeitsgruppe ist die vollständige Anregung eines einzelnen Ions durch ein einzelnes Photon. Dies benötigt zusätzlich zur oben beschriebenen räumlichen Moden-Anpassung eine Berücksichtigung des zeitlichen Freiheitsgrades. Vollständige Anregung kann erreicht werden, wenn das einfallende Einzelphotonen-Wellenpaket eine exponentiell ansteigende Einhüllende aufweist. Die Zeitkonstante muss dabei mit der Lebensdauer des angeregten atomaren Zustands übereinstimmen. Dieses Konzept der zeitlichen Moden-Anpassung wird im Rahmen dieser Dissertation an einem Modell-System demonstriert: ein leerer optischer Resonator. Da sowohl die atomare Anregung als auch die Feld-Energie im Resonator einem exponentiellen Zerfallsgesetz folgen, besteht eine Analogie zwischen den beiden Systemen. Das Analogon zu einem Anregungsexperiment ist dabei der Versuch, einen Laserpuls in den Resonator einzukoppeln. In der vorliegenden Arbeit wird experimentell bestätigt, dass eine nahezu vollständige Einkopplung möglich ist, wenn der Puls eine exponentiell ansteigende Einhüllende aufweist. Die Zeitkonstante des Pulses muss dabei mit der Lebensdauer des Resonators übereinstimmen