A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells

A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells. Lactate production and ion fluxes were measured in isolated rat papillary collecting duct cells (PCD) to gain further insight into the transport properties of the papillary collecting duct. Lactate production was found to be inhibited by bumetanide in a dose-dependent manner, a maximum inhibition of 22% was obtained at 10−4 M bumetanide and an apparent Ki of 10−8 M was determined. Bumetanide inhibition of lactate production was dependent on the presence of sodium and chloride. Chloride removal inhibited lactate production also by 20%. Bumetanide (10−4 M) inhibited by 35% sodium uptake into PCD cells exposed to 10mM ouabain and chloride uptake into ion depleted PCD cells by 40%. In addition, this bumetanide-sensitive chloride uptake was dependent on the presence of sodium and potassium in the incubation medium. Furthermore, 86Rb uptake into these cells was significantly reduced in the presence of 10−4 M bumetanide. These data provide evidence for the operation of a Na-K-Cl cotransport system in rat papillary collecting duct cells. This transport system might be involved in active chloride transport in the papillary collecting duct and/or volume regulation of the PCD cells

Estimation of Load-Time Curves Using Recurrent Neural Networks Based On Can Bus Signals

Precise knowledge of the load history of safety-relevant structures is a central aspect within the fatigue strength design of modern vehicles. Since the experimental measurement of load variables is complex and therefore associated with high costs, vehicles require estimation of these variables in order to design even more customer-orientedly in the future and thus consistently pursue sustainable lightweight construction. Hence the data measured by sensors in today's standard production vehicles is based on vehicle bus system signals which can be permanently retrieved. Due to the increasing availability of large quantities of recorded vehicle data, machine learning methods are moving into the focus of application. In this work, the implementation of Recurrent Neural Networks for the estimation of loadtime curves is investigated. In order to close existing gaps in the state of the art, successful concepts of machine learning for sequential data, such as speech processing, are to be transferred to this application case. Long Short-Term Memory cells [1] play a central role for this type of problem. In addition to the adaptation of the network architecture, the integration of engineering knowledge is pursued within the method development process in order to increase the quality of the model. Relevant input variables are specifically selected by feature engineering and new meaningful variables are generated by filtering. Statistical analysis is used to investigate the correlation of these input signals with the estimated quantities. The development of a robust load estimation takes place in the course of model development on the basis of the torque of the left-hand rear drive shaft. Results reveal that the Recurrent Neural Networks approach is justified in estimating the highly nonlinear load curve of a complexly loaded part ­ as a component of the dynamic system ­ by means of available sensor signals [2]. Subsequently, the model is validated using recorded measurement data for different chassis settings of the same vehicle. Finally, the transferability of the designed network configuration to other chassis components of the same vehicle is investigated and evaluated

Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment

Phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) are two key components of the PI3K/Akt/mTOR signaling pathway. This signal transduction cascade regulates a wide range of physiological cell processes, that include differentiation, proliferation, apoptosis, autophagy, metabolism, motility, and exocytosis. However, constitutively active PI3K/Akt/mTOR signaling characterizes many types of tumors where it negatively influences response to therapeutic treatments. Hence, targeting PI3K/Akt/mTOR signaling with small molecule inhibitors may improve cancer patient outcome. The PI3K/Akt/mTOR signaling cascade is overactive in acute leukemias, where it correlates with enhanced drug-resistance and poor prognosis. The catalytic sites of PI3K and mTOR share a high degree of sequence homology. This feature has allowed the synthesis of ATP-competitive compounds targeting the catalytic site of both kinases. In preclinical models, dual PI3K/mTOR inhibitors displayed a much stronger cytotoxicity against acute leukemia cells than either PI3K inhibitors or allosteric mTOR inhibitors, such as rapamycin. At variance with rapamycin, dual PI3K/mTOR inhibitors targeted both mTOR complex 1 and mTOR complex 2, and inhibited the rapamycin-resistant phosphorylation of eukaryotic initiation factor 4E-binding protein 1, resulting in a marked inhibition of oncogenic protein translation. Therefore, they strongly reduced cell proliferation and induced an important apoptotic response. Here, we reviewed the evidence documenting that dual PI3K/mTOR inhibitors may represent a promising option for future targeted therapies of acute leukemia patients

Risk factors for catheter-related infections in patients receiving permanent dialysis catheter

Abstract Background Due to rising vascular comorbidities of patients undergoing dialysis, the prevalence of permanent hemodialysis catheters as hemodialysis access is increasing. However, infection is a major complication of these catheters. Therefore, identification of potential predicting risk factors leading to early infection related complications is valuable, in particular the significance the CRP (C-reactive protein)-value is of interest. Methods In this retrospective study 151 permanent hemodialysis catheters implanted in 130 patients were examined. The following data were collected at the time of catheter implantation: CRP-value, history of catheter-related infection, microbiological status, immunosuppression and diabetes mellitus. The primary outcomes were recorded over the 3 months following the implantation: catheter-related infection, days of hospital stay and death. Catheter removal or revision, rehospitalization and use of antibiotics were identified as secondary outcomes. Results We identified a total of 27 (17.9%) infections (systemic infection: 2.26 episodes/ 1000 catheter days, local infection: 0.6 episodes/ 1000 catheter days). The development of an infection was independent of the CRP-value (p = 0.66) as well as the presence of diabetes mellitus (p = 0.64) or immunosuppression (p = 0.71). Univariate analysis revealed that infection was more frequent in patients with MRSA-carriage (p < 0.001), in case of previous catheter-related infection (p < 0.05) and of bacteremia or bacteriuria in the period of 3 months before catheter implantation (p < 0.001). Catheter removal or revision (p = 0.002), rehospitalization (p = 0.001) and use of antibiotics (p = 0.02) were also more often observed in patients with MRSA-carriage. Conclusions The CRP-value at the time of implantation of a permanent hemodialysis catheter is not associated with the development of early catheter related infections, but an individual history of catheter-related infection, MRSA-carriage and bacteremia or bacteriuria in the period of 3 months prior to catheter implantation are significant risk factors

Osmoregulation of aldose reductase and sorbitol dehydrogenase in cultivated interstitial cells of rat renal inner medulla

Background. Little is known about sorbitol metabolism in renal papillary interstitial cells. For characterization we studied regulation of sorbitol synthesis by aldose reductase (AR) and degradation by sorbitol dehydrogenase (SDH) in papillary interstitial cells. Methods. Interstitial cells were isolated from rat renal inner medulla to a pure cell fraction. mRNA was isolated from cultivated cells and sorbitol, AR and SDH activity were determined enzymatically in homogenates. Results. Sorbitol concentration in these cells at 300 mosmol/l was 4.4 +/- 0.3 vs 78 +/- 3.6 mumol/g protein at 600 mosmol/l. At steady-state conditions at 300 mosmol/l, AR activity was nearly the same as SDH activity (15.1 +/- 1.6 vs 16.6 +/- 2.0 U/g protein). At 600 mosmol/l, AR activity increased to 82.5 +/- 11.4 U/g protein and SDH activity to 31.5 +/- 6.0 U/g protein. Studying the time course of enzyme activity after changing osmolarity from 300 to 600 mosmol/l, we found half maximal stimulation after 2-3 (AR) or 3 (SDH) days. The amount of AR-mRNA preceded the rise of enzyme activity, whereas SDH-mRNA was not significantly influenced. Lowering osmolarity from 600 to 300 mosmol/l, enzyme activity decreased to less than half within 2 (AR) or I (SDH) day(s). Conclusions. The results suggest that sorbitol metabolism contributes to handling of osmotic stress in rat renal papillary interstitial cells

Thrombophilic risk factors in hemodialysis: Association with early vascular access occlusion and patient survival in long-term follow-up.

ObjectiveThrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up.MethodsIn this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed.ResultsAmong the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (PConclusionsTRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion

The role of exercise training on cardiovascular risk factors and heart disease in patients with chronic kidney disease G3-G5 and G5D: A Clinical Consensus Statement of the European Association of Preventive Cardiology (EAPC) of the ESC and the European Association of Rehabilitation in Chronic Kidney Disease (EURORECKD)

From Crossref journal articles via Jisc Publications RouterHistory: epub 2024-04-09, issued 2024-04-09Article version: AMPublication status: PublishedPelagia Koufaki - ORCID: 0000-0002-1406-3729 https://orcid.org/0000-0002-1406-3729Item is not available in this repository.Cardiovascular (CV) morbidity and mortality is high in patients with chronic kidney disease (CKD). Most patients reveal a high prevalence of CV risk factors such as diabetes or arterial hypertension and many have manifest cardiovascular disease (CVD), such as coronary artery disease and chronic heart failure with an increased risk of clinical events including sudden cardiac death. Diabetes mellitus and hypertension contribute to the development of CKD and the prevalence of CKD is in the range of 20%-65% in diabetic and 30%-50% in hypertensive patients. Therefore, prevention and optimal treatment of CV risk factors and comorbidities are key strategies to reduce CV risk and improve survival in CKD. Beyond common CV risk factors, patients with CKD are often physically inactive and have low physical function leading to subsequent frailty with muscle fatigue and weakness, sarcopenia and increased risk of falling. Consequently, the economic health burden of CKD is high, requiring feasible strategies to counteract this vicious cycle. Regular physical activity and exercise training have been shown to be effective in improving risk factors, reducing CVD and reducing frailty and falls. Nonetheless, combining exercise training and a healthy lifestyle with pharmacological treatment is not frequently applied in clinical practice. For that reason, this Clinical Consensus Statement reviews the current literature and provides evidence-based data regarding the role of exercise training in reducing CV and overall burden in patients with CKD. The aim is to increase awareness among cardiologists, nephrologists, and health care professionals of the potential of exercise therapy in order to encourage implementation of exercise training in clinical practice, eventually reducing CV risk and disease, as well as reducing frailty in patients with CKD G3 to G5D.inpressinpres

Modeling effects of common molecular contaminants on the Euclid infrared detectors

International audienceCleanliness specifications for infrared detector arrays are usually so stringent that effects are neglibile. However, the specifications determine only the level of particulates and areal density of molecular layer on the surface, but the chemical composition of these contaminants are not specified. Here, we use a model to assess the impact on system quantum efficiency from possible contaminants that could accidentally transfer or cryopump to the detector during instrument or spacecraft testing and on orbit operation. Contaminant layers thin enough to meet typical specifications, < 0.5μgram/cm2, have a negligible effect on the net quantum efficiency of the detector, provided that the contaminant does not react with the detector surface, Performance impacts from these contaminant plating onto the surface become important for thicknesses 5 - 50μgram/cm2. Importantly, detectable change in the "ripple" of the anti reflection coating occurs at these coverages and can enhance the system quantum efficiency. This is a factor 10 less coverage for which loss from molecular absorption lines is important. Thus, should contamination be suspected during instrument test or flight, detailed modelling of the layer on the detector and response to very well known calibrations sources would be useful to determine the impact on detector performanc

How to test NISP instrument for EUCLID mission in laboratory

International audienceThe ESA mission Euclid is designed to explore the dark side of the Universe. The NISP (Near Infrared Spectro- Photometer) is one of its two instruments operating in the near-IR spectral region (0.9-2μm), that will be fully integrated and tested at Laboratory d’Astrophysique de Marseille (LAM) under vacuum and thermal conditions. The test campaign will regroup functional tests, performance tests, calibration procedure validation and observations scenario test. One of the main objectives of the test campaign will be the measurement of the focus position of NISP with respect to the EUCLID object plane. To achieve these tests campaign, a global Ground Support Equipment (GSE) called the Verification Ground System (VGS) has to be developed. It will be a complex set of GSE integrated in ERIOS chamber made of: a telescope simulator to simulate the EUCLID telescope and to inject light into NISP, a thermal environment to be used for NISP thermal balance and verification, a sets of mechanical interfaces to align all the parts into ERIOS chamber, the NISP Electrical GSE (EGSE) to control the instrument during the test and a metrology system to measure the positions of the components during the test. We will present the preliminary design and concepts of the VGS and we will show the main difficulties we have to deal with: design of thermal environment at 80K with 4mK stability, the development of a metrology system in vacuum, knowledge of the focus position within 150μm in cold, etc. The main objectives of the NISP test will be explained and how the VGS responds to the test requirement