Resonant X-ray excitation of the nuclear clock isomer 45Sc.

Resonant oscillators with stable frequencies and large quality factors help us to keep track of time with high precision. Examples range from quartz crystal oscillators in wristwatches to atomic oscillators in atomic clocks, which are, at present, our most precise time measurement devices1. The search for more stable and convenient reference oscillators is continuing2-6. Nuclear oscillators are better than atomic oscillators because of their naturally higher quality factors and higher resilience against external perturbations7-9. One of the most promising cases is an ultra-narrow nuclear resonance transition in 45Sc between the ground state and the 12.4-keV isomeric state with a long lifetime of 0.47 s (ref. 10). The scientific potential of 45Sc was realized long ago, but applications require 45Sc resonant excitation, which in turn requires accelerator-driven, high-brightness X-ray sources11 that have become available only recently. Here we report on resonant X-ray excitation of the 45Sc isomeric state by irradiation of Sc-metal foil with 12.4-keV photon pulses from a state-of-the-art X-ray free-electron laser and subsequent detection of nuclear decay products. Simultaneously, the transition energy was determined as [Formula: see text] with an uncertainty that is two orders of magnitude smaller than the previously known values. These advancements enable the application of this isomer in extreme metrology, nuclear clock technology, ultra-high-precision spectroscopy and similar applications.

A Single-Cell Atlas of the Murine Pancreatic Ductal Tree Identifies Novel Cell Populations With Potential Implications in Pancreas Regeneration and Exocrine Pathogenesis.

BACKGROUND & AIMS: Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized; therefore, our understanding of the role of ductal cells in pancreas regeneration and exocrine pathogenesis has been hampered by the limited knowledge and unexplained diversity within the ductal network. METHODS: We used single cell RNA sequencing to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells to the main duct. Moreover, we used organoid cultures, injury models, and pancreatic tumor samples to interrogate the role of novel ductal populations in pancreas regeneration and exocrine pathogenesis. RESULTS: We have identified the coexistence of 15 ductal populations within the healthy pancreas and characterized their organoid formation capacity and endocrine differentiation potential. Cluster isolation and subsequent culturing let us identify ductal cell populations with high organoid formation capacity and endocrine and exocrine differentiation potential in vitro, including a Wnt-responsive population, a ciliated population, and Flrt3+ cells. Moreover, we have characterized the location of these novel ductal populations in healthy pancreas, chronic pancreatitis, and tumor samples. The expression of Wnt-responsive, interferon-responsive, and epithelial-to-mesenchymal transition population markers increases in chronic pancreatitis and tumor samples. CONCLUSIONS: In light of our discovery of previously unidentified ductal populations, we unmask potential roles of specific ductal populations in pancreas regeneration and exocrine pathogenesis. Thus, novel lineage-tracing models are needed to investigate ductal-specific populations in vivo.

Wildlife susceptibility to infectious diseases at global scales.

Disease transmission prediction across wildlife is crucial for risk assessment of emerging infectious diseases. Susceptibility of host species to pathogens is influenced by the geographic, environmental, and phylogenetic context of the specific system under study. We used machine learning to analyze how such variables influence pathogen incidence for multihost pathogen assemblages, including one of direct transmission (coronaviruses and bats) and two vector-borne systems (West Nile Virus [WNV] and birds, and malaria and birds). Here we show that this methodology is able to provide reliable global spatial susceptibility predictions for the studied host-pathogen systems, even when using a small amount of incidence information (i.e., [Formula: see text] of information in a database). We found that avian malaria was mostly affected by environmental factors and by an interaction between phylogeny and geography, and WNV susceptibility was mostly influenced by phylogeny and by the interaction between geographic and environmental distances, whereas coronavirus susceptibility was mostly affected by geography. This approach will help to direct surveillance and field efforts providing cost-effective decisions on where to invest limited resources.

X-ray beam diagnostics at the MID instrument of the European X-ray Free-Electron Laser Facility.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network.

BACKGROUND: Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells. METHODS: EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide. RESULTS: GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88. CONCLUSION: Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment.

Transcranial direct current stimulation over the left posterior temporal lobe modulates semantic control: Evidence from episodic memory distortions.

Evidence accumulates to show that semantic cognition requires, in addition to semantic representations, control processes that regulate the accessibility and use of semantic knowledge in a task- and time-appropriate fashion. Semantic control has been recently proposed to rely on a distributed network that includes the posterior temporal cortex. Along these lines, recent meta-analyses of neuroimaging data and studies with patients suffering from semantic aphasia have suggested that the left posterior middle temporal gyrus (pMTG) is critically involved whenever situational context must constrain semantic retrieval. In the present experiment, we used transcranial direct current stimulation over the left posterior temporal lobe in an attempt to interfere with semantic control while participants performed a DRM task, a procedure for inducing conceptually-based false recognition that is contingent on both activation and control processes. Paralleling findings with patients suffering from brain damage restricted to the temporoparietal cortex, anodal stimulation (relative to sham stimulation) resulted in increased false recognition but intact true recognition. These findings fit well with the idea that the left pMTG is a key component of a semantic control network, the alteration of which results in memory performance that is affected by the intrusion of contextually-inappropriate semantic information.

Modeling oceanic sedimentary methane hydrate growth through molecular dynamics simulation.

The crystallization process of methane hydrates in a confined geometry resembling seabed porous silica sedimentary conditions has been studied using molecular dynamics simulations. With this objective in mind, a fully atomistic quartz silica slit pore has been designed, and the temperature stability of a methane hydrate crystalline seed in the presence of water and guest molecule methane has been analyzed. NaCl ion pairs have been added in different concentrations, simulating salinity conditions up to values higher than average oceanic conditions. The structure obtained when the hydrate crystallizes inside the pore is discussed, paying special attention to the presence of ionic doping inside the hydrate and the subsequent induced structural distortion. The shift in the hydrate stability conditions due to the increasing water salinity is discussed and compared with the case of unconfined hydrate, concluding that the influence of the confinement geometry and pore hydrophilicity produces a larger deviation in the confined hydrate phase equilibria.

Seasonality analysis on cryopreserved doses from the autochthonous cattle breeds Asturiana de la Montaña and Asturiana de los Valles.

Germplasm banking is a fundamental tool for the preservation of autochthonous breeds. Semen cryopreservation is effective for this task, but protocols are adapted to commercial species, and post-thawing sperm quality could be sensitive to environmental cues. We compared the post-thawing sperm quality in doses from the CBA-SERIDA bank in northern Spain for the Asturiana de la Montaña (AM) and Asturiana de los Valles (AV) autochthonous cattle breeds. Doses from 23 AM and 16 AV bulls (ejaculates from at least three different seasons) were assessed for motility (computer-assisted sperm analysis), physiology and chromatin status (flow cytometry) after thawing and after 5 h at 38°C. Data were analysed using linear mixed-effects and cosinor models for seasonal and breed effects and by correlations with the association of sperm quality with temperature-humidity index (THI), considering the interval of spermatogenesis plus maturation. The breed affected sperm quality, with higher motility for AV and higher apoptotic ratio, mitochondrial activity, reactive oxygen species, DNA fragmentation and chromatin immaturity for AM. However, seasonality effects were minimal, and THI was not associated with sperm quality. In summary, the season seems to be a minor factor in the post-thawing quality of the AM and AV autochthonous breeds, well-adapted to their local environment.

Syntactic and emotional interplay in second language: emotional resonance but not proficiency modulates affective influences on L2 syntactic processing.

