38 research outputs found
Data Mesh: Motivational Factors, Challenges, and Best Practices
With the increasing importance of data and artificial intelligence,
organizations strive to become more data-driven. However, current data
architectures are not necessarily designed to keep up with the scale and scope
of data and analytics use cases. In fact, existing architectures often fail to
deliver the promised value associated with them. Data mesh is a socio-technical
concept that includes architectural aspects to promote data democratization and
enables organizations to become truly data-driven. As the concept of data mesh
is still novel, it lacks empirical insights from the field. Specifically, an
understanding of the motivational factors for introducing data mesh, the
associated challenges, best practices, its business impact, and potential
archetypes, is missing. To address this gap, we conduct 15 semi-structured
interviews with industry experts. Our results show, among other insights, that
industry experts have difficulties with the transition toward federated
governance associated with the data mesh concept, the shift of responsibility
for the development, provision, and maintenance of data products, and the
concept of a data product model. In our work, we derive multiple best practices
and suggest organizations embrace elements of data fabric, observe the data
product usage, create quick wins in the early phases, and favor small dedicated
teams that prioritize data products. While we acknowledge that organizations
need to apply best practices according to their individual needs, we also
deduct two archetypes that provide suggestions in more detail. Our findings
synthesize insights from industry experts and provide researchers and
professionals with guidelines for the successful adoption of data mesh
Oxidative Stress and Inflammatory Modulation of Ca2+ Handling in Metabolic HFpEF-Related Left Atrial Cardiomyopathy
Metabolic syndrome-mediated heart failure with preserved ejection fraction (HFpEF) is commonly accompanied by left atrial (LA) cardiomyopathy, significantly affecting morbidity and mortality. We evaluate the role of reactive oxygen species (ROS) and intrinsic inflammation (TNF-α, IL-10) related to dysfunctional Ca2+ homeostasis of LA cardiomyocytes in a rat model of metabolic HFpEF. ZFS-1 obese rats showed features of HFpEF and atrial cardiomyopathy in vivo: increased left ventricular (LV) mass, E/e' and LA size and preserved LV ejection fraction. In vitro, LA cardiomyocytes exhibited more mitochondrial-fission (MitoTracker) and ROS-production (H2DCF). In wildtype (WT), pro-inflammatory TNF-α impaired cellular Ca2+ homeostasis, while anti-inflammatory IL-10 had no notable effect (confocal microscopy; Fluo-4). In HFpEF, TNF-α had no effect on Ca2+ homeostasis associated with decreased TNF-α receptor expression (western blot). In addition, IL-10 substantially improved Ca2+ release and reuptake, while IL-10 receptor-1 expression was unaltered. Oxidative stress in metabolic syndrome mediated LA cardiomyopathy was increased and anti-inflammatory treatment positively affected dysfunctional Ca2+ homeostasis. Our data indicates, that patients with HFpEF-related LA dysfunction might profit from IL-10 targeted therapy, which should be further explored in preclinical trials
Right‐ventricular dysfunction in HFpEF is linked to altered cardiomyocyte Ca2+ homeostasis and myofilament sensitivity
Aim
Heart failure with preserved ejection fraction (HFpEF) is frequently (30%) associated with right ventricular (RV) dysfunction, which increases morbidity and mortality in these patients. Yet cellular mechanisms of RV remodelling and RV dysfunction in HFpEF are not well understood. Here, we evaluated RV cardiomyocyte function in a rat model of metabolically induced HFpEF.
Methods: and results Heart failure with preserved ejection fraction-prone animals (ZSF-1 obese) and control rats (Wistar Kyoto) were fed a high-caloric diet for 13 weeks. Haemodynamic characterization by echocardiography and invasive catheterization was performed at 22 and 23 weeks of age, respectively. After sacrifice, organ morphometry, RV histology, isolated RV cardiomyocyte function, and calcium (Ca2+) transients were assessed. ZSF-1 obese rats showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV diastolic dysfunction (including increased LV end-diastolic pressures and E/e ' ratio), and preserved LV ejection fraction. ZSF-1 obese animals developed RV dilatation (50% increased end-diastolic area) and mildly impaired RV ejection fraction (42%) with evidence of RV hypertrophy. In isolated RV cardiomyocytes from ZSF-1 obese rats, cell shortening amplitude was preserved, but cytosolic Ca2+ transient amplitude was reduced. In addition, augmentation of cytosolic Ca2+ release with increased stimulation frequency was lost in ZSF-1 obese rats. Myofilament sensitivity was increased, while contractile kinetics were largely unaffected in intact isolated RV cardiomyocytes from ZSF-1 obese rats. Western blot analysis revealed significantly increased phosphorylation of cardiac myosin-binding protein C (Ser282 cMyBP-C) but no change in phosphorylation of troponin I (Ser23, 24 TnI) in RV myocardium from ZSF-1 obese rats.
Conclusions: Right ventricular dysfunction in obese ZSF-1 rats with HFpEF is associated with intrinsic RV cardiomyocyte remodelling including reduced cytosolic Ca2+ amplitudes, loss of frequency-dependent augmentation of Ca2+ release, and increased myofilament Ca2+ sensitivity
Effects of different exercise modalities on cardiac dysfunction in heart failure with preserved ejection fraction
Aims: Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent disease. Physical exercise has been shown to alter disease progression in HFpEF. We examined cardiomyocyte Ca2+ homeostasis and left ventricular function in a metabolic HFpEF model in sedentary and trained rats following 8 weeks of moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT).
Methods and results: Left ventricular in vivo function (echocardiography) and cardiomyocyte Ca2+ transients (CaTs) (Fluo-4, confocal) were compared in ZSF-1 obese (metabolic syndrome, HFpEF) and ZSF-1 lean (control) 21- and 28-week-old rats. At 21 weeks, cardiomyocytes from HFpEF rats showed prolonged Ca-2(+) reuptake in cytosolic and nuclear CaTs and impaired Ca2+ release kinetics in nuclear CaTs. At 28 weeks, HFpEF cardiomyocytes had depressed CaT amplitudes, decreased sarcoplasmic reticulum (SR) Ca2+ content, increased SR Ca2+ leak, and elevated diastolic [Ca2+] following increased pacing rate (5 Hz). In trained HFpEF rats (HIIT or MICT), cardiomyocyte SR Ca2+ leak was significantly reduced. While HIIT had no effects on the CaTs (1-5 Hz), MICT accelerated early Ca-2(+) release, reduced the amplitude, and prolonged the CaT without increasing diastolic [Ca2+] or cytosolic Ca2+ load at basal or increased pacing rate (1-5 Hz). MICT lowered pro-arrhythmogenic Ca2+ sparks and attenuated Ca2+-wave propagation in cardiomyocytes. MICT was associated with increased stroke volume in HFpEF.
Conclusions: In this metabolic rat model of HFpEF at an advanced stage, Ca2+ release was impaired under baseline conditions. HIIT and MICT differentially affected Ca2+ homeostasis with positive effects of MICT on stroke volume, end-diastolic volume, and cellular arrhythmogenicity
Dual SGLT-1 and SGLT-2 inhibition improves left atrial dysfunction in HFpEF
Background: Sodium-glucose linked transporter type 2 (SGLT-2) inhibition has been shown to reduce cardiovascular mortality in heart failure independently of glycemic control and prevents the onset of atrial arrhythmias, a common co-morbidity in heart failure with preserved ejection fraction (HFpEF). The mechanism behind these effects is not fully understood, and it remains unclear if they could be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1&2 inhibitor sotagliflozin on left atrial (LA) remodeling and cellular arrhythmogenesis (i.e. atrial cardiomyopathy) in a metabolic syndrome-related rat model of HFpEF.
Methods: 17 week-old ZSF-1 obese rats, a metabolic syndrome-related model of HFpEF, and wild type rats (Wistar Kyoto), were fed 30 mg/kg/d sotagliflozin for 6 weeks. At 23 weeks, LA were imaged in-vivo by echocardiography. In-vitro, Ca2+ transients (CaT; electrically stimulated, caffeine-induced) and spontaneous Ca2+ release were recorded by ratiometric microscopy using Ca2+-sensitive fluorescent dyes (Fura-2) during various experimental protocols. Mitochondrial structure (dye: Mitotracker), Ca2+ buffer capacity (dye: Rhod-2), mitochondrial depolarization (dye: TMRE) and production of reactive oxygen species (dye: H2DCF) were visualized by confocal microscopy. Statistical analysis was performed with 2-way analysis of variance followed by post-hoc Bonferroni and student's t-test, as applicable.
Results: Sotagliflozin ameliorated LA enlargement in HFpEF in-vivo. In-vitro, LA cardiomyocytes in HFpEF showed an increased incidence and amplitude of arrhythmic spontaneous Ca2+ release events (SCaEs). Sotagliflozin significantly reduced the magnitude of SCaEs, while their frequency was unaffected. Sotagliflozin lowered diastolic [Ca2+] of CaT at baseline and in response to glucose influx, possibly related to a similar to 50% increase of sodium sodium-calcium exchanger (NCX) forward-mode activity. Sotagliflozin prevented mitochondrial swelling and enhanced mitochondrial Ca2+ buffer capacity in HFpEF. Sotagliflozin improved mitochondrial fission and reactive oxygen species (ROS) production during glucose starvation and averted Ca2+ accumulation upon glycolytic inhibition.
Conclusion: The SGLT-1&2 inhibitor sotagliflozin ameliorated LA remodeling in metabolic HFpEF. It also improved distinct features of Ca2+-mediated cellular arrhythmogenesis in-vitro (i.e. magnitude of SCaEs, mitochondrial Ca2+ buffer capacity, diastolic Ca2+ accumulation, NCX activity). The safety and efficacy of combined SGLT-1&2 inhibition for the treatment and/or prevention of atrial cardiomyopathy associated arrhythmias should be further evaluated in clinical trials
Electrical detection of magnetic skyrmions by non-collinear magnetoresistance
Magnetic skyrmions are localised non-collinear spin textures with high
potential for future spintronic applications. Skyrmion phases have been
discovered in a number of materials and a focus of current research is the
preparation, detection, and manipulation of individual skyrmions for an
implementation in devices. Local experimental characterization of skyrmions has
been performed by, e.g., Lorentz microscopy or atomic-scale tunnel
magnetoresistance measurements using spin-polarised scanning tunneling
microscopy. Here, we report on a drastic change of the differential tunnel
conductance for magnetic skyrmions arising from their non-collinearity: mixing
between the spin channels locally alters the electronic structure, making a
skyrmion electronically distinct from its ferromagnetic environment. We propose
this non-collinear magnetoresistance (NCMR) as a reliable all-electrical
detection scheme for skyrmions with an easy implementation into device
architectures
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High density lipoprotein mediates anti-inflammatory transcriptional reprogramming of macrophages via the transcriptional repressor ATF3
High Density Lipoprotein (HDL) mediates reverse cholesterol transport and it is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional repressor ATF3, as an HDL-inducible target gene in macrophages that down-regulates the expression of Toll-like receptor (TLR)-induced pro-inflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of novel HDL-based therapies
Reconnecting Stochastic Methods With Hydrogeological Applications: A Utilitarian Uncertainty Analysis and Risk Assessment Approach for the Design of Optimal Monitoring Networks
Collaboration between academics and practitioners promotes knowledge transfer between research and industry, with both sides benefiting greatly. However, academic approaches are often not feasible given real-world limits on time, cost and data availability, especially for risk and uncertainty analyses. Although the need for uncertainty quantification and risk assessment are clear, there are few published studies examining how scientific methods can be used in practice. In this work, we introduce possible strategies for transferring and communicating academic approaches to real-world applications, countering the current disconnect between increasingly sophisticated academic methods and methods that work and are accepted in practice. We analyze a collaboration between academics and water suppliers in Germany who wanted to design optimal groundwater monitoring networks for drinking-water well catchments. Our key conclusions are: to prefer multiobjective over single-objective optimization; to replace Monte-Carlo analyses by scenario methods; and to replace data-hungry quantitative risk assessment by easy-to-communicate qualitative methods. For improved communication, it is critical to set up common glossaries of terms to avoid misunderstandings, use striking visualization to communicate key concepts, and jointly and continually revisit the project objectives. Ultimately, these approaches and recommendations are simple and utilitarian enough to be transferred directly to other practical water resource related problems.German Technical and Scientific Association for Gas and Water (DVGW) [Q 1-01-10-F]; German Research Foundation (DFG) through the International Research Training Group NUPUS [IRTG 1398]; Cluster of Excellence in Simulation Technology at the University of Stuttgart [EXC 310/2]6 month embargo; published online: 08 March 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Improvement of Retinal Microcirculation after Pulmonary Vein Isolation in Patients with Atrial Fibrillation—An Optical Coherence Tomography Angiography Study
Purpose: To evaluate retinal and optic nerve head (ONH) perfusion in patients with atrial fibrillation (AF) before and after catheter ablation of AF with pulmonary vein isolation (PVI). Methods: 34 eyes of 34 patients with AF and 35 eyes of 35 healthy subjects were included in this study. Flow density data were obtained using spectral-domain OCT-A (RTVue XR Avanti with AngioVue, Optovue, Inc, Fremont, California, USA). The data of the superficial and deep vascular layers of the macula and the ONH (radial peripapillary capillary network, RPC) before and after PVI were extracted and analysed. Results: The flow density in the superficial OCT-angiogram (whole en face) and the ONH (RPC) in patients with AF was significantly lower compared to healthy controls (OCT-A superficial: study group: 48.77 (45.19; 52.12)%; control group: 53.01 (50.00; 54.25)%; p < 0.001; ONH: study group: 51.82 (48.41; 54.03)%; control group: 56.00 (54.35; 57.70)%; p < 0.001;). The flow density in the ONH (RPC) improved significantly in the study group following PVI (before: 51.82 (48.41; 54.03)%; after: 52.49 (50.34; 55.62)%; p = 0.007). Conclusions: Patients with AF showed altered ocular perfusion as measured using OCTA when compared with healthy controls. Rhythm control using PVI significantly improved ocular perfusion as measured using OCT-A. Non-contact imaging using OCTA provides novel information about the central global microperfusion of patients with AF
Rate of venous thromboembolism in a prospective all-comers cohort with COVID-19
Abstract COVID-19 is associated with a variety of clinical complications including coagulopathy, which frequently results in venous thromboembolism (VTE). Retrospective analyses reported a markedly increased rate of VTEs in COVID-19. However, most recent studies on coagulopathy in COVID-19 were only focused on critically ill patients, and without suitable control groups. We aimed to evaluate the rate of VTEs in an all-comers cohort with suspected COVID-19 during a 30-days follow-up period. We also studied the level of D-dimers and their association with the course of disease. In our prospective single-center study (DRKS00021206, 03/30/2020), we analyzed 190 patients with suspected COVID-19 admitted to the emergency department between March and April 2020. Forty-nine patients were SARS-CoV-2 positive (25.8%). The 141 SARS-CoV-2-negative patients served as control group. After completion of a 30-days follow-up, VTE was diagnosed in 3 patients of the SARS-CoV-2-positive group (6.1%, amongst these 2 ICU cases) versus 5 patients in the SARS-CoV-2-negative group (3.5%), however the difference was not statistically significant (p = 0.427). 30-days mortality was similar in both groups (6.1% vs. 5%, p = 0.720). Disease severity correlated with the maximum level of D-dimers during follow-up in COVID-19. The rate of VTE was numerically higher in SARS-CoV-2 positive all-comers presenting with suspected COVID-19 as compared to well-matched controls suffering from similar symptoms. VTEs in the COVID-19 group predominantly occurred in ICU courses. The maximum level of D-dimers during follow-up was associated with disease severity in COVID-19, whereas the level of D-dimers at admission was not