Disruption of nNOS-NOS1AP protein-protein interactions suppresses neuropathic pain in mice

Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central sensitization and chronic pain. However, NMDAR antagonists display limited therapeutic potential because of their adverse side effects. Novel approaches targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of NMDARs show efficacy in preclinical pain models. Here, we evaluated the involvement of interactions between neuronal nitric oxide synthase (nNOS) and the nitric oxide synthase 1 adaptor protein (NOS1AP) in pronociceptive signaling and neuropathic pain. TAT-GESV, a peptide inhibitor of the nNOS-NOS1AP complex, disrupted the in vitro binding between nNOS and its downstream protein partner NOS1AP but not its upstream protein partner postsynaptic density 95 kDa (PSD95). Putative inactive peptides (TAT-cp4GESV and TAT-GESVΔ1) failed to do so. Only the active peptide protected primary cortical neurons from glutamate/glycine-induced excitotoxicity. TAT-GESV, administered intrathecally (i.t.), suppressed mechanical and cold allodynia induced by either the chemotherapeutic agent paclitaxel or a traumatic nerve injury induced by partial sciatic nerve ligation. TAT-GESV also blocked the paclitaxel-induced phosphorylation at Ser15 of p53, a substrate of p38 MAPK. Finally, TAT-GESV (i.t.) did not induce NMDAR-mediated motor ataxia in the rotarod test and did not alter basal nociceptive thresholds in the radiant heat tail-flick test. These observations support the hypothesis that antiallodynic efficacy of an nNOS-NOS1AP disruptor may result, at least in part, from blockade of p38 MAPK-mediated downstream effects. Our studies demonstrate, for the first time, that disrupting nNOS-NOS1AP protein-protein interactions attenuates mechanistically distinct forms of neuropathic pain without unwanted motor ataxic effects of NMDAR antagonists

Effect of hot water pretreatment severity on the degradation and enzymatic hydrolysis of corn stover

The effects of hot water pretreatment on the degradation and enzymatic hydrolysis of corn stover were studied. Nearly 100% cellulose recovery in the solid fraction was obtained when corn stover was pretreated at 170 degrees C to 210 degrees C for 3 to 10 min. The highest pretreatment severity of 4.239 (210 degrees C, 10 min) resulted in the highest solid solubilization (37.0%) and xylan solubilization (90.5%). At this severity, inhibitors such as acetic acid, furfural, and hydroxymethyl furfural (HMF) also reached the highest levels of 7.1, 4.6, and 0.6 g L-1, respectively. When the pretreatment temperature was less than 190 degrees C, the furfural concentration was below 1.0 g L-1 and no significant levels of HMF were detected. Enzymatic hydrolysis results showed that increased glucose yields were obtained with increased pretreatment temperatures of corn stover The highest glucose yield of 89.2% was obtained at the pretreatment severity of 3.716 (210 degrees C, 3 min). Due to the degradation of sugars, a glucose yield of 85.9% was obtained at the highest pretreatment severity of 4.239 (210 degrees C, 10 min)

Classification of Overlapped Audio Events Based on AT, PLSA, and the Combination of Them

Audio event classification, as an important part of Computational Auditory Scene Analysis, has attracted much attention. Currently, the classification technology is mature enough to classify isolated audio events accurately, but for overlapped audio events, it performs much worse. While in real life, most audio documents would have certain percentage of overlaps, and so the overlap classification problem is an important part of audio classification. Nowadays, the work on overlapped audio event classification is still scarce, and most existing overlap classification systems can only recognize one audio event for an overlap. In this paper, in order to deal with overlaps, we innovatively introduce the author-topic (AT) model which was first proposed for text analysis into audio classification, and innovatively combine it with PLSA (Probabilistic Latent Semantic Analysis). We propose 4 systems, i.e. AT, PLSA, AT-PLSA and PLSA-AