Apaf-1 Inhibitors Protect from Unwanted Cell Death in In Vivo Models of Kidney Ischemia and Chemotherapy Induced Ototoxicity

Background: Excessive apoptosis induces unwanted cell death and promotes pathological conditions. Drug discovery efforts aimed at decreasing apoptotic damage initially targeted the inhibition of effector caspases. Although such inhibitors were effective, safety problems led to slow pharmacological development. Therefore, apoptosis inhibition is still considered an unmet medical need. Methodology and Principal Findings: The interaction between Apaf-1 and the inhibitors was confirmed by NMR. Target specificity was evaluated in cellular models by siRNa based approaches. Cell recovery was confirmed by MTT, clonogenicity and flow cytometry assays. The efficiency of the compounds as antiapoptotic agents was tested in cellular and in vivo models of protection upon cisplatin induced ototoxicity in a zebrafish model and from hypoxia and reperfusion kidney damage in a rat model of hot ischemia. Conclusions: Apaf-1 inhibitors decreased Cytc release and apoptosome-mediated activation of procaspase-9 preventing cell and tissue damage in ex vivo experiments and in vivo animal models of apoptotic damage. Our results provide evidence that Apaf-1 pharmacological inhibition has therapeutic potential for the treatment of apoptosis-related diseases.

Usage of substances and their dosage regimes in pharmacological animal models of schizophrenia

Background: Contrary to what is generally thought schizophrenia is a very common mental health issue. For this, several animal models are used to assess the illness in order to develop a definitive. The most widely spread paradigm is the use of pharmacological models. Aim: The aim of this review is to display which are the most used insults for the assessment of social behaviour related negative symptoms in animal models as well as to ascertain which is the most adequate regime. Design: Literature review. Methods: PubMed database was used for this article by the search of the indexed “schizophrenia”, “animal models”, “social behaviour” and “negative symptoms” descriptors. With the exception of a single article due to it value this review is based on articles from 10 years onwards. Besides, only clinical trials and reviews written in English or Spanish and that had laboratory rodents as target population were accepted. Results: The studies assessed agree that pharmacological models (specially those regarding the NMDA receptor antagonists) are a valuable means for the experimental investigation of negative symptoms in schizophrenia with the necessity to emphasise that only some negative symptoms (anhedonia and social interaction, mainly) can be experimentally assessed. Conclusions: There is not enough evidence regarding the fours aspects of this review. PCP, Ketamine or MK-801 in sub-acute dosage regimes are currently the most indicated insults to mimic schizophrenic symptoms in rodents, although further research in needed, albeit other substances are valuable as well. (In English language exclusively)

Prediction and suppression of strong dispersive coupling in microracetrack channel drop filters

For a four-port microracetrack channel drop filter, unexpected transmission characteristics due to strong dispersive coupling are demonstrated by the light tunneling between the input-output waveguides and the resonator, where a large dropping transmission at off-resonance wavelengths is observed by finite-difference time-domain simulation. It causes a severe decline of the extinction ratio and finesse. An appropriate decrease of the coupling strength is found to suppress the dispersive coupling and greately increase the extinction ratio and finesse, a decreased coupling strength can be realized by the application of an asymmetrical coupling waveguide structure. In addition, the profile of the coupling dispersion in the transmission spectra can be predicted based on a coupled mode theory analysis of an equivalent system consisting of two coupling straight waveguides. The effects of structure parameters on the transmission spectra obtained by this method agree well with the numerical results. It is useful to avoid the strong dispersive coupling region in the filter design. (c) 2007 Optical Society of America.

Discussion on the basic mathematical models of neurons - Double synaptic weight neuron in general-purpose neurocomputer, theory and application

Based on the introduction of the traditional mathematical models of neurons in general-purpose neurocomputer, a novel all-purpose mathematical model-Double synaptic weight neuron (DSWN) is presented, which can simulate all kinds of neuron architectures, including Radial-Basis-Function (RBF) and Back-propagation (BP) models, etc. At the same time, this new model is realized using hardware and implemented in the new CASSANN-II neurocomputer that can be used to form various types of neural networks with multiple mathematical models of neurons. In this paper, the flexibility of the new model has also been described in constructing neural networks and based on the theory of Biomimetic pattern recognition (BPR) and high-dimensional space covering, a recognition system of omni directionally oriented rigid objects on the horizontal surface and a face recognition system had been implemented on CASSANN-H neurocomputer. The result showed DSWN neural network has great potential in pattern recognition.

A unified criterion for initiation of sediment motion and inception of sheet flow under water waves

A unified criterion is developed for initiation of non-cohesive sediment motion and inception of sheet flow under water waves over a horizontal bed of sediment based on presently available experimental data. The unified threshold criterion is of the single form, U-o = 2 pi C[1 + 5(T-R/T)(2)](-1/4), where U-o is the onset velocity of sediment motion or sheet flow, T is wave period, and C and T-R are the coefficients. It is found that for a given sediment, U-o initially increases sharply with wave period, then gradually approaches the maximum onset velocity U-o = 2 pi C and becomes independent of T when T is larger. The unified criterion can also be extended to define sediment initial motion and sheet flow under irregular waves provided the significant wave orbital velocity and period of irregular waves are introduced in this unified criterion.

Models of Noise and Robust Estimates

Given n noisy observations g; of the same quantity f, it is common use to give an estimate of f by minimizing the function Eni=1(gi-f)2. From a statistical point of view this corresponds to computing the Maximum likelihood estimate, under the assumption of Gaussian noise. However, it is well known that this choice leads to results that are very sensitive to the presence of outliers in the data. For this reason it has been proposed to minimize the functions of the form Eni=1V(gi-f), where V is a function that increases less rapidly than the square. Several choices for V have been proposed and successfully used to obtain "robust" estimates. In this paper we show that, for a class of functions V, using these robust estimators corresponds to assuming that data are corrupted by Gaussian noise whose variance fluctuates according to some given probability distribution, that uniquely determines the shape of V.