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In the Netherlands, the functional approach described in the 2008 European Asphalt Concrete standards was selected, specifying mixtures by their stiffness, fatigue resistance, permanent deformation, moisture sensitivity and limited composition data. The requirements for the functional specifications were based on the existing experience with a large number of mixes. Since the introduction of the standards, unexpected developments like improved performance in all functional tests with increasing RAP content, led to questions about the predictive quality of the laboratory determined functional characteristics for field performance and the potential causes of a mis-match between lab and practice. These questions led to a large, long term project in the Netherlands (NL-LAB) in which the functional characteristics are determined in the process of construction projects. They are determined on (I) material mixed and compacted in the lab, (II) mixed in the plant and compacted in the lab and (III) mixed in the plant and compacted in the road. These tests will eventually provide insight in the effect of mixing and compaction. The pavement sections are monitored in time, to allow the link with pavement performance. The sections will be sampled during their service life to see changes occur in their functional properties. For the road industry, that tries to guarantee pavement performance by accurate selection of materials, the possibility of design information based on both laboratory and in situ results would be beneficial.Two mixes for base layers with different mix compositions and amounts of RAP are analysed using formalistic expressions originating from Design Guide Level II for estimation of various performance indicators. This project uses expressions to analyse the differences between the mixes in the three cases described above. It addresses the possibility of utilizing these expressions during preliminary mix design to guide the selection of mix composition parameters towards a desired optimum.

Sinds 2008 werken we in Nederland met functionele eigenschappen voor asfaltbeton. Hierbij wordt niet zo zeer op het “recept” van het asfalt gestuurd, alswel op de eigenschappen ervan die van belang zijn voor het gedrag in de weg.Binnen het NL-LAB programma wordt de relatie tussen deze functioneleeigenschappen en het gedrag in de weg gevalideerd. Hierbij wordt ookgekeken naar de invloed van mengen en verdichten op de functioneleeigenschappen. Binnen dit programma is er voor de eerste twee projectengekeken naar de relatie tussen de mengselsamenstelling en de indirectetreksterkte en weerstand tegen permanente vervorming. Dergelijke relaties zijnin de historie van de wegenbouw vaker met succes gebruikt. Veranderingen inproeven, materialen, mengselsamenstelling en gebruikscondities vragen echterom validatie en calibratie. Het meest recente stelsel van relaties tussensamenstelling en functionele eigenschappen is dat van de MechanisticEmpirical Design Guide. In deze bijdrage wordt beschreven hoe deze relatieworden gebruikt als uitgangspunt voor het koppelen van mengselsamenstellingvan twee AC mengsels aan de indirecte treksterkte (ongeconditioneerd) en deweerstand tegen permanente vervorming. Hierbij wordt ook gekeken of heteffect van mengen en verdichten zichtbaar is in de data.

One of the most fascinating aspects of the field of epigenetics is the emerging ability of environmental factors to trigger epigenetic changes in eukaryotic cells, thus contributing to transient or stable, and potentially heritable, changes in gene expression program in the absence of alteration in DNA sequence. Epigenetic response may result in cell adaptation to environmental stimuli or, in some instances, may contribute to generation or progression of different kind of diseases. A paradigmatic case of disease that is accompanied by multiple epigenetic alterations is gastric cancer, among other relevant examples. In turn, Helicobacter pylori (Hp) infection has been associated as a leading cause of gastric cancer. One possible hypothesis is that Hp-gastric cell interaction initiates an epigenetic reprogramming of host cell genome that may favor tumorigenesis. Accordingly, an abundance of experimental evidence indicates that several epigenetic alterations underlie the gastric cancerogenesis process and that these alterations represent one of the major hallmarks of gastric cancer. However, several critical questions remain unanswered: Does Hp directly provoke epigenetic alterations? Which mechanisms underlie these phenomena? Based on currently available data, it is often arduous to discriminate between the epigenetic modifications directly triggered by Hp-gastric cell interaction and those alterations that are mediated by inflammation process or by many other molecular and genetic events occurring during the gastric cancer progression. We will review our present knowledge of epigenetic modifications and alterations proven to occur in host cells as a direct consequence of Hp infection.

Since the occurrence of West Nile virus (WNV) infection in humans in 2008 in Italy, concerns have been raised about the potential risks associated with solid organ transplantation (SOT). A nationwide retrospective survey showed that 1.2% of SOT donors in 2009 were WNV-seropositive and demonstrated that human WNV infection is distributed throughout several Italian regions. Transmission of WNV or other arboviruses through SOT is a possibility and risk assessment should be carried out before SOT to avoid infection through transplantation.

Nowadays, oral oil extracts of Cannabis represent the most relevant galenic plant-derived formulations employed in clinics. Nevertheless, the low and variable Delta 9-tetrahydrocannabinol (THC) oral bioavailability due to hepatic first-pass metabolism and low solubility in biological fluids makes Cannabis pharmacological response highly unpredictable. In this scenario, new formulation strategies appear crucial to improve cannabinoids bioavail-ability and stability, administration comfort and patient compliance. Here, we present a nanoemulsion (NE) for the buccal administration of olive oil extract from a Cannabis sativa L. variety (Bedrocan (R)). A preliminary study was carried out on olive oil-based NE to identify the optimal formulation conditions to achieve a stable system. The Bedrocan (R)-loaded NE were then prepared and characterized for size, polydispersity index, stability upon delivery by the common buccal nebulizers.THC content and release in simulated buccal fluids and permeation studies across porcine buccal mucosa. The Bedrocan (R) NEs ensured THC stability and solubility in the buccal medium as compared with the Cannabis oil extract. Furthermore, the nanoemulsification process led to a THC diffusion and absorption on buccal mucosa 20-folds and 2-folds higher than olive oil extract, respectively. Overall, the results suggest that Bedrocan (R) NE represents a novel formulation strategy for the buccal administration of Cannabis extracts that can overcome the limits associated with conventional oily formulations.

Ischemia-reperfusion injury, a clinical problem during cardiac surgery, involves worsened adenosine trisphosphate (ATP) generation and damage to the heart. We studied carbon monoxide ( CO) pretreatment, proven valuable in rodents but not previously tested in large animals, for its effects on pig hearts subjected to cardiopulmonary bypass with cardioplegic arrest. Hearts of CO-treated pigs showed significantly higher ATP and phosphocreatine levels, less interstitial edema, and apoptosis of cardiomyocytes and required fewer defibrillations after bypass. We conclude that treatment with CO improves the energy status, prevents edema formation and apoptosis, and facilitates recovery in a clinically relevant model of cardiopulmonary bypass surgery.

Hand hygiene, social distancing, and face covering are considered the first protection against Coronavirus spreading. The high demand during the COVID-19 emergency has driven a frenetic production and marketing of hand sanitizer gels. Nevertheless, the effect of the gelling agent and its amount on the effectiveness of alcohol-based hand sanitizers (ABHSs) needs to be clarified. We presented a systematic study on the effect of the characteristics and concentration of the most employed excipients on the properties and antimicrobial activity of ABHSs. Three different gelling agents, carbopol, hydroxypropylmethylcellulose (HPMC), and hydroxyethylcellulose (HEC), at four different concentrations were used to prepare ABHSs. Viscosity, spreadability, delivery from commercial dispensers, evaporation rate, rubbing time, and hand distribution of the ABHSs were then explored. Biocidal activity of selected ABHSs was evaluated in vitro on ATCC and clinical strains. The studied ABHS can be considered bioactive and comfortable. Nevertheless, the cellulose polymers and ethanol interactions led to a slight but significant reduction in the biocidal activity compared with carbopol-based formulations. Our results underline the importance of the gelling agent properties and support the choice of carbopol as one of the best thickener agents in ABHS formulations.

0 RTHOTOPIC liver transplantation (OLT) is the only clinically effective treatment for fulminant or chronic liver failure, whether genetic in origin or due to acquired hepatocellular dysfunction. However, wider application of OLT is limited by organ shortage and a relatively high mortality rate. Consequently, there is increasing interest in hepatocyte transplantation, especially in the treatment of metabolic disorders, or, in combination with plasmapheresis, of fulminant hepatic failure (bioartificial liver).’ With genetic defects, it may be possible to introduce genes into hepatocytes before autotransplantation. In recent years, the spleen has been the most popular site for inoculation of hepatocytes in experimental studies. Several authors have reported good survival and function,‘.” but problems remain in respect to long-term survival, ccl1 proliferation and differentiation, and the provision of sufficient number of cells to support failing liver function. Additionally, with one exception,4 most studies have been performed in the rat, and there has been little work carried out in large mammals. In order to address these concerns, we describe a method of autotransplantation in the pig which simplifies the surgical procedures and allows estimation of hepatocyte proliferation and survival in the spleen.

Background Programmed epigenetic modifications occurring at early postnatal brain developmental stages may have a long-lasting impact on brain function and complex behavior throughout life. Notably, it is now emerging that several genes that undergo perinatal changes in DNA methylation are associated with neuropsychiatric disorders. In this context, we envisaged that epigenetic modifications during the perinatal period may potentially drive essential changes in the genes regulating brain levels of critical neuromodulators such as d-serine and d-aspartate. Dysfunction of this fine regulation may contribute to the genesis of schizophrenia or other mental disorders, in which altered levels of d-amino acids are found. We recently demonstrated that Ddo, the d-aspartate degradation gene, is actively demethylated to ultimately reduce d-aspartate levels. However, the role of epigenetics as a mechanism driving the regulation of appropriate d-ser levels during brain development has been poorly investigated to date. Methods We performed comprehensive ultradeep DNA methylation and hydroxymethylation profiling along with mRNA expression and HPLC-based d-amino acids level analyses of genes controlling the mammalian brain levels of d-serine and d-aspartate. DNA methylation changes occurring in specific cerebellar cell types were also investigated. We conducted high coverage targeted bisulfite sequencing by next-generation sequencing and single-molecule bioinformatic analysis. Results We report consistent spatiotemporal modifications occurring at the Dao gene during neonatal development in a specific brain region (the cerebellum) and within specific cell types (astrocytes) for the first time. Dynamic demethylation at two specific CpG sites located just downstream of the transcription start site was sufficient to strongly activate the Dao gene, ultimately promoting the complete physiological degradation of cerebellar d-serine a few days after mouse birth. High amount of 5′-hydroxymethylcytosine, exclusively detected at relevant CpG sites, strongly evoked the occurrence of an active demethylation process. Conclusion The present investigation demonstrates that robust and selective demethylation of two CpG sites is associated with postnatal activation of the Dao gene and consequent removal of d-serine within the mouse cerebellum. A single-molecule methylation approach applied at the Dao locus promises to identify different cell-type compositions and functions in different brain areas and developmental stages.