Thermo-Mechanical Characterization of Metal-Polymer Friction Stir Composite Joints-A Full Factorial Design of Experiments.

With the increasing demand for lighter, more environmentally friendly, and affordable solutions in the mobility sector, designers and engineers are actively promoting the use of innovative integral dissimilar structures. In this field, friction stir-based technologies offer unique advantages compared with conventional joining technologies, such as mechanical fastening and adhesive bonding, which recently demonstrated promising results. In this study, an aluminum alloy and a glass fiber-reinforced polymer were friction stir joined in an overlap configuration. To assess the main effects, interactions, and influence of processing parameters on the mechanical strength and processing temperature of the fabricated joints, a full factorial design study with three factors and two levels was carried out. The design of experiments resulted in statistical models with excellent fit to the experimental data, enabling a thorough understanding of the influence of rotational speed, travel speed, and tool tilt angle on dissimilar metal-to-polymer friction stir composite joints. The mechanical strength of the composite joints ranged from 1708.1 ± 45.5 N to 3414.2 ± 317.1, while the processing temperature was between 203.6 ± 10.7 °C and 251.5 ± 9.7.

Oxidative stress induced by sustained supraphysiological intrastriatal GDNF delivery is prevented by dose regulation.

Despite its established neuroprotective effect on dopaminergic neurons and encouraging phase I results, intraputaminal GDNF administration failed to demonstrate significant clinical benefits in Parkinson's disease patients. Different human GDNF doses were delivered in the striatum of rats with a progressive 6-hydroxydopamine lesion using a sensitive doxycycline-regulated AAV vector. GDNF treatment was applied either continuously or intermittently (2 weeks on/2 weeks off) during 17 weeks. Stable reduction of motor impairments as well as increased number of dopaminergic neurons and striatal innervation were obtained with a GDNF dose equivalent to 3- and 10-fold the rat endogenous level. In contrast, a 20-fold increased GDNF level only temporarily provided motor benefits and neurons were not spared. Strikingly, oxidized DNA in the substantia nigra increased by 50% with 20-fold, but not 3-fold GDNF treatment. In addition, only low-dose GDNF allowed to preserve dopaminergic neuron cell size. Finally, aberrant dopaminergic fiber sprouting was observed with 20-fold GDNF but not at lower doses. Intermittent 20-fold GDNF treatment allowed to avoid toxicity and spare dopaminergic neurons but did not restore their cell size. Our data suggest that maintaining GDNF concentration under a threshold generating oxidative stress is a pre-requisite to obtain significant symptomatic relief and neuroprotection.

Fluoride Exposure from Soybean Beverage Consumption: A Toxic Risk Assessment.

The consumption of vegetable milk as a substitute for cow's milk has increased in recent years. Of all the vegetable beverages on the market, soy is the most widely consumed. Soy is exposed to contamination by different chemical elements during harvesting. In this study, the concentration of fluoride in soy beverages was analyzed. Fluoride is an element that in high concentrations can be toxic, causing dental and bone fluorosis. The aims of the study were (i) to analyze the fluoride concentration in 30 samples in the most popular brands (A-Brand, B-Brand, C-Brand) of soybean beverages by a fluoride ion selective potentiometer and (ii) to evaluate the toxicological risk derived from its consumption. The fluoride concentrations were 15.5 mg/L (A-Brand), 11.3 mg/L (B-Brand) and 8.5 mg/L (C-Brand). A consumption of 1 to 3 servings/day was established. One serving (200 mL) of soybean beverage offered a contribution percentage over the ADI (acceptable daily intake) for infants and children. Teenagers and adults did not exceed the ADI (10 mg/day). The consumption of soy beverages contributes significantly to the daily intake of fluoride, which could exceed the ADI with a consequent health risk. It is recommended to control the fluoride levels in the raw material and in the final product to assure the safety of these products.

Prolonged dopamine D3 receptor stimulation promotes dopamine transporter ubiquitination and degradation through a PKC-dependent mechanism.

The dopamine transporter (DAT) is a membrane glycoprotein in dopaminergic neurons, which modulates extracellular and intracellular dopamine levels. DAT is regulated by different presynaptic proteins, including dopamine D2 (D2R) and D3 (D3R) receptors. While D2R signalling enhances DAT activity, some data suggest that D3R has a biphasic effect. However, despite the extensive therapeutic use of D2R/D3R agonists in neuropsychiatric disorders, this phenomenon has been little studied. In order to shed light on this issue, DAT activity, expression and posttranslational modifications were studied in mice and DAT-D3R-transfected HEK cells. Consistent with previous reports, acute treatment with D2R/D3R agonists promoted DAT recruitment to the plasma membrane and an increase in DA uptake. However, when the treatment was prolonged, DA uptake and total striatal DAT protein declined below basal levels. These effects were inhibited in mice by genetic and pharmacological inactivation of D3R, but not D2R, indicating that they are D3R-dependent. No changes were detected in mesostriatal tyrosine hydroxylase (TH) protein expression and midbrain TH and DAT mRNAs, suggesting that the dopaminergic system is intact and DAT is posttranslationally regulated. The use of immunoprecipitation and cell surface biotinylation revealed that DAT is phosphorylated at serine residues, ubiquitinated and released into late endosomes through a PKCß-dependent mechanism. In sum, the results indicate that long-term D3R activation promotes DAT down-regulation, an effect that may underlie neuroprotective and antidepressant actions described for some D2R/D3R agonists.

Local Response of Sialoliths to Lithotripsy: Cues on Fragmentation Outcome.

Lithotripsy methods show relatively low efficiency in the fragmentation of sialoliths compared with the success rates achieved in the destruction of renal calculi. However, the information available on the mechanical behavior of sialoliths is limited and their apparently tougher response is not fully understood. This work evaluates the hardness and Young's modulus of sialoliths at different scales and analyzes specific damage patterns induced in these calcified structures by ultrasonic vibrations, pneumoballistic impacts, shock waves, and laser ablation. A clear correlation between local mechanical properties and ultrastructure/chemistry has been established: sialoliths are composite materials consisting of hard and soft components of mineralized and organic nature, respectively. Ultrasonic and pneumoballistic reverberations damage preferentially highly mineralized regions, leaving relatively unaffected the surrounding organic matter. In contrast, shock waves leach the organic component and lead to erosion of the overall structure. Laser ablation destroys homogeneously the irradiated zones regardless of the mineralized/organic nature of the underlying ultrastructure; however, damage is less extensive than with mechanical methods. Overall, the present results show that composition and internal structure are key features behind sialoliths' comminution behavior and that the organic matter contributes to reduce the therapeutic efficiency of lithotripsy methods.