An Evaluation of the Effect of Ultrasonic Degassing on Components Produced by High Pressure Die Casting

Ultrasonic treatment is known to be efficient for aluminium melt degassing with the additional benefits of being both economical and environment friendly. This paper describes the effect of ultrasonic degassing on the preparation of an AlSi9Cu3(Fe) alloy for High Pressure Die Casting (HPDC). The degassing efficiency was assessed in terms of the indirect evaluation of the melt, by means of the reduced pressure test and the porosity evaluation of the cast parts. Additionally, the corresponding hydrogen content was estimated with an experimental equation reported in the literature. Ultrasonic degassing shows greater efficiency in terms of hydrogen removal from the melt than conventional N2 + Ar lance bubbling. Components produced by HPDC without degassing, with ultrasonic degassing and with lance degassing, were analysed by computed tomography and by metallography. The results show that the components produced by HPDC after ultrasonic degassing have a similar porosity level to components degassed with conventional lance bubbling, both showing an important improvement over components produced without degassing treatment. Hardness values were similar for all different treatment conditions and well over the minimum value established for the alloy by the corresponding standard

Comparative Life Cycle Assessment of Green Sand Casting and Low Pressure Die Casting for the production of self-cleaning AlMg3-TiO2 Metal Matrix Composite

The growth in the use of novel materials, as it is the case of the Metal Matrix Composites (MMCs), is producing a positive impact in production processes, allowing to obtain final products with improved functionalities, such as an increase of the strength-to-weight ratio, or enhancement of the mechanical properties of the material, minimizing as well the environmental impacts and production costs without compromising the required technical properties. To determine and compare the environmental impact of different processes employing these materials, this paper provides a comparative analysis of the Life Cycle Assessment (LCA), under ISO 14040:2006 framework and European ILCD guidelines, of two different manufacturing technologies, Green Sand Casting (GSC) and Low Pressure Die Casting (LPDC), for the particular case of a self-cleaning doorknob, produced by an aluminium alloy reinforced with hard TiO2 nanoparticles, that confers special characteristics to the composite, such as an increase of the hardness value and tensile strength, a high wear resistance, a good chemical stability, and antibacterial properties. The results show a slight difference between both technologies in terms of kg CO2 eq. emitted, with just a 3,16 % variation, where GSC emissions are 13,098 kg, whereas 12,684 kg are released from LPDC. In addition, an economic analysis was performed, showing a 17 % cost reduction in case of LPDC. This study presents for the first time a comparative Life Cycle Assessment of GSC and LPDC, when employing new nanocomposite materials, contributing with novel datasets and meaningful insights to improve the state of the art in the field, serving as well as a support for manufacturers in decision making process involving the use of these technologies.This research has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 826312) in the context of the LightMe project. It has also received funds from Board of Education of Junta de Castilla y León and the European Social Fund (EDU/1508/2020). The authors want to acknowledge the support of ÖGI (Österreichisches Gießerei-Institut) for the data about processes

Effects of Atrial Fibrillation on the Human Ventricle

Rationale: Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. Objective: This study investigates the effects and molecular mechanisms of AF on the human LV. Methods and Results: Ventricular myocardium from patients with aortic stenosis and preserved LV function with sinus rhythm or rate-controlled AF was studied. LV myocardium from patients with sinus rhythm and patients with AF showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude of LV cardiomyocytes was reduced in patients with AF, while diastolic Ca2+ levels and Ca2+ transient kinetics were not statistically different. These results were confirmed in LV cardiomyocytes from nonfailing donors with sinus rhythm or AF. Moreover, normofrequent AF was simulated in vitro using arrhythmic or rhythmic pacing (both at 60 bpm). After 24 hours of AF-simulation, human LV cardiomyocytes from nonfailing donors showed an impaired Ca2+ transient amplitude. For a standardized investigation of AF-simulation, human iPSC-cardiomyocytes were tested. Seven days of AF-simulation caused reduced systolic Ca2+ transient amplitude and sarcoplasmic reticulum Ca2+ load likely because of an increased diastolic sarcoplasmic reticulum Ca2+ leak. Moreover, cytosolic Na+ concentration was elevated and action potential duration was prolonged after AF-simulation. We detected an increased late Na+ current as a potential trigger for the detrimentally altered Ca2+/Na+-interplay. Mechanistically, reactive oxygen species were higher in the LV of patients with AF. CaMKII (Ca2+/calmodulin-dependent protein kinase IIδc) was found to be more oxidized at Met281/282 in the LV of patients with AF leading to an increased CaMKII activity and consequent increased RyR2 phosphorylation. CaMKII inhibition and ROS scavenging ameliorated impaired systolic Ca2+ handling after AF-simulation. Conclusions: AF causes distinct functional and molecular remodeling of the human LV. This translational study provides the first mechanistic characterization and the potential negative impact of AF in the absence of tachycardia on the human ventricle

