We propose using table-top-size ultra-stable optical cavities from state-of-the-art optical atomic clocks as bar gravitational wave detectors for frequencies higher than 2 kHz. We show that the 2-20 ...kHz range of gravitational waves' spectrum can be accessed with instruments below 2 meters in size. The materials and properties of the proposed cavities are in the grasp of today's technology. The ultra-stable optical cavities allow detection not only predicted gravitational wave signals from such sources as binary neutron star mergers and post-mergers, subsolar-mass primordial black-hole mergers, and collapsing stellar cores, but can also reach new physics beyond the standard model, looking for ultralight bosons such as QCD axions and axion-like particles formed through black hole superradiance.
Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16−, intermediate ...CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Current knowledge on human monocyte heterogeneity is still incomplete: while it is increasingly acknowledged that CD14++CD16+ monocytes are of outstanding significance in 2 global health issues, namely HIV-1 infection and atherosclerosis, CD14++CD16+ monocytes remain the most poorly characterized subset so far. We therefore developed a method to purify the 3 monocyte subsets from human blood and analyzed their transcriptomes using SuperSAGE in combination with high-throughput sequencing. Analysis of 5 487 603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the 2 other monocyte subsets. Gene Ontology (GO) enrichment analysis suggests diverse immunologic functions, linking CD14++CD16+ monocytes to Ag processing and presentation (eg, CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (eg, TGFB1, AIF1, PTPN6), and to angiogenesis (eg, TIE2, CD105). In conclusion, we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. After CD14++CD16+ monocytes have earlier been discussed as a potential therapeutic target in inflammatory diseases, we are hopeful that our data will spur further research in the field of monocyte heterogeneity.
Objectives The aim of this study was to analyze the yet ill-defined relationship of distinct human monocyte subsets with cardiovascular outcomes in a broad patient population at cardiovascular risk. ...Background Monocytes, the most abundant immune cell type found in atherosclerotic plaques, are crucial promoters of atherogenesis. Three distinct human monocyte subsets exist: classical CD14++CD16−, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Immunomodulation of distinct monocyte subsets has recently been discussed as a new therapeutic avenue in atherosclerosis. Methods Cardiovascular events in 951 subjects referred for elective coronary angiography were prospectively analyzed. Monocyte subset analysis was performed using flow cytometry, blinded to patients' clinical characteristics, and patients were categorized according to quartiles of total monocyte and monocyte subset counts. The primary endpoint was defined a priori as the first occurrence of cardiovascular death, acute myocardial infarction, or nonhemorrhagic stroke. Endpoint adjudication was done blinded to monocyte subset distribution. Results During a mean follow-up period of 2.6 ± 1.0 years, 93 patients experienced the primary endpoint. In univariate Kaplan-Meier analysis, counts of total (p = 0.010), classical CD14++CD16− (p = 0.024), and intermediate CD14++CD16+ (p < 0.001) monocytes predicted the primary endpoint, whereas nonclassical monocytes did not (p = 0.158). After full adjustment for confounders, CD14++CD16+ monocytes remained the only monocyte subset independently related to cardiovascular events (fourth vs. first quartile: hazard ratio: 3.019; 95% confidence interval: 1.315 to 6.928; p = 0.009). Conclusions CD14++CD16+ monocytes independently predicted cardiovascular events in subjects referred for elective coronary angiography. Future studies will be needed to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies in atherosclerosis.
Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface ...marker 6-sulfo LacNAc (slan) can define slan-positive CD14+CD16++ nonclassical monocytes and slan-negative CD14++CD16+ intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c+ dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings.
•The slan marker can be used to define nonclassical and intermediate monocytes in human blood.•slan-negative intermediate monocytes are expanded in sarcoidosis, and slan-positive nonclassical monocytes are depleted in HDLS.
We report on the first Earth-scale quantum sensor network based on optical atomic clocks aimed at dark matter (DM) detection. Exploiting differences in the susceptibilities to the fine-structure ...constant of essential parts of an optical atomic clock, i.e., the cold atoms and the optical reference cavity, we can perform sensitive searches for DM signatures without the need for real-time comparisons of the clocks. We report a two orders of magnitude improvement in constraints on transient variations of the fine-structure constant, which considerably improves the detection limit for the standard model (SM)-DM coupling. We use Yb and Sr optical atomic clocks at four laboratories on three continents to search for both topological defect and massive scalar field candidates. No signal consistent with a DM coupling is identified, leading to considerably improved constraints on the DM-SM couplings.
Superradiant active clocks operating on narrow linewidth clock transitions are predicted to achieve precision orders of magnitude higher than any currently existing optical atomic clocks. We ...introduce a theory of superradiant lasing and implement it for the example of
Ca atoms. The presented model, however, is valid for any two- or three-level system in an optical lattice. We perform a feasibility analysis and suggest a set of parameters for the experimental fulfillment of superradiant lasing in Ca. Moreover, we present an overview of different magic wavelengths for the 4s
S
↔ 4s4p
P
(m
= 0) transition in Ca for different polarizations and a robustness analysis of these magic conditions. We also report the magic-zero wavelengths for the 4s4p
P
, m
= 0 state.
Progress in realizing the SI second had multiple technological impacts and enabled further constraint of theoretical models in fundamental physics. Caesium microwave fountains, realizing best the ...second according to its current definition with a relative uncertainty of 2-4 × 10(-16), have already been overtaken by atomic clocks referenced to an optical transition, which are both more stable and more accurate. Here we present an important step in the direction of a possible new definition of the second. Our system of five clocks connects with an unprecedented consistency the optical and the microwave worlds. For the first time, two state-of-the-art strontium optical lattice clocks are proven to agree within their accuracy budget, with a total uncertainty of 1.5 × 10(-16). Their comparison with three independent caesium fountains shows a degree of accuracy now only limited by the best realizations of the microwave-defined second, at the level of 3.1 × 10(-16).
It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their ...dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates.
We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011-16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient).
Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of -0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators.
This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.
Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been ...associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF).
We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models.
Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 Q1:0;Q3:16000 IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 Q1:0;Q3:16000 vs 8000 Q1:0;Q3:20000 IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687).
Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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