Single-photon-level narrowband memory in a hollow-core photonic bandgap fiber.

An experimental platform operating at the level of individual quanta and providing strong light-matter coupling is a key requirement for quantum information processing. In our work, we show that hollow-core photonic bandgap fibers filled with laser-cooled atoms might serve as such a platform, despite their typical complicated birefringence properties. To this end, we present a detailed theoretical and experimental study to identify a fiber with suitable properties to achieve operation at the single-photon level. In the fiber, we demonstrate the storage and on-demand retrieval as well as the creation of stationary light pulses, based on electromagnetically induced transparency, for weak coherent light pulses down to the single-photon level with an unconditional noise floor of 0.017(4) photons per pulse. These results clearly demonstrate the prospects of such a fiber-based platform for applications in quantum information networks.

Accounting for multiple ecosystem services in a simulation of land-use decisions: Does it reduce tropical deforestation?

Conversion of tropical forests is among the primary causes of global environmental change. The loss of their important environmental services has prompted calls to integrate ecosystem services (ES) in addition to socio-economic objectives in decision-making. To test the effect of accounting for both ES and socio-economic objectives in land-use decisions, we develop a new dynamic approach to model deforestation scenarios for tropical mountain forests. We integrate multi-objective optimization of land allocation with an innovative approach to consider uncertainty spaces for each objective. These uncertainty spaces account for potential variability among decision-makers, who may have different expectations about the future. When optimizing only socio-economic objectives, the model continues the past trend in deforestation (1975-2015) in the projected land-use allocation (2015-2070). Based on indicators for biomass production, carbon storage, climate and water regulation, and soil quality, we show that considering multiple ES in addition to the socio-economic objectives has heterogeneous effects on land-use allocation. It saves some natural forest if the natural forest share is below 38%, and can stop deforestation once the natural forest share drops below 10%. For landscapes with high shares of forest (38%-80% in our study), accounting for multiple ES under high uncertainty of their indicators may, however, accelerate deforestation. For such multifunctional landscapes, two main effects prevail: (a) accelerated expansion of diversified non-natural areas to elevate the levels of the indicators and (b) increased landscape diversification to maintain multiple ES, reducing the proportion of natural forest. Only when accounting for vascular plant species richness as an explicit objective in the optimization, deforestation was consistently reduced. Aiming for multifunctional landscapes may therefore conflict with the aim of reducing deforestation, which we can quantify here for the first time. Our findings are relevant for identifying types of landscapes where this conflict may arise and to better align respective policies.

The Impact of Integrin ß2 on Granulocyte/Macrophage Progenitor Proliferation.

Previously, we reported that although the HSPC frequency in bone marrow cells (BMC) was comparable between ß2-/- and ß2+/+ mice, transplantation of ß2-/- BMC into lethally irradiated CD45.1 recipient resulted in more myeloid cell production than ß2+/+ BMC. The objective of this study is to address if integrin ß2 deficiency skews granulocyte/macrophage progenitor (GMP) proliferation. FACS analysis demonstrated that GMP frequency and cell number were higher and megakaryocyte/erythrocyte progenitor frequency and cell number were lower in ß2-/- mice than ß2+/+ mice. However, the common myeloid progenitors (CMP) frequency and cell number were similar between the two groups. The increased GMP number was due to GMP proliferation as evidenced by the percentage of BrdU-incorporating GMP. Whole genome transcriptome analysis identified increased FcεRIα expression in ß2-/- CMP compared to ß2+/+ CMP. FcεRIα expression on ß2-/- GMP was detected increased in ß2-/- mice by qRT-PCR and FACS. Although transplantation of FcεRIαhi GMP or FcεRIαlo GMP into lethally irradiated CD45.1 recipient resulted in comparable myeloid cell production, transplantation of ß2 deficient FcεRIαhi GMP generated more myeloid cells than ß2+/+ FcεRIαhi GMP. GATA2 expression was increased in ß2-/- GMP. Using a luciferase reporter assay, we demonstrated that mutation of the GATA2 binding site in the FcεRIα promoter region diminished FcεRIα transcription. In vitro, the addition of IgE, the ligand of FcεRIα, promoted GMP expansion, which was abrogated by inhibition of JNK phosphorylation. Integrin ß2 deficiency promoted GMP proliferation and myeloid cell production, which was mediated via FcεRIα/IgE-induced JNK phosphorylation in GMP. Stem Cells 2019;37:430-440.

S1-Guidelines on UV phototherapy and photochemotherapy.

Known in part since antiquity, the salutary effects of sunlight again garnered increasing attention in the second half of the 19(th) century. The development of a device for ultraviolet irradiation of cutaneous tuberculosis by Finnsen at the onset of the twentieth century truly marked the beginning of modern phototherapy. In dermatology, treatment methods almost exclusively use wavelengths below the visible light range (ultraviolet light). Since the early 1970s, increasingly powerful artificial light sources have become available for UVB and UVA therapy as well as the combination of UVA and photosensitizers (photochemotherapy). High structural and procedural quality standards are an essential prerequisite for the implementation of effective as well as safe phototherapy. The following guidelines outline the current consensus of leading experts in the field of phototherapy with respect to indications, contraindications, and side effects of various treatment options available. Particular focus is also on adequate UV doses at the beginning and over the further course of treatment as well as on management of side effects.

S1-Leitlinie zur UV-Phototherapie und Photochemotherapie.

Die heilsame Wirkung des Sonnenlichts war teilweise schon im Altertum bekannt und fand in der zweiten Hälfte des 19. Jahrhunderts wieder zunehmend Beachtung. Den Beginn der modernen Phototherapien markiert die Entwicklung einer Apparatur zur ultravioletten Bestrahlung der Hauttuberkulose durch Finnsen zu Beginn des zwanzigsten Jahrhunderts. Zur Therapie von Hauterkrankungen finden beinahe ausschließlich die spektralen Bereiche unterhalb des sichtbaren Lichtes (ultraviolett) Anwendung. Seit den 1970er Jahren stehen zunehmend leistungsfähige künstliche Strahlenquellen bereit für die Therapie mit UVB, UVA und die Kombination von UVA mit Photosensibilisatoren (Photochemotherapie). Hohe strukturelle und prozedurale Qualitätsstandards sind unabdingbare Voraussetzung für die Durchführung einer gleichermaßen wirkungsvollen wie auch sicheren Phototherapie. Die Leitlinie formuliert den aktuellen Konsens führender Experten auf dem Gebiet der Phototherapie in Bezug auf die Indikationen für die jeweiligen Therapieverfahren, deren Gegenanzeigen und Nebenwirkungen und insbesondere für die Wahl der korrekten Dosis zu Beginn und im Verlauf einer Therapie sowie das Management von Nebenwirkungen.

Hematopoietic stem/progenitor cells directly contribute to arteriosclerotic progression via integrin ß2.

Recent studies described the association between hematopoietic stem/progenitor cell (HSPC) expansion in the bone marrow (BM), leukocytosis in the peripheral blood, and accelerated atherosclerosis. We hypothesized that circulating HSPC may home to inflamed vessels, where they might contribute to inflammation and neointima formation. We demonstrated that Lin(-) Sca-1(+) cKit(+) (LSK cells) in BM and peripheral blood of LDLr(-/-) mice on high fat diet expressed significantly more integrin ß2 , which was responsible for LSK cell adhesion and migration toward ICAM-1 in vitro, and homing to injured arteries in vivo, all of which were blocked with an anti-CD18 blocking antibody. When homed LSK cells were isolated from ligated artery and injected to irradiated recipients, they resulted in BM reconstitution. Injection of CD18(+/+) LSK cells to immunodeficient Balb/C Rag2(-) É£C(-/-) recipients resulted in more severe inflammation and reinforced neointima formation in the ligated carotid artery, compared to mice injected with PBS and CD18(-/-) LSK cells. Hypercholesterolemia stimulated ERK phosphorylation (pERK) in LSK cells of LDLr(-/-) mice in vivo. Blockade of pERK reduced ARF1 expression, leading to decreased integrin ß2 function on HSPC. In addition, integrin ß2 function could be regulated via ERK-independent LRP1 pathway. Integrin ß2 expression on HSPC is regulated by hypercholesterolemia, specifically LDL, in pERK-dependent and -independent manners, leading to increased homing and localization of HSPC to injured arteries, which is highly correlated with arteriosclerosis.

An ecological paradox: high species diversity and low position of the upper forest line in the Andean Depression.

Systematic investigations of the upper forest line (UFL) primarily concentrate on mid and high latitudes of the Northern Hemisphere, whereas studies of Neotropical UFLs are still fragmentary. This article outlines the extraordinary high tree diversity at the UFL within the Andean Depression and unravels the links between the comparatively low position of the local UFL, high tree-species diversity, and climate. On the basis of Gentry's rapid inventory methodology for the tropics, vegetation sampling was conducted at 12 UFL sites, and local climate (temperature, wind, precipitation, and soil moisture) was investigated at six sites. Monotypic forests dominated by Polylepis were only found at the higher located margins of the Andean Depression while the lower situated core areas were characterized by a species-rich forest, which lacked the elsewhere dominant tree-species Polylepis. In total, a remarkably high tree-species number of 255 tree species of 40 different plant families was found. Beta-diversity was also high with more than two complete species turnovers. A non-linear relationship between the floristic similarity of the investigated study sites and elevation was detected. Temperatures at the investigated study sites clearly exceeded 5.5°C, the postulated threshold value for the upper tree growth limit in the tropics. Instead, quasi-permanent trade winds, high precipitation amounts, and high soil water contents affect the local position of the UFL in a negative way. Interestingly, most of the above-mentioned factors are also contributing to the high species richness. The result is a combination of a clearly marked upper forest line depression combined with an extraordinary forest line complexity, which was an almost unknown paradox.

ß2 integrin mediates hantavirus-induced release of neutrophil extracellular traps.

Rodent-borne hantaviruses are emerging human pathogens that cause severe human disease. The underlying mechanisms are not well understood, as hantaviruses replicate in endothelial and epithelial cells without causing any cytopathic effect. We demonstrate that hantaviruses strongly stimulated neutrophils to release neutrophil extracellular traps (NETs). Hantavirus infection induced high systemic levels of circulating NETs in patients and this systemic NET overflow was accompanied by production of autoantibodies to nuclear antigens. Analysis of the responsible mechanism using neutrophils from ß2 null mice identified ß2 integrin receptors as a master switch for NET induction. Further experiments suggested that ß2 integrin receptors such as complement receptor 3 (CR3) and 4 (CR4) may act as novel hantavirus entry receptors. Using adenoviruses, we confirmed that viral interaction with ß2 integrin induced strong NET formation. Collectively, ß2 integrin-mediated systemic NET overflow is a novel viral mechanism of immunopathology that may be responsible for characteristic aspects of hantavirus-associated disease such as kidney and lung damage.

One-dimensional ultracold medium of extreme optical depth.

We report on the preparation of a one-dimensional ultracold medium in a hollow-core photonic crystal fiber, reaching an effective optical depth of 1000(150). We achieved this extreme optical depth by transferring atoms from a magneto-optical trap into a far-detuned optical dipole trap inside the hollow-core fiber, yielding up to 2.5(3)×10(5) atoms inside the core with a loading efficiency of 2.5(6)%. The preparation of an ultracold medium of such huge optical depth paves the way toward new applications in quantum optics and nonlinear optics.

Reduction of CD18 promotes expansion of inflammatory γδ T cells collaborating with CD4+ T cells in chronic murine psoriasiform dermatitis.

IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of γδ T cells, accounting for an important source of IL-17 in acute murine IL-23- and imiquimod-induced skin inflammation, in human psoriasis is still unclear. Using the polygenic CD18(hypo) PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/ß2 integrin expression to 2-16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory γδ T cells and analyzed the occurrence of IL-17-producing γδ and CD4(+) T cells at different disease stages. Severity of CD18(hypo) PL/J psoriasiform dermatitis correlated with a loss of skin-resident Vγ5(+) T cells and concurrent skin infiltration with IL-17(+), IL-22(+), and TNF-α(+) γδTCR(low) cells preceded by increases in Vγ4(+) T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type γδ T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18(hypo) PL/J mice with anti-γδTCR Abs significantly reduced skin inflammation and largely eliminated pathological γδ and CD4(+) T cells. Moreover, CD18(hypo) γδ T cells induced allogeneic CD4(+) T cell responses more potently than CD18(wt) counterparts and, upon adoptive transfer, triggered psoriasiform dermatitis in susceptible hosts. These results demonstrate a novel function of reduced CD18 levels in generation of pathological γδ T cells that was confirmed by detection of increases in CD18(low) γδ T cells in psoriasis patients and may also have implications for other inflammatory diseases.

Reduced CD18 levels drive regulatory T cell conversion into Th17 cells in the CD18hypo PL/J mouse model of psoriasis.

Defective development and function of CD4(+)CD25(high+)Foxp3(+) regulatory T cells (Tregs) contribute to the pathogenesis of psoriasis and other autoimmune diseases. Little is known about the influence of adhesions molecules on the differentiation of Foxp3(+) Tregs into proinflammatory Th17 cells occurring in lesional skin and blood of psoriasis patients. In the CD18(hypo) PL/J mouse model of psoriasis, reduced expression of CD18/ß2 integrin to 2-16% of wild-type levels is associated with progressive loss of Tregs, impaired cell-cell contact between Tregs and dendritic cells (DCs), as well as Treg dysfunction as reported earlier. In the present investigation, Tregs derived from CD18(hypo) PL/J mice were analyzed for their propensity to differentiate into IL-17-producing Th17 cells in vivo and in in vitro Treg-DC cocultures. Adoptively transferred CD18(hypo) PL/J Tregs were more inclined toward conversion into IL-17-producing Th17 cells in vivo in an inflammatory as well as noninflammatory environment compared with CD18(wt) PL/J Tregs. Addition of neutralizing Ab against CD18 to Treg-DC cocultures in vitro promoted conversion of CD18(wt) PL/J Tregs to Th17 cells in a dose-dependent manner similar to conversion rates of CD18(hypo) PL/J Tregs. Reduced thymic output of naturally occurring Tregs and peripheral conversion of Tregs into Th17 cells therefore both contribute to the loss of Tregs and the psoriasiform dermatitis observed in CD18(hypo) PL/J mice. Our data overall indicate that CD18 expression levels impact Treg development as well as Treg plasticity and that differentiation of Tregs into IL-17-producing Th17 cells is distinctly facilitated by a subtotal deficiency of CD18.

Variable ultrabroadband and narrowband composite polarization retarders.

We propose and experimentally demonstrate novel types of composite sequences of half-wave and quarter-wave polarization retarders, permitting operation at either ultrabroad spectral bandwidth or narrow bandwidth. The retarders are composed of stacked standard half-wave retarders and quarter-wave retarders of equal thickness. To our knowledge, these home-built devices outperform all commercially available compound retarders, made of several birefringent materials.

Highly efficient broadband conversion of light polarization by composite retarders.

Driving on an analogy with the technique of composite pulses in quantum physics, we propose highly efficient broadband polarization converters composed of sequences of ordinary retarders rotated at specific angles with respect to their fast-polarization axes.

Adaptive immune response to model antigens is impaired in murine leukocyte-adhesion deficiency-1 revealing elevated activation thresholds in vivo.

Absence of ß2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of ß2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of ß2 integrin-deficiency (CD18⁻/⁻). CD18⁻/⁻ mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18⁻/⁻ mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18⁻/⁻ mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.

An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice.

Uncontrolled macrophage activation is now considered to be a critical event in the pathogenesis of chronic inflammatory diseases such as atherosclerosis, multiple sclerosis, and chronic venous leg ulcers. However, it is still unclear which environmental cues induce persistent activation of macrophages in vivo and how macrophage-derived effector molecules maintain chronic inflammation and affect resident fibroblasts essential for tissue homeostasis and repair. We used a complementary approach studying human subjects with chronic venous leg ulcers, a model disease for macrophage-driven chronic inflammation, while establishing a mouse model closely reflecting its pathogenesis. Here, we have shown that iron overloading of macrophages--as was found to occur in human chronic venous leg ulcers and the mouse model--induced a macrophage population in situ with an unrestrained proinflammatory M1 activation state. Via enhanced TNF-α and hydroxyl radical release, this macrophage population perpetuated inflammation and induced a p16(INK4a)-dependent senescence program in resident fibroblasts, eventually leading to impaired wound healing. This study provides insight into the role of what we believe to be a previously undescribed iron-induced macrophage population in vivo. Targeting this population may hold promise for the development of novel therapies for chronic inflammatory diseases such as chronic venous leg ulcers.

Observation of phase variation within stationary light pulses inside a cold atomic medium.

The successful formation of stationary light pulses in a cold atomic medium was demonstrated recently. However, unlike in hot media, a detuning between the counterpropagating fields had to be applied. Here we demonstrate that a significant nonuniform phase variation can be induced during a period of stationary light owing to off-resonantly driven transitions. The experimental results are in good agreement with theoretical predictions for media of low optical depth. For media of high optical depth the numerical simulations indicate that such phase variation becomes negligible. Thus stationary light based on this coupling scheme could be used for possible future applications in quantum information processing.