Previous research has demonstrated the influence of emotions during linguistic processing, indicating the interactivity of both processes in the brain. However, little is known regarding such interplay in a second language (L2). This study addressed this question by examining the reading effects of syntactic violations while processing L2 emotional and neutral statements. Forty-six Spanish-English bilinguals with various levels of L2 proficiency and emotional resonance (i.e. capability for emotional experience in L2) were presented with a self-paced sentence reading task. Sentences contained positive (16), neutral (16) and negative (16) verbs, half of them presented in agreement and half in disagreement with the preceding pronoun. Analysis of verb reading times using linear mixed effects modelling revealed a significant interaction between syntactic violation, verb valence and emotional resonance, suggesting that stronger emotional L2 experience results in a higher saliency of negative verbs, reducing the impact of syntactic violations.

Uncommon gastric hernia in parastomal defect.

An 84-year-old woman with a Barthel Index of 40 and a history of rectal adenocarcinoma treated with total mesorectal excision and colostomy presented with a 24-hour history of abdominal pain, vomiting, and a defunctioning ileostomy. Examination revealed hemodynamic instability, a distended abdomen, and diffuse tenderness around the parastomal hernia. CT scan revealed significant gastric dilation extending through the parastomal hernia with obstructive changes at the gastroduodenal junction. Parastomal hernias are relatively common, with an incidence of 0-48.1%.

Spin cascade and doming in ferric hemes: Femtosecond X-ray absorption and X-ray emission studies.

The structure-function relationship is at the heart of biology, and major protein deformations are correlated to specific functions. For ferrous heme proteins, doming is associated with the respiratory function in hemoglobin and myoglobins. Cytochrome c (Cyt c) has evolved to become an important electron-transfer protein in humans. In its ferrous form, it undergoes ligand release and doming upon photoexcitation, but its ferric form does not release the distal ligand, while the return to the ground state has been attributed to thermal relaxation. Here, by combining femtosecond Fe Kα and Kß X-ray emission spectroscopy (XES) with Fe K-edge X-ray absorption near-edge structure (XANES), we demonstrate that the photocycle of ferric Cyt c is entirely due to a cascade among excited spin states of the iron ion, causing the ferric heme to undergo doming, which we identify. We also argue that this pattern is common to a wide diversity of ferric heme proteins, raising the question of the biological relevance of doming in such proteins.

Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1ß (IL-1ß); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 ß, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.

Synergism between obesity and HFpEF on neutrophils phenotype and its regulation by adipose tissue-molecules and SGLT2i dapagliflozin.

The adiposity invokes innate immune activity, coronary microvascular dysfunction and consequently heart failure preserved ejection fraction (HFpEF). Our aim was to study the neutrophils profile on obesity and cardiovascular disease and its regulation by adipose tissue-secretome and dapagliflozin. We have isolated neutrophils from patients undergoing open heart surgery (19 women and 51 men). Its migration activity was performed with culture-transwell, transcriptional studies of proteolytic enzymes, adhesion molecules or receptors were analysed by real-time PCR and proteomics (from 20 patients) analysis by TripleTOF mass spectrometer. Differentiated HL-60 (dHL-60) was used as a preclinical model on microfluidic for endothelial cells attaching assays and genes regulation with epicardial and subcutaneous fat secretomes from patients (3 women and 9 men) or dapagliflozin 1-10 µM treatments. The transcriptional and proteomics studies have determined higher levels of adhesion molecules in neutrophils from patients with obesity. The adhesion molecule CD11b levels were higher in those patients with the combined obesity and HFpEF factors (1.70 ± 0.06 a.u. without obesity, 1.72 ± 0.04 a.u. obesity or HFpEF without obesity and 1.79 ± 0.08 a.u. obesity and HFpEF; p < .01). While fat-secretome induces its upregulation, dapagliflozin can modulated it. Because CD11b upregulation is associated with higher neutrophils migration and adhesion into endothelial cells, dapagliflozin might modulate this mechanism on patients with obesity and HFpEF.

Design and performance of a dedicated coherent X-ray scanning diffraction instrument at beamline NanoMAX of MAX IV.

