NMR implementation of Quantum Delayed-Choice Experiment

We report the first experimental demonstration of quantum delayed-choice experiment via nuclear magnetic resonance techniques. An ensemble of molecules each with two spin-1/2 nuclei are used as target and the ancilla qubits to perform the quantum circuit corresponding the delayed-choice setup. As expected in theory, our experiments clearly demonstrate the continuous morphing of the target qubit between particle-like and wave-like behaviors. The experimental visibility of the interference patterns shows good agreement with the theory.Comment: Revised text, more figures adde

Contrasting effects of sleep fragmentation and angiotensin-II treatment upon pro-inflammatory responses of mice

Disordered sleep promotes inflammation in brain and peripheral tissues, but the mechanisms that regulate these responses are poorly understood. One hypothesis is that activation of the sympathetic nervous system (SNS) from sleep loss elevates blood pressure to promote vascular sheer stress leading to inflammation. As catecholamines produced from SNS activation can directly regulate inflammation, we pharmacologically altered blood pressure using an alternative approach-manipulation of the renin-angiotensin system (RAS). Male C57BL6/J mice were treated with angiotensin or captopril to elevate and reduce blood pressure, respectively and then exposed to 24-h of sleep fragmentation (SF) or allowed to sleep (control). Pro- and anti-inflammatory cytokine gene expression and as endothelial adhesion gene expression as well as serum glucocorticoids (corticosterone) were measured. RAS manipulation elevated cytokines and endothelial adhesion expression in heart and aorta while SF increased cytokine expression in peripheral tissues, but not brain. However, there were interactive effects of angiotensin-II and SF upon cytokine gene expression in hippocampus and hypothalamus, but not prefrontal cortex. SF, but not RAS manipulation, elevated serum corticosterone concentration. These findings highlight the contrasting effects of RAS manipulation and SF, implying that inflammation from SF is acting on different pathways that are largely independent of RAS manipulation

Design and rationale of FINE-REAL: A prospective study of finerenone in clinical practice

AIMS: Contemporary patterns of care of patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) and the adoption of finerenone are not known. The FINE-REAL study (NCT05348733) is a prospective observational study in patients with CKD and T2D to provide insights into the use of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in clinical practice. METHODS: FINE-REAL is an international, prospective, multicenter, single-arm study enrolling approximately 5500 adults with CKD and T2D in an estimated 200 sites across 22 countries. The study is anticipated to be ongoing until 2027. RESULTS: The primary objective is to describe treatment patterns in patients with CKD and T2D treated with finerenone in routine clinical practice. Secondary objectives include assessment of safety with finerenone. Other endpoints include characterization of healthcare resource utilization and occurrence of newly diagnosed diabetic retinopathy or its progression from baseline in patients with existing disease. A biobank is being organized for future explorative analyses with inclusion of participants from the United States. CONCLUSIONS: FINE-REAL is the first prospective observational study with a nonsteroidal MRA in a population with CKD and T2D and is expected to provide meaningful insights into the treatment of CKD associated with T2D. FINE-REAL will inform decision-making with respect to initiation of finerenone in patients with CKD and T2D

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia

BACKGROUND: Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor beta (TGF-beta) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. METHODS: We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-beta-receptor proteins, including endoglin and activin-receptor-like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. RESULTS: We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activin-receptor-like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor-like kinase 1 in normal and diseased pulmonary arteries. CONCLUSIONS: Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension

The Douglas-Fir Genome Sequence Reveals Specialization of the Photosynthetic Apparatus in Pinaceae.

A reference genome sequence for Pseudotsuga menziesii var. menziesii (Mirb.) Franco (Coastal Douglas-fir) is reported, thus providing a reference sequence for a third genus of the family Pinaceae. The contiguity and quality of the genome assembly far exceeds that of other conifer reference genome sequences (contig N50 = 44,136 bp and scaffold N50 = 340,704 bp). Incremental improvements in sequencing and assembly technologies are in part responsible for the higher quality reference genome, but it may also be due to a slightly lower exact repeat content in Douglas-fir vs. pine and spruce. Comparative genome annotation with angiosperm species reveals gene-family expansion and contraction in Douglas-fir and other conifers which may account for some of the major morphological and physiological differences between the two major plant groups. Notable differences in the size of the NDH-complex gene family and genes underlying the functional basis of shade tolerance/intolerance were observed. This reference genome sequence not only provides an important resource for Douglas-fir breeders and geneticists but also sheds additional light on the evolutionary processes that have led to the divergence of modern angiosperms from the more ancient gymnosperms

Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice

Sleep is a recuperative process, and its dysregulation has cognitive, metabolic, and immunological effects that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammation are not fully understood. To assess the effects of the SNS upon inflammatory responses to SF, C57BL/6j female mice were placed in automated SF chambers with horizontally moving bars across the bottom of each cage at specified intervals to disrupt sleep. Mice were first subjected to either control (no bar movement), acute sleep fragmentation (ASF), or chronic sleep fragmentation (CSF) on a 12:12-h light/dark schedule. ASF involved a bar sweep every 120 s for 24 h, whereas CSF involved a bar sweep every 120 s for 12 h (during 12 L; resting period) over a period of 4 weeks. After exposure to these conditions, mice received an intraperitoneal injection of either phentolamine (5 mg/kg BW; an α-adrenergic receptor blocker), propranolol (5 mg/kg BW; a β-adrenergic receptor blocker), or vehicle (saline). Serum corticosterone concentration, brain and peripheral cytokine (IL1β, TNFα, and TGFβ) mRNA expression, and body mass were assessed. ASF and CSF significantly elevated serum corticosterone concentrations as well as cytokine mRNA expression levels compared with controls, and mice subjected to CSF had decreased body mass relative to controls. Mice subjected to CSF and treated with phentolamine or propranolol had a greater propensity for a decrease in cytokine gene expression compared with ASF, but effects were tissue-specific. Taken together, these results suggest that both α- and β-adrenergic receptors contribute to the SNS mediation of inflammatory responses, and adrenergic antagonists may effectively mitigate tissue-specific SF-mediated inflammation

Limits from the Hubble Space Telescope on a Point Source in SN 1987A

We observed supernova 1987A (SN 1987A) with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope (HST) in 1999 September, and again with the Advanced Camera for Surveys (ACS) on the HST in 2003 November. No point source is observed in the remnant. We obtain a limiting flux of F_opt < 1.6 x 10^{-14} ergs/s/cm^2 in the wavelength range 2900-9650 Angstroms for any continuum emitter at the center of the supernova remnant (SNR). It is likely that the SNR contains opaque dust that absorbs UV and optical emission, resulting in an attenuation of ~35% due to dust absorption in the SNR. Taking into account dust absorption in the remnant, we find a limit of L_opt < 8 x 10^{33} ergs/s. We compare this upper bound with empirical evidence from point sources in other supernova remnants, and with theoretical models for possible compact sources. Bright young pulsars such as Kes 75 or the Crab pulsar are excluded by optical and X-ray limits on SN 1987A. Of the young pulsars known to be associated with SNRs, those with ages < 5000 years are all too bright in X-rays to be compatible with the limits on SN 1987A. Examining theoretical models for accretion onto a compact object, we find that spherical accretion onto a neutron star is firmly ruled out, and that spherical accretion onto a black hole is possible only if there is a larger amount of dust absorption in the remnant than predicted. In the case of thin-disk accretion, our flux limit requires a small disk, no larger than 10^{10} cm, with an accretion rate no more than 0.3 times the Eddington accretion rate. Possible ways to hide a surviving compact object include the removal of all surrounding material at early times by a photon-driven wind, a small accretion disk, or very high levels of dust absorption in the remnant.Comment: 40 pages, 5 figures. AAStex. Accepted, ApJ 04/28/200

Vacuum Energy Density Fluctuations in Minkowski and Casimir States via Smeared Quantum Fields and Point Separation

We present calculations of the variance of fluctuations and of the mean of the energy momentum tensor of a massless scalar field for the Minkowski and Casimir vacua as a function of an intrinsic scale defined by a smeared field or by point separation. We point out that contrary to prior claims, the ratio of variance to mean-squared being of the order unity is not necessarily a good criterion for measuring the invalidity of semiclassical gravity. For the Casimir topology we obtain expressions for the variance to mean-squared ratio as a function of the intrinsic scale (defined by a smeared field) compared to the extrinsic scale (defined by the separation of the plates, or the periodicity of space). Our results make it possible to identify the spatial extent where negative energy density prevails which could be useful for studying quantum field effects in worm holes and baby universe, and for examining the design feasibility of real-life `time-machines'. For the Minkowski vacuum we find that the ratio of the variance to the mean-squared, calculated from the coincidence limit, is identical to the value of the Casimir case at the same limit for spatial point separation while identical to the value of a hot flat space result with a temporal point-separation. We analyze the origin of divergences in the fluctuations of the energy density and discuss choices in formulating a procedure for their removal, thus raising new questions into the uniqueness and even the very meaning of regularization of the energy momentum tensor for quantum fields in curved or even flat spacetimes when spacetime is viewed as having an extended structure.Comment: 41 pages, 2 figure