Production of Particleboard Using Various Particle Size Hemp Shives as Filler

Research was performed into the use of hemp shive as a fast-growing and carbon-storing agricultural waste material in the production of particleboard for the construction industry. Hemp shives were acquired and prepared for board production with the use of milling and sieving to reach two target groups with 0.5 mm to 2 mm and 2 mm to 5.6 mm particle size ranges. The cold pressing method was used to produce hemp boards with Kleiberit urea formaldehyde resin as a binder. The boards were made as 19 mm thick single-layer parts with a density range of 300 ± 30 kg/m³, which qualifies them as low-density boards. Exploratory samples were made using milled hemp fibers with higher density. Additional components such as color pigments and wood finishes were added to test improved features over raw board samples. Tests were performed to determine moisture contents, density range, structural properties, and water absorption amounts. Produced board bending strength reached 2.4 MPa for the coarser particle group and thermal conductivity of 0.057 ± 0.002 W/(mK). The results were compared with existing materials used in the industry or in the development stage to indicate options of developed board applications as indoor insulation material in the construction industry.     

Beta- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain

The pro-opiomelanocortin-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH) mediates many diverse physiological actions, including anti-inflammatory and immunomodulatory effects. However, little is known about the physiological roles of the other melanocortins, beta- and gamma-MSH. Here, we investigated the effects of melanocortin peptides in an in vivo neuroinflammation model. Six hours following intracisternal (i.c.) administration of 10 microg lipopolysaccharide (LPS) to mice a five-fold increase in the nitric oxide (NO) level was seen in the animals' brains, when detected by electron paramagnetic resonance (EPR). All tested melanocortins, alpha-, beta-, gamma1- and gamma2-MSH (0.001-10 nmol/mouse i.c.), dose dependently reduced the LPS induced increases in brain NO, with an order of effectiveness: beta-MSH > or = gamma1-MSH=gamma2-MSH>alpha-MSH. Our results suggest specialized functions of beta- and gamma-MSH melanocortins in inflammatory signal modulation in the brain.     

Three Tools for the Real-Time Simulation of Embodied Spiking Neural Networks Using GPUs

This paper presents a toolbox of solutions that enable the user to construct biologically-inspired spiking neural networks with tens of thousands of neurons and millions of connections that can be simulated in real time, visualized in 3D and connected to robots and other devices. NeMo is a high performance simulator that works with a variety of neural and oscillator models and performs parallel simulations on either GPUs or multi-core processors. SpikeStream is a visualization and analysis environment that works with NeMo and can construct networks, store them in a database and visualize their activity in 3D. The iSpike library provides biologically-inspired conversion between real data and spike representations to support work with robots, such as the iCub. Each of the tools described in this paper can be used independently with other software, and they also work well together.     

Aggregation induced emission in one easy step: pyridinium AIEgens and counter ion effect

Protonation of pyridines with a strong acid is a general and straightforward approach to achieve efficient aggregation induced emission (AIE) in structurally remarkably simple organic molecules that lack any of the conventional luminophores. The relationship between the nature of counter ion and the AIE efficiency is demonstrated. The superiority of the perchlorate counter ion is attributed to efficient stabilization of the key intermolecular π⁺–π interactions between neighboring luminophore molecules in the crystal lattice.

Protonation of planar organic luminophores with perchloric acid turns on high solid state luminescence.

A large variety of optoelectronic appliances such as photovoltaic devices,¹ organic light emitting diodes,² and organic field-effect transistors³ as well as a number of light harvesting applications including artificial photosynthesis⁴ and photon refining,⁵ rely on solid state luminophores. In 2001, Tang introduced a general method to achieve highly efficient solid state luminescence (SSL) in purely organic molecules, generally known as aggregation induced emission (AIE).⁶ The vast majority of AIE luminogens (AIEgens) are based on sterically hindered, bulky propeller-like molecular structures to reduce the planarity of luminophore,⁷ because the planar architecture is known to be detrimental to the AIE efficiency.^8,7a In the meantime, the majority of luminophores with high emission intensity in solution feature a planar structure, so an approach that would allow for the design of the solid state luminogens based on the planar architecture of the known solution state emitters is highly desirable.We have recently demonstrated that the formation of intermolecular interactions between quaternary nitrogen-containing heteroaromatic cations and aromatic π-system in the solid state is a convenient and general approach to achieve AIE and to turn-on high SSL in planar organic molecules.⁹ The high SSL has been attributed to intermolecular charge transfer (ICT) between quaternary heteroaromatic subunits such as N-methyl pyridinium and N-methyl imidazolium cations and aromatic π-systems.^9b Herein we report on a further development of the conceptual approach to achieve AIE. Specifically, we demonstrate that efficient AIE can be achieved in planar organic luminophores by simple protonation of pyridine with a suitable acid (Fig. 1). Furthermore, our study provides an important insight into the relationship between the nature of counter ion and the AIE efficiency of pyridinium salts.Open in a separate windowFig. 1Effect of counter ions on AIE and SSL.The relationship between the structure of counter ion and luminescence efficiency has been studied in several pyridinium-containing AIE luminogens.¹⁰ The highest luminescence efficiency was observed for pyridinium salts possessing a counter ion that helped to avoid the detrimental aggregation-induced quenching (ACQ) effect by minimizing intermolecular π–π interactions between planar luminophore molecules (eqn (1) and (3), Fig. 1)^10a,b or by stabilizing twisted conformation of luminogens (eqn (2), Fig. 2).^10c In sharp contrast, a completely opposite counter ion effect has been observed in this study. Specifically, counter ions that contributed to strengthening the intermolecular interactions between planar pyridinium luminophores have helped to achieve the highest SSL efficiency (eqn (4), Fig. 1). Perchlorate was found to be superior as the counter-ion, whereas the corresponding mesylate, nitrate as well as halides were inferior. The latter showed apparent negative correlation between the polarizability of the counter ion and SSL emission intensity (Cl > Br > I; see eqn (4), Fig. 1.). The superiority of perchlorate has been rationalized based on X-ray crystallographic analysis as demonstrated below. The striking difference of counter-ion effects in this work (eqn (4)) and in the earlier studies (eqn (1)–(3)) points to an apparent difference in mechanisms that are responsible for the AIE (Fig. 1).Open in a separate windowFig. 2Synthesis of pyridinium salts 2a,b and 4a–f. Reagents and conditions: (a) aq. HClO₄, MeOH or MeCN, rt, 10 min, 83% (2a); 99% (4a); 32% (6). (b) 4 M HCl in dioxane, EtOAc, rt, 10 min, 97% (2b). (c) 4 M HCl in dioxane, 1 : 2 CH₂Cl₂ : hexane, rt, 10 min, 93% (4b). (d) aq. HBr, MeOH, rt, 10 min, 91% (4c). (e) aq. HI, EtOH, rt, 1 h, 61% (4d). (f) MeSO₃H, MeCN, rt, 10 min, 94% (4e). (g) HNO₃, MeCN, rt, 30 min, 99% (4f).Pyridinium salts 2a,b were obtained by protonation of commercially available 4-phenylpyridine 1 with aqueous HClO₄ and hydrochloric acid, respectively. The protonation of previously reported 3^9b with HClO₄, HCl, HBr, HI, MsOH and HNO₃ resulted in the formation of pyridinium salts 4a–f (Fig. 2). All pyridinium salts 2a,b and 4a–f were crystalline materials.UV-vis spectra of all pyridinium salts 2a,b and 4a–f and parent heteroaromatic compounds 1 and 3 were measured in MeCN solutions at room temperature under ambient atmosphere at ca. 10⁻⁵ M concentration (see ESI, pages S11–S28^†). Pyridine 1 displayed one absorption band at 251 nm (

European regulation on orphan medicinal products: 10 years of experience and future perspectives

In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products (COMP), and more than 60 orphan drugs have received marketing authorization in Europe. Here, stimulated by the tenth anniversary of the COMP, we reflect on the outcomes and experience gained in the past decade, and contemplate issues for the future, such as catalysing drug development for the large number of rare diseases that still lack effective treatments.     

Anti-diabetic effects of mildronate alone or in combination with metformin in obese Zucker rats

Mildronate is a cardioprotective drug, the mechanism of action of which is based on the regulation of l-carnitine concentration. We studied the metabolic effects of treatment with mildronate, metformin and a combination of the two in the Zucker rat model of obesity and impaired glucose tolerance. Zucker rats were p.o. treated daily with mildronate (200mg/kg), metformin (300 mg/kg), and a combination of both drugs for 4 weeks. Weight gain and plasma metabolites reflecting glucose metabolism were measured. The expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ and target genes was measured in rat heart and liver tissues. Each treatment decreased the blood glucose concentration during the fed and fasted states by 1 to 2 mmol/l. Treatment with mildronate and metformin decreased the plasma insulin concentration by 31 and 29%, respectively, while the combination of both drugs significantly reduced fed insulin concentration by about 47%. Mildronate treatment increased the expression of PPAR-α in the heart tissue and PPAR-γ in the heart and liver tissues. In addition, treatment increased the expression of PPAR target genes in the heart, but not in the liver tissue. In contrast to monotherapy, treatment with the combination of mildronate and metformin significantly decreased weight gain by 19% and did not affect food intake. In conclusion, our results demonstrate that mildronate, an inhibitor of l-carnitine biosynthesis, improves adaptation to hyperglycemia- and hyperlipidemia-induced metabolic disturbances and increases PPAR-α activity.     

Protective effects of mildronate in an experimental model of type 2 diabetes in Goto-Kakizaki rats

Background and purpose:

Mildronate [3-(2,2,2-trimethylhydrazinium) propionate] is an anti-ischaemic drug whose mechanism of action is based on its inhibition of L-carnitine biosynthesis and uptake. As L-carnitine plays a pivotal role in the balanced metabolism of fatty acids and carbohydrates, this study was carried out to investigate whether long-term mildronate treatment could influence glucose levels and prevent diabetic complications in an experimental model of type 2 diabetes in Goto-Kakizaki (GK) rats.

Experimental approach:

GK rats were treated orally with mildronate at doses of 100 and 200 mg·kg⁻¹ daily for 8 weeks. Plasma metabolites reflecting glucose and lipids, as well as fructosamine and β-hydroxybutyrate, were assessed. L-carnitine concentrations were measured by ultra performance liquid chromatography with tandem mass spectrometry. An isolated rat heart ischaemia-reperfusion model was used to investigate possible cardioprotective effects. Pain sensitivity was measured with a tail-flick latency test.

Key results:

Mildronate treatment significantly decreased L-carnitine concentrations in rat plasma and gradually decreased both the fed- and fasted-state blood glucose. Mildronate strongly inhibited fructosamine accumulation and loss of pain sensitivity and also ameliorated the enhanced contractile responsiveness of GK rat aortic rings to phenylephrine. In addition, in mildronate-treated hearts, the necrosis zone following coronary occlusion was significantly decreased by 30%.

Conclusions and implications:

These results demonstrate for the first time that in GK rats, an experimental model of type 2 diabetes, mildronate decreased L-carnitine contents and exhibited cardioprotective effects, decreased blood glucose concentrations and prevented the loss of pain sensitivity. These findings indicate that mildronate treatment could be beneficial in diabetes patients with cardiovascular problems.     

Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction

The inhibition of gamma-butyrobetaine (GBB) hydroxylase, a key enzyme in the biosynthesis of carnitine, contributes to lay ground for the cardioprotective mechanism of action of mildronate. By inhibiting the biosynthesis of carnitine, mildronate is supposed to induce the accumulation of GBB, a substrate of GBB hydroxylase. This study describes the changes in content of carnitine and GBB in rat plasma and heart tissues during long-term (28 days) treatment of mildronate [i.p. (intraperitoneal) 100 mg/kg/daily]. Obtained data show that in concert with a decrease in carnitine concentration, the administration of mildronate caused a significant increase in GBB concentration. We detected about a 5-fold increase in GBB contents in the plasma and brain and a 7-fold increase in the heart. In addition, we tested the cardioprotective effect of mildronate in isolated rat heart infarction model after 3, 7, and 14 days of administration. We found a statistically significant decrease in necrotic area of infarcted rat hearts after 14 days of treatment with mildronate. The cardioprotective effect of mildronate correlated with an increase in GBB contents. In conclusion, our study, for the first time, provides experimental evidence that the long-term administration of mildronate not only decreases free carnitine concentration, but also causes a significant increase in GBB concentration, which correlates with the cardioprotection of mildronate.