The diffraction endstation of the NanoMAX beamline is designed to provide high-flux coherent X-ray nano-beams for experiments requiring many degrees of freedom for sample and detector. The endstation is equipped with high-efficiency Kirkpatrick-Baez mirror focusing optics and a two-circle goniometer supporting a positioning and scanning device, designed to carry a compact sample environment. A robot is used as a detector arm. The endstation, in continued development, has been in user operation since summer 2017.

Multi-modal characterization of kesterite thin-film solar cells: experimental results and numerical interpretation.

We report a multi-modal study of the electrical, chemical and structural properties of a kesterite thin-film solar cell by combining the spatially-resolved X-ray beam induced current and fluorescence imaging techniques for the evaluation of a fully functional device on a cross-section. The data allowed the correlation of the chemical composition, defects at interfaces and inhomogeneous deposition of the layers with the local charge-collection efficiency of the device. We support our observations with Monte Carlo simulations of high-energy X-ray interactions with the semiconductor device, and finite-volume modeling of the charge-collection efficiency.

Absence of post-learning motor activity effects on memory for motor-related words.

Drawing a hypothesis from embodied theories of memory, van Dam, Rueschemeyer, Bekkering and Lindemann [(2013). Embodied grounding of memory: Toward the effects of motor execution on memory consolidation. The Quarterly Journal of Experimental Psychology, 66(12), 2310-2328] showed that recognition performance for action words could be modulated by actions performed during the retention interval, suggesting that motor actions during the retention interval affect memory consolidation. The results of 4 experiments from two different laboratories, designed to replicate and extend the van Dam et al. motor consolidation effect, are presented here. Two of the experiments (n = 30 and n = 44) exactly and independently replicated the experimental design and conditions of the original experiment. Yes/No recognition scores plus additional analysis of response times showed no motor consolidation effects. A third experiment (n = 44) manipulating type of processing during encoding also failed to find significant motor consolidation effects. Finally, a fourth experiment (n = 120) following a more standard reconsolidation paradigm, involving 24-hour intervals between learning and motor behaviour, and a 24-hour delayed test, also found null effects. The absence of effects of motor execution on memory consolidation is discussed in terms of the implications of these findings for the embodiment approach to cognition.

The use of sutureless and rapid-deployment aortic valve prosthesis in patients with bicuspid aortic valve: A focused review.

OBJECTIVE: The objective of this scoping review is to describe the postoperative outcomes and complications of patients with bicuspid aortic valve (BAV) treated with sutureless or rapid-deployment prosthesis. BACKGROUND: The use of sutureless and rapid-deployment prostheses is generally avoided in patients with BAV due to anatomical concerns and the elevated risk of para-prosthetic leaks. Multiple studies have reported the use of these prostheses into patients with BAV with varying degrees of success. The focus of this review is to consolidate the current available evidence on this topic. METHODS: A scoping review was conducted using a comprehensive search strategy in multiple databases (Medline, Embase, Cochrane Central Register of Controlled Clinical Trials) for relevant articles. All abstracts and full texts were screened by two independent reviewers according to predefined inclusion and exclusion criteria. Thirteen articles, including case reports and case series were ultimately included for analysis. RESULTS: Of 1052 total citations, 44 underwent full text review and 13 (4 case reports, 6 retrospective analyses, and 3 prospective analyses) were included in the scoping review. Across all 13 studies, a total of 314 patients with BAV were used for data analysis. In sutureless and rapid-deployment prostheses, the mean postoperative aortic valvular gradients were less than 15 mmHg in all studies with mean postoperative aortic valvular areas all greater than 1.3 cm.2 There were 186 total complications for an overall complication rate of 59%. Individual complications included new onset atrial fibrillation (n = 65), required pacemaker insertion (n = 24), intraprosthetic aortic regurgitation (n = 20), new onset atrioventricular block (n = 18), and new onset paravalvular leakage (n = 10). CONCLUSIONS: The use of sutureless and rapid deployment prostheses in patients with BAV showed comparable intraoperative and implantation success rates to patients without BAV. Postoperative complications from using these prostheses in patients with BAV included new onset atrial fibrillation, intraprosthetic aortic regurgitation, new onset atrioventricular block, and required pacemaker insertion. Various techniques have been described to minimize these complications in patients with BAV receiving sutureless or rapid deployment prostheses.

Effectiveness of intra-operative topical amiodarone for prevention of postcardiac surgery new-onset atrial fibrillation: A review of current evidence.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common complications following cardiac surgery and is associated with increased morbidity. Intraoperative topical amiodarone application on epicardial tissue has been shown to reduce systemic concentrations while maintaining therapeutic myocardial concentrations, thereby, lowering the risk of extracardiac adverse effects associated with oral and intravenous amiodarone therapy. However, the efficacy and safety of topical amiodarone in preventing POAF is unclear. OBJECTIVES: This study summarizes the clinical studies to-date that have investigated the efficacy and safety of topical amiodarone administration in preventing POAF following cardiac surgery. METHODS: A database search was conducted using Medline, Embase, and Cochrane Library to identify relevant studies. Abstracts were screened and data were extracted from relevant full-text articles that met the inclusion and exclusion criteria. RESULTS: The search returned four studies with variable findings on the effect of topical amiodarone therapy on the incidence of POAF, cardiac effects, extracardiac effects, and hospital length of stay. CONCLUSION: Prophylactic topical application of amiodarone may be effective and safe for preventing post-operative new-onset atrial fibrillation. Further investigation is required to evaluate the efficacy and safety of topical amiodadrone therapy before it can be widely integrated into current practice.

Biomechanical characteristics of different methods of neo-chordal fixation to the papillary muscles.

BACKGROUND AND AIM OF THE STUDY: Several techniques have been described for neo-chordal fixation to the papillary muscles without any reported clinical differences. The objective of this study is to compare in vitro the biomechanical properties of four of these common techniques. METHODS: We studied the biomechanical properties of expanded polytetrafluoroethylene neo-chordal fixation using four techniques: nonknotted simple stitch, nonknotted figure-of-eight stitch, knotted pledgeted mattress stitch, and knotted pledgeted stitch using commercially available prefabricated loops. Neo-chordae were submitted to a total of 20 traction-relaxation cycles with incremental loads of 1, 2, and 4 N. We calculated the elongation, the force-strain curve, elasticity, and the maximum tolerated load before neo-chordal failure. RESULTS: The elongation of the neo-chordae was lowest in the simple stitch followed by the figure-of-eight, the pledgeted mattress, and he commercially prefabricated loops (p < .001). Conversely, the elastic modulus was highest in the simple stitch followed by the figure-of-eight, the pledgeted mattress, and the prefabricated loops (p < .001). The maximum tolerated load was similar with the simple stitch (28.87 N) and with the figure-of-eight stitch (31.39 N) but was significantly lower with the pledgeted mattress stitch (20.51 N) and with the prefabricated loops (7.78 N). CONCLUSION: In vitro, neo-chordal fixation by nonknotted simple or nonknotted figure-of-eight stitches resulted in less compliance as opposed to the use of knotted pledgeted stitches. Fixation technique seemed to influence neo-chordal biomechanical properties, however, it did not seem to affect the strength of the suture when subjected to loads within physiological ranges.

NanoMAX: the hard X-ray nanoprobe beamline at the MAX IV Laboratory.

NanoMAX is the first hard X-ray nanoprobe beamline at the MAX IV laboratory. It utilizes the unique properties of the world's first operational multi-bend achromat storage ring to provide an intense and coherent focused beam for experiments with several methods. In this paper we present the beamline optics design in detail, show the performance figures, and give an overview of the surrounding infrastructure and the operational diffraction endstation.