The reactivity of organosilylamines of imidazole, pyrazole, 1,2,4-triazole and benzotriazole towards alkyl halides, acidic chlorides and halogenated ketones has been studied. Except for 1-trimethylsilylimidazole, which gives a mixed quaternary salt, reactions with primary halides lead to the corresponding 1-alkylated heterocyclic compounds in high yields; in each case only one isomer is obtained (1-alkyl-1,2,4-triazole and 1-alkylbenzotriazole). Similarly acidic chlorides give 1-acylated derivatives in quantitative yields. Finally α- or β-halogenated ketones show different behaviour and give the addition or substitution products. 相似文献
The differential diagnosis of epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) may be difficult, due to the lack of distinctive clinical features. The interictal electroencephalographic (EEG) signal may also be normal in patients with ES. Innovative diagnostic tools that exploit non-linear EEG analysis and deep learning (DL) could provide important support to physicians for clinical diagnosis. In this work, 18 patients with new-onset ES (12 males, 6 females) and 18 patients with video-recorded PNES (2 males, 16 females) with normal interictal EEG at visual inspection were enrolled. None of them was taking psychotropic drugs. A convolutional neural network (CNN) scheme using DL classification was designed to classify the two categories of subjects (ES vs. PNES). The proposed architecture performs an EEG time-frequency transformation and a classification step with a CNN. The CNN was able to classify the EEG recordings of subjects with ES vs. subjects with PNES with 94.4% accuracy. CNN provided high performance in the assigned binary classification when compared to standard learning algorithms (multi-layer perceptron, support vector machine, linear discriminant analysis and quadratic discriminant analysis). In order to interpret how the CNN achieved this performance, information theoretical analysis was carried out. Specifically, the permutation entropy (PE) of the feature maps was evaluated and compared in the two classes. The achieved results, although preliminary, encourage the use of these innovative techniques to support neurologists in early diagnoses. 相似文献
Uniformly sized microparticles of poly(d,l-lactic-co-glycolic) (PLGA) acid, with controllable median diameters within the size range 40–140 μm, were successfully prepared by membrane emulsification of an oil phase injected into an aqueous phase, followed by solvent removal. Initially, simple particles were produced as an oil in water emulsion, where dichloromethane (DCM) and PLGA were the oil phase and water with stabiliser was the continuous phase. The oil was injected into the aqueous phase through an array type microporous membrane, which has very regular pores equally spaced apart, and two different pore sizes were used: 20 and 40 μm in diameter. Shear was provided at the membrane surface, causing the drops to detach, by a simple paddle stirrer rotating above the membrane. Further tests involved the production of a primary water in oil emulsion, using a mechanical homogeniser, which was then subsequently injected into a water phase through the microporous membrane to form a water in oil in water emulsion. These tests used a water-soluble model drug (blue dextran) and encapsulation efficiencies of up to 100% were obtained for concentrations of 15% PLGA dissolved in the DCM and injected through a 40 μm membrane.
Solidification of the PLGA particles was followed by removal of the DCM through the surrounding aqueous continuous phase. Different PLGA concentrations, particle size and osmotic pressures were considered in order to find their effect on encapsulation efficiency. Osmotic pressure was varied by changing the salt concentration in the external aqueous phase whilst maintaining a constant internal aqueous phase salt concentration. Osmotic pressure was found to be a significant factor on the resulting particle structure, for the tests conducted at lower PLGA concentrations (10% and 5% PLGA). The PLGA concentration and particle size distribution influence the time to complete the solidification stage and a slow solidification, formed by stirring gently overnight, provided the most monosized particles and highest encapsulation efficiency. 相似文献
Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.
Results
To investigate the role of parkin, we have generated transgenic Drosophila that conditionally express parkin under the control of the yeast UAS enhancer. While expression of parkin has little consequence, co-expression of parkin with α-synuclein in the dopaminergic neurons suppresses the α-synuclein-induced premature loss of climbing ability. In addition directed expression of parkin in the eye counteracts the α-synuclein-induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α-synuclein-dependent Drosophila model of PD.
Conclusion
The highly conserved parkin E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of parkin should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.
We report measurements of the superfluid fraction rho(s)/rho of films of (3)He-(4)He mixtures confined between silicon wafers at 0.0483 microm separation. The data obtained using adiabatic fountain resonance (AFR) can be used to test for the first time expectations of correlation-length scaling in the case of planar mixtures. For the mixtures, the data for rho(s)/rho collapse well on a universal function. The dissipation associated with AFR can also be scaled, and indicates two-dimensional crossover. These results are in contrast to pure (4)He, where over a wider range of confinements, the data for rho(s)/rho are found not to scale. 相似文献
The phase behavior of rod-plate mixtures was investigated using model systems containing unambiguously rod- and plate-shaped colloids. We find that the theoretically disputed biaxial nematic phase is unstable with respect to demixing into an isotropic and two uniaxial nematic phases. The phase behavior at very high densities is exceptionally rich and includes the coexistence of up to four different liquid crystalline phases, which stem from the coupling between the employed particle shapes and polydispersity. 相似文献