The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

Tofisopam is a member of the 2,3-benzodiazepine compound family which is marketed for the treatment of anxiety in some European countries. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. In addition to anxiolytic properties, antipsychotic effects are reported. We now show that tofisopam, 50 mg/kg intraperitoneally (i.p.), administered in parallel to repeated doses of dizocilpine 0.2 mg/kg i.p. can ameliorate dizocilpine-induced prolongation of immobility, which is considered to be a model of negative symptoms of psychosis. We further show that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with highest affinity to PDE-4A1 (0.42 μM) followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM) and PDE-2A3 (2.11 μM). The data indicate that tofisopam is an interesting candidate for the adjuvant treatment of psychosis with focus on negative symptoms. Combined partial inhibition of PDE-4 and PDE-10 as well as PDE-2 may be the underlying mechanism to this activity. Due to the good safety profile of tofisopam as evident from long-term use of this agent in patients, it may be concluded that dual or triple inhibition of PDE isoenzymes with additive or synergistic effects may be an interesting approach to pharmacological activity, resulting in active compounds with beneficial safety profile. Dose-limiting side effects such as emesis induced by selective inhibition of PDE-4 may be prevented by such strategies

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.Peer reviewe

Timing belt in power transmission and conveying system

This paper presents the problem of phenomena occurring at the contact of a timing belt and a pulley. Depending on a belt size range these phenomena differ significantly. There is no indication as to what solutions are optimal for drive belts. The analysis of the coupling process and performance tests have shown that the drive belt should have a cord of very good mechanical properties and its raceway side should be made from the material of a low friction coefficient against the pulley material. A flat belt in power transmission and conveying systems cooperates with several elements consisting of timing pulleys, tensioners or guiding rails. In gear with timing belts they depend strongly on characteristics of the process as well as the type of friction. In recent constructions, producers of timing belts are very much concerned about achieving as much slippery surface as possible. The work describes the problem of friction on different surfaces as well as its influence on gear lifetime. Research results confirm that on many surfaces bigger coefficient of friction is expected

Timing belt in power transmission and conveying system

This paper presents the problem of phenomena occurring at the contact of a timing belt and a pulley. Depending on a belt size range these phenomena differ significantly. There is no indication as to what solutions are optimal for drive belts. The analysis of the coupling process and performance tests have shown that the drive belt should have a cord of very good mechanical properties and its raceway side should be made from the material of a low friction coefficient against the pulley material. A flat belt in power transmission and conveying systems cooperates with several elements consisting of timing pulleys, tensioners or guiding rails. In gear with timing belts they depend strongly on characteristics of the process as well as the type of friction. In recent constructions, producers of timing belts are very much concerned about achieving as much slippery surface as possible. The work describes the problem of friction on different surfaces as well as its influence on gear lifetime. Research results confirm that on many surfaces bigger coefficient of friction is expected

Selecting a Flat Belts for the Model of Coupling with Flat Belts

Mechanical gears with flat belts are currently the most intensively developing group of mechanical transmissions. This is due to the need to increase the speed of moving elements of machines and to transfer torque over considerable distances. This intensive development has enabled the development of materials engineering and the emergence of modern materials in the production of belts. An example would be the use of Kevlar and modern Carbon fibers. Analysis of the latest flat belt designs against the background of the whole group of these gears allows to indicate how to choose a belt for the gear so that coupling with the wheel is optimal. For this purpose, the model of coupling was analyzed again for modern drive. Modeling of this process is a solution to the age-old problem of choosing the right belt for a belt transmission

Development trends in belt transmissions with V-belt

The continuous increase in the use of the transmissions with V-belt, the introduction of new materials for the production of belts and the development of new manufacturing techniques have become the reason for undertaking research works on the possibilities of increasing the load capacity and durability of belts as well as reducing their influence on the environment. It is important to know the latest mechanical and rheological characteristics of the belts in terms of their strength characteristics and fulfilment of the conditions for the correct operation of the transmission. The results of these works will make it possible to determine the scope of applicability of these belts in propulsion and transport technology as well as to develop new geometrical forms of pulleys and V-belts

The application of the optical system ATOS II for rapid prototyping methods of non-classical models of cogbelt pulleys