Marine Drugs from Sponge-Microbe Association—A Review

The subject of this review is the biodiversity of marine sponges and associated microbes which have been reported to produce therapeutically important compounds, along with the contextual information on their geographic distribution. Class Demospongiae and the orders Halichondrida, Poecilosclerida and Dictyoceratida are the richest sources of these compounds. Among the microbial associates, members of the bacterial phylum Actinobacteria and fungal division Ascomycota have been identified to be the dominant producers of therapeutics. Though the number of bacterial associates outnumber the fungal associates, the documented potential of fungi to produce clinically active compounds is currently more important than that of bacteria. Interestingly, production of a few identical compounds by entirely different host-microbial associations has been detected in both terrestrial and marine environments. In the Demospongiae, microbial association is highly specific and so to the production of compounds. Besides, persistent production of bioactive compounds has also been encountered in highly specific host-symbiont associations. Though spatial and temporal variations are known to have a marked effect on the quality and quantity of bioactive compounds, only a few studies have covered these dimensions. The need to augment production of these compounds through tissue culture and mariculture has also been stressed. The reviewed database of these compounds is available at www.niobioinformatics.in/drug.php

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Fractal characterization of pharmaceutical bulk solid surfaces

Schüttgüter in Form von Pulvern oder Granulaten stellen sowohl eigenständige Arzneiformen als auch häufige Zwischenprodukte bei der Arzneimittelherstellung dar. Um die Einheitlichkeit der Dosierung zu gewährleisten, ist die Fließfähigkeit als eines der zentralen Qualitätsmerkmale anzusehen. In der vorliegenden Arbeit wurde die Veränderung der fraktalen Dimension D der Partikeloberflächen in binären Mischungen von α-Lactose-Monohydrat (GranuLac® 200) und hydrophilem hochdispersem Sili-ciumdioxid (Aerosil® 200) in Abhängigkeit von der Mischzeit untersucht. Hierbei kamen sowohl die Ras-terkraftmikroskopie als auch verschiedene Adsorptionsmethoden zur Anwendung. Ziel war es, die prin-zipielle Durchführbarkeit der beschriebenen Techniken sowie deren Anwendbarkeit auf das vorliegende Modellsystem zu prüfen und die ggf. bestehende Korrelation zwischen D und den Ergebnissen der Zug-spannungstests aufzuzeigen.Bulk solids like powders or granulates are dosage forms of their own as well as regular intermediates in pharmaceutical production. Flowability is considered a key prerequisite for uniformity of dosage. In the survey reported here the effect of blending time on particle surface fractal dimension D of binary mixtures of α-lactose monohydrate (GranuLac® 200) and hydrophilic highly dispersible silicon dioxide (Aerosil® 200) was investigated by use of atomic force microscopy as well as several adsorption tech-niques. Aim of the study was to test the described methods for applicability to the current model and to identify the correlation between D and the tensile strength, if any

Effects of atrial fibrillation on the human ventricle

Rationale: Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. Objective: This study investigates the effects and molecular mechanisms of AF on the human LV. Methods and results: Ventricular myocardium from patients with aortic stenosis and preserved LV function with sinus rhythm or rate-controlled AF was studied. LV myocardium from patients with sinus rhythm and patients with AF showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude of LV cardiomyocytes was reduced in patients with AF, while diastolic Ca2+ levels and Ca2+ transient kinetics were not statistically different. These results were confirmed in LV cardiomyocytes from nonfailing donors with sinus rhythm or AF. Moreover, normofrequent AF was simulated in vitro using arrhythmic or rhythmic pacing (both at 60 bpm). After 24 hours of AF-simulation, human LV cardiomyocytes from nonfailing donors showed an impaired Ca2+ transient amplitude. For a standardized investigation of AF-simulation, human iPSC-cardiomyocytes were tested. Seven days of AF-simulation caused reduced systolic Ca2+ transient amplitude and sarcoplasmic reticulum Ca2+ load likely because of an increased diastolic sarcoplasmic reticulum Ca2+ leak. Moreover, cytosolic Na+ concentration was elevated and action potential duration was prolonged after AF-simulation. We detected an increased late Na+ current as a potential trigger for the detrimentally altered Ca2+/Na+-interplay. Mechanistically, reactive oxygen species were higher in the LV of patients with AF. CaMKII (Ca2+/calmodulin-dependent protein kinase IIδc) was found to be more oxidized at Met281/282 in the LV of patients with AF leading to an increased CaMKII activity and consequent increased RyR2 phosphorylation. CaMKII inhibition and ROS scavenging ameliorated impaired systolic Ca2+ handling after AF-simulation. Conclusions: AF causes distinct functional and molecular remodeling of the human LV. This translational study provides the first mechanistic characterization and the potential negative impact of AF in the absence of tachycardia on the human ventricle

Concept for the Evaluation of Carcinogenic Substances in Population-Based Human Biomonitoring

The Human Biomonitoring (HBM) Commission at the German Environment Agency holds the opinion that for environmental carcinogens for which no exposure levels can be assumed and are harmless to health, health-based guidance values corresponding to the classical definition of the HBM-I or HBM-II value cannot be established. Therefore, only reference values have been derived so far for genotoxic carcinogens from exposure data of the general population or subpopulations. The concept presented here opens up the possibility of performing health risk assessments of carcinogenic substances in human biomonitoring, and thus goes decisively beyond the purely descriptive statistical reference value concept. Using the presented method, quantitative dose descriptors of internal exposure can be derived from those of external exposure, provided that sufficient toxicokinetic information is available. Dose descriptors of internal exposure then allow the simple estimate of additional lifetime cancer risks for measured biomarker concentrations or, conversely, of equivalent concentrations for selected risks, such as those considered as tolerable for the general population. HBM data of chronic exposures to genotoxic carcinogens can thus be used to assess the additional lifetime cancer risk referring to the general population and to justify and prioritize risk management measures

Development of New Photoswitchable Azobenzene Based γ‑Aminobutyric Acid (GABA) Uptake Inhibitors with Distinctly Enhanced Potency upon Photoactivation

A series of nipecotic acid derivatives with new azo benzene based photoswitchable N-substituents was synthesized and characterized in their (<i>E</i>)- and (<i>Z</i>)-form for their functional inhibitory activity at γ-aminobutyric acid transporters subtype 1 (GAT1), the most common γ-aminobutyric acid (GABA) transporter subtype in the central nervous system (CNS). This led to the identification of the first photoswitchable ligands exhibiting a moderate uptake inhibition of GABA in their (<i>E</i>)- but distinctive higher inhibitory potency in their (<i>Z</i>)-form resulting from photoirradiation. For the most efficient photoactivatable nipecotic acid derivative displaying an <i>N</i>-but-3-yn-1-yl linker with a terminal diphenyldiazene unit, an inhibitory potency of 4.65 ± 0.05 (pIC₅₀) was found for its (<i>E</i>)-form. which increased by almost two log units up to 6.38 ± 0.04 when irradiated. The effect of this photoswitchable mGAT1 inhibitor has also been evaluated and confirmed in patch-clamp recordings in acute hippocampal slices from mice