Vibration control for an experimental off-road vehicle using magnetorheological dampers

The paper presents research studies in the field of semiactive vibration control of an experimental off-road vehicle which is equipped with suspension magnetorheological (MR) dampers. Accelerometers and vehicle progressive velocity sensors are installed in body and underbody parts of the vehicle and are used in control scheme. Furthermore, IMU modules and suspension deflection sensors were used for validation of measurement part of the system. Semiactive Skyhook control algorithm, including on/off and smooth suspension MR damper control, was implemented in order to validate the control system. Quality of measurements is deteriorated by multiple factors including vehicle engine and shape of tires which was examined. Experimental results indicated better vibration suppression of vehicle body part for smooth Skyhook controller compared with passive soft and hard suspension. The presented semiactive suspension control system can be applied for complex vehicle dynamics analysis and control schemes dedicated to both the ride comfort and ride safety issues

Application of targeted 2D planar chromatography in the control of ginkgolic acids in some herbal drugs and dietary supplements

Two-step targeted 2D planar chromatographic method (2D-TLC) was used in the determination of ginkgolic acids in pharmaceuticals and dietary supplements. The choice of the extraction method and the separation technique was guided by the formulation type (capsule, tablet, tincture) with expected low amounts of ginkgolic acids in the analyzed herbal samples. Separation of ginkgolic acids C15:1 and C17:1 on HPTLC RP18 WF254s was preceded by its separation from the sample matrix on TLC Si60 F254s. Mobile phases consisted of acetonitrile/water/formic acid (80:20:1, V/V/V) and n-heptane/ethyl acetate/formic acid (20:30:1, V/V/V), resp. Identification of separated compounds was based on 2D-TLC co-chromatography with reference substances and off-line 2D-TLC x HPLC-DAD-ESI-MS analysis. Quantification of ginkgolic acids C15:1 and C17:1 was conducted densitometrically. Among the analyzed products, the presence of ginkgolic acids was confirmed only in herbal drugs containing 60 % ethanolic tinctures of Ginkgo biloba leaves. The use of TLC in the quantification of ginkgolic acids C15:1 and C17:1 in ginkgo extracts was described for the first time

HPTLC determination of diosgenin in fenugreek seeds

A new HPTLC-densitometric method for diosgenin determination in fenugreek seeds was established after optimization of the conditions for efficient saponin extraction and acid hydrolysis. Several procedures were tested, the best of which was a three-step Soxhlet extraction, followed by hydrolysis of the obtained methanolic extract with 2 mol L–1 H2SO4. Best diosgenin separation from other hydrolysis products was obtained on HPTLC Si60F254 plates using a mixture of n-heptane/ethyl acetate (7:3, V/V) and modified anisaldehyde as a spraying reagent. The method was preliminarily validated and the determined amounts of diosgenin in fenugreek seeds of Polish and African origin were found to be similar and ranged from 0.12–0.18 %

TLC determination of some flavanones in the buds of different genus Populus species and hybrids

Flavonoids in the buds of eight Populus species and hybrids were detected and compared with the aid of an optimized TLC method. Separation of 17 flavonoid aglycones belonging to different groups, namely, flavones, flavonols, flavanones and flavanonols, previously described as constituents of poplar buds, was performed on silica gel plates using a hexane/ethyl acetate/formic acid (60:40:1.3, V/V/V) mixture as the mobile phase. Pinocembrin and pinostrobin were found in the majority of analyzed poplar buds. For quantitative analysis of both compounds, two TLC evaluation modes, densitometric and videodensitometric, were compared and the established methods were validated. Concentrations of flavanones in some extracts differed slightly or significantly due to the analyzed plant matrix complexity and the TLC evaluation mode applied. Poplar buds rich in flavanones originated from P. canadensis ‘Robusta’ (1.82 and 2.23 g per 100 g, resp.) and P. balsamifera (1.17 and 2.24 g per 100 g, resp.)

Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia

Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb

Non-PEGylated liposomes for convection-enhanced delivery of topotecan and gadodiamide in malignant glioma: initial experience

Convection-enhanced delivery (CED) of highly stable PEGylated liposomes encapsulating chemotherapeutic drugs has previously been effective against malignant glioma xenografts. We have developed a novel, convectable non-PEGylated liposomal formulation that can be used to encapsulate both the topoisomerase I inhibitor topotecan (topoCED™) and paramagnetic gadodiamide (gadoCED™), providing an ideal basis for real-time monitoring of drug distribution. Tissue retention of topoCED following single CED administration was significantly improved relative to free topotecan. At a dose of 10 μg (0.5 mg/ml), topoCED had a half-life in brain of approximately 1 day and increased the area under the concentration–time curve (AUC) by 28-fold over free topotecan (153.8 vs. 5.5 μg day/g). The combination of topoCED and gadoCED was found to co-convect well in both naïve rat brain and malignant glioma xenografts (correlation coefficients 0.97–0.99). In a U87MG cell assay, the 50% inhibitory concentration (IC50) of topoCED was approximately 0.8 μM at 48 and 72 h; its concentration–time curves were similar to free topotecan and unaffected by gadoCED. In a U87MG intracranial rat xenograft model, a two-dose CED regimen of topoCED co-infused with gadoCED greatly increased median overall survival at dose levels of 0.5 mg/ml (29.5 days) and 1.0 mg/ml (33.0 days) vs. control (20.0 days; P < 0.0001 for both comparisons). TopoCED at higher concentrations (1.6 mg/ml) co-infused with gadoCED showed no evidence of histopathological changes attributable to either agent. The positive results of tissue pharmacokinetics, co-convection, cytotoxicity, efficacy, and lack of toxicity of topoCED in a clinically meaningful dose range, combined with an ideal matched-liposome paramagnetic agent, gadoCED, implicates further clinical applications of this therapy in the treatment of malignant glioma

Over 200,000 kilometers of free-flowing river habitat in Europe is altered due to impoundments

European rivers are disconnected by more than one million man-made barriers that physically limit aquatic species migration and contribute to modification of freshwater habitats. Here, a Conceptual Habitat Alteration Model for Ponding is developed to aid in evaluating the effects of impoundments on fish habitats. Fish communities present in rivers with low human impact and their broad environmental settings enable classification of European rivers into 15 macrohabitat types. These classifications, together with the estimated fish sensitivity to alteration of their habitat are used for assessing the impacts of six main barrier types (dams, weirs, sluices, culverts, fords, and ramps). Our results indicate that over 200,000 km or 10% of previously free-flowing river habitat has been altered due to impoundments. Although they appear less frequently, dams, weirs and sluices cause much more habitat alteration than the other types. Their impact is regionally diverse, which is a function of barrier height, type and density, as well as biogeographical location. This work allows us to foresee what potential environmental gain or loss can be expected with planned barrier management actions in rivers, and to prioritize management actions

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Identification of Control-Related Signal Path for Semi-Active Vehicle Suspension with Magnetorheological Dampers

This paper presents a method for the identification of control-related signal paths dedicated to a semi-active suspension with MR (magnetorheological) dampers, which are installed in place of standard shock absorbers. The main challenge comes from the fact that the semi-active suspension needs to be simultaneously subjected to road-induced excitation and electric currents supplied to the suspension MR dampers, while a response signal needs to be decomposed into road-related and control-related components. During experiments, the front wheels of an all-terrain vehicle were subjected to sinusoidal vibration excitation at a frequency equal to 12 Hz using a dedicated diagnostic station and specialised mechanical exciters. The harmonic type of road-related excitation allowed for its straightforward filtering from identification signals. Additionally, front suspension MR dampers were controlled using a wideband random signal with a 25 Hz bandwidth, different realisations, and several configurations, which differed in the average values and deviations of control currents. The simultaneous control of the right and left suspension MR dampers made it necessary to decompose the vehicle vibration response, i.e., the front vehicle body acceleration signal, into components related to the forces generated by different MR dampers. Measurement signals used for identification were taken from numerous sensors available in the vehicle, e.g., accelerometers, suspension force and deflection sensors, and sensors of electric currents, which control the instantaneous damping parameters of MR dampers. The final identification was carried out for control-related models evaluated in the frequency domain and revealed several resonances of the vehicle response and their dependence on the configurations of control currents. In addition, the parameters of the vehicle model with MR dampers and the diagnostic station were estimated based on the identification results. The analysis of the simulation results of the implemented vehicle model carried out in the frequency domain showed the influence of the vehicle load on the absolute values and phase shifts of control-related signal paths. The potential future application of the identified models lies in the synthesis and implementation of adaptive suspension control algorithms such as FxLMS (filtered-x least mean square). Adaptive vehicle suspensions are especially preferred for their ability to quickly adapt to varying road conditions and vehicle parameters