Why material slow light does not improve cavity-enhanced atom detection

We discuss the prospects for enhancing absorption and scattering of light from a weakly coupled atom in a high-finesse optical cavity by adding a medium with large, positive group index of refraction. The slow-light effect is known to narrow the cavity transmission spectrum and increase the photon lifetime, but the quality factor of the cavity may not be increased in a metrologically useful sense. Specifically, detection of the weakly coupled atom through either cavity ringdown measurements or the Purcell effect fails to improve with the addition of material slow light. A single-atom model of the dispersive medium helps elucidate why this is the case.Comment: 11 pages, 4 figures; QuTiP python file included. This version: changed title and added several references; results are unchanged. Accepted for open access publication in a special issue of Journal of Modern Optics in memory of Prof Danny Segal. Publisher's version available at http://dx.doi.org/10.1080/09500340.2017.138451

Directional bistability and nonreciprocal lasing with cold atoms in a ring cavity

We demonstrate lasing into counter-propagating modes of a ring cavity using a gas of cold atoms as a gain medium. The laser operates under the usual conditions of magneto-optical trapping with no additional fields. We characterize the threshold behavior of the laser and measure the second-order optical coherence. The laser emission exhibits directional bistability, switching randomly between clockwise and counter-clockwise modes, and a tuneable nonreciprocity is observed as the atoms are displaced along the cavity axis.Comment: Authors' version, with supplemental material included. Published in PRL at https://doi.org/10.1103/PhysRevLett.121.16360

Late Pleistocene paleosol formation in a dynamic aggradational microenvironment - A case study from the Malá nad Hronom loess succession (Slovakia)

The geomorphological characteristics of the loess succession at Malá nad Hronom (Slovakia) mean that it provides a valuable opportunity for the investigation of differences in soil formation in various topographic positions. Along with the semiquantitative characterization of the paleosols (on the basis of physical properties, texture, the characteristics of peds, clay films, horizon boundaries), high-resolution field magnetic susceptibility measurements and sampling were carried out along four different sections of the profile. Samples for luminescence dating were also taken, in order to establish the chronostratigraphical position of the paleosols studied. The comparison of various proxies revealed the differences in soil formation in a dynamic aggradational microenvironment for the same paleosol horizons located in various positions along the slope. Contrary to expectation, paleosols developed in local top or slope topographical positions did not display significant differences in e.g. in their degree of development, nor the characteristics of their magnetic susceptibility curves. In the case of paleosols in positions lower down the slope, signs of quasi-permanent sediment input could be recognized as being present as early as during the formation of the soil itself. This sediment input would seem to be surpassed in the case of pedogenesis strengthened by the climate of the last interglacial (marine isotope stage - MIS 5). Pedogenesis seems to be sustained by renewed intense dust accumulation in the Late Pleistocene, in MIS 3, though compared to MIS 5, the climate of MIS 3 did not favor intense pedogenesis. Despite the general belief that loess series formed in plateau positions can preserve terrestrial records without significant erosion, in the case of the Malá nad Hronom loess this is not so. Compared to the sequence affected by erosional events in the local top position, the sequence affected by quasi-continuous sediment input in the lower slope position seems to have preserved the soil horizons intact.International Visegrad Fund (project Number 11410020). The paper was also supported by a long-term conceptual development subvention available to research organizations RVO: 68145535 from the Institute of Geonics AS CR, by the Slovak Research and Development Agency under contract No. APVV-0625-11 (project “A new synthesis of the Western Carpathians landform evolution – preparation of the database for testing of key hypotheses”. B. Bradák acknowledges the financial support of project BU235P18 (Junta de Castilla y Leon, Spain) and the European Regional Development Fund (ERD), project PID2019-108753GB-C21 / AECI / 10.13039/501100011033 of the Agencia Estatal de Investigación and project PID2019-105796GB-100 / AECI / 10.13039/501100011033 of the Agencia Estatal de Investigación

Cytomolecular identification of individual wheat-wheat chromosome arm associations in wheat-rye hybrids

Chromosome pairing in the meiotic metaphase I of wheatrye hybrids has been characterized by sequential genomic and fluorescent in situ hybridization allowing not only the discrimination of wheat and rye chromosomes, but also the identification of the individual wheat and rye chromosome arms involved in the chromosome associations. The majority of associations (93.8%) were observed between the wheat chromosomes. The largest number of wheat-wheat chromosome associations (53%) was detected between the A and D genomes, while the frequency of B-D and A-B associations was significantly lower (32 and 8%, respectively). Among the A-D chromosome associations, pairing between the 3AL and 3DL arms was observed with the highest frequency, while the most frequent of all the chromosome associations (0.113/ cell) was found to be the 3DS-3BS. Differences in the pairing frequency of the individual chromosome arms of wheat-rye hybrids have been discussed in relation to the homoeologous relationships between the constituent genomes of hexaploid wheat

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

MASP-1 Induces a Unique Cytokine Pattern in Endothelial Cells: A Novel Link between Complement System and Neutrophil Granulocytes

Microbial infection urges prompt intervention by the immune system. The complement cascade and neutrophil granulocytes are the predominant contributors to this immediate anti-microbial action. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), the most abundant enzyme of the complement lectin pathway, can induce p38-MAPK activation, NFkappaB signaling, and Ca(2+)-mobilization in endothelial cells. Since neutrophil chemotaxis and transmigration depends on endothelial cell activation, we aimed to explore whether recombinant MASP-1 (rMASP-1) is able to induce cytokine production and subsequent neutrophil chemotaxis in human umbilical vein endothelial cells (HUVEC). We found that HUVECs activated by rMASP-1 secreted IL-6 and IL-8, but not IL-1alpha, IL-1ra, TNFalpha and MCP-1. rMASP-1 induced dose-dependent IL-6 and IL-8 production with different kinetics. rMASP-1 triggered IL-6 and IL-8 production was regulated predominantly by the p38-MAPK pathway. Moreover, the supernatant of rMASP-1-stimulated HUVECs activated the chemotaxis of neutrophil granulocytes as an integrated effect of cytokine production. Our results implicate that besides initializing the complement lectin pathway, MASP-1 may activate neutrophils indirectly, via the endothelial cells, which link these effective antimicrobial host defense mechanisms

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

Cleavage of Kininogen and Subsequent Bradykinin Release by the Complement Component: Mannose-Binding Lectin-Associated Serine Protease (MASP)-1

Bradykinin (BK), generated from high-molecular-weight kininogen (HK) is the major mediator of swelling attacks in hereditary angioedema (HAE), a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×102 and 2.7×102 M−1s−1, respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients

A novel human skin chamber model to study wound infection ex vivo

Wound infections with multi-drug resistant bacteria increase morbidity and mortality and have considerable socioeconomic impact. They can lead to impaired wound healing, resulting in rising treatment costs. The aim of this study was to investigate an ex vivo human wound infection model. Human full-thickness skin from the operating room (OR) was placed into the Bo-Drum® and cultivated for 7 days in an air–liquid interphase. On day 8, the skin was inoculated with either (1) Pseudomonas aeruginosa, (2) Staphylococcus aureus (105 CFU, n = 3) or (3) carrier control. 1, 3 and 7 days after inoculation colony forming units in the tissue/media were determined and cytokine expression was quantified. A reliable and reproducible wound infection could be established for 7 days. At this timepoint, 1.8 × 108 CFU/g tissue of P. aeruginosa and 2 × 107 CFU/g tissue of S. aureus were detected. Immunohistochemical analysis demonstrated bacterial infection and epidermolysis in infected skin. RT-PCR analysis exhibited a significant induction of proinflammatory cytokines after infection. The BO-drum® is a robust, easy-to-use, sterilizable and reusable ex vivo full-skin culture system. For investigation of wound infection, treatment and healing, the BO-drum® presents a convenient model and may help to standardize wound research