The widespread application of both gear wheels and cogbelt pulleys with noncircular generating line in technique stimulates the development of manufacturing and measuring methods of these wheels. The paper presents the rapid prototyping methods of models of cogbelt pulleys with nocircular evelope. Evaluation method of manufacturing accuracy of cogbelt pulleys, which are applied in unevenrunning belt transmissions, are presented. These transmissions are widely applied in steering techniques and drives of machines and devices. Verification of mapping accuracy of shape of geometrical model of cogbelt pulley was done with the application of noncontact optical system i.e. coordinate optical scanner GOM Atos Compact Scan 5M GOM company

The application of the optical system ATOS II for rapid prototyping methods of non-classical models of cogbelt pulleys

The widespread application of both gear wheels and cogbelt pulleys with noncircular generating line in technique stimulates the development of manufacturing and measuring methods of these wheels. The paper presents the rapid prototyping methods of models of cogbelt pulleys with nocircular evelope. Evaluation method of manufacturing accuracy of cogbelt pulleys, which are applied in unevenrunning belt transmissions, are presented. These transmissions are widely applied in steering techniques and drives of machines and devices. Verification of mapping accuracy of shape of geometrical model of cogbelt pulley was done with the application of noncontact optical system i.e. coordinate optical scanner GOM Atos Compact Scan 5M GOM company

Behavioral and Biochemical Effects of Glyphosate-Based Herbicide Roundup on Unionid Mussels: Are Mussels Good Indicators of Water Pollution with Glyphosate-Based Pesticides?

The behavioral (filtration activity) and biochemical (oxidative stress) effects of Roundup 360 Plus (active substance glyphosate) herbicide on two species of unionid mussels, Unio tumidus (Philipsson, 1788) and Anodonta anatina (L.), were evaluated at concentrations ranging from 15 to 1500 μg L−1 of glyphosate for five days. During all experiments, we did not record the mortality of the studied mussel species. Exposure to Roundup herbicide induced dose-dependent filtration disruptions in both U. tumidus and A. anatina. Exposure of the mussels to a low and environmentally relevant concentration 15 µg glyphosate L−1 resulted in a slight (<20%) and temporary decrease in mean valve dilation. Exposure of the mussels to Roundup at relatively high concentrations caused drastic and prolonged shell closure and a reduction in the mussel shell opening rate. Exposure of both mussel species to herbicide resulted in oxidative stress; an increase in superoxide dismutase enzymatic activity was detected. The most significant increase in SOD activity was observed after the exposure to the highest Roundup concentration. However, no correlation between the Roundup concentration and enzymatic activity was found. The use of unionid mussels to detect environmentally relevant concentrations of Roundup, as a part of biological early warning system for pollution, is limited, but they can serve to detect the incidental pollution of aquatic ecosystems with high concentrations of this herbicide

Influence of extruder plasticizing systems on the selected properties of pla/graphite composite

Twin-screw extrusion is a crucial method for the direct inserting of carbon micro- and nanomaterials into a polymer matrix using a dry procedure. The study aimed to determine the influence of the parameters of the twin-screw extruder plasticizing system on the dispersion homogeneity and distribution of graphite filler in the polylactide polymer matrix and overall quality of the composite. As a filler, a graphite micropowder with a 5 μm lateral size of platelets was used at concentration of 1 wt.%. Three configurations of screws with different mixing intensity and various types segments were considered in the extrusion experiments. Morphology and chemical structure of the obtained composites were examined using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy – attenuated total reflectance (FTIR-ATR) and Raman spectroscopy. Differential scanning calorimetry (DSC) and melting flow rate measurements (MFR) were used to asses thermal and rheological properties of the composites. Samples of the polylactide/graphite composites were also subjected to mechanical tests. The results show that the selection of the mechanical parameters of twin-screw extruder plasticizing system plays a key role in the preparation of the homogeneous PLA/graphite composites. Incorrect selection of the screw geometry results in poor mixing quality and a significant deterioration of the mechanical and thermal properties of the composites. Optimised mixing and extrusion parameters can be the starting point for the design of efficient twin-screw extruder plasticizing system for fabrication of PLA composites with carbon nanotube and graphene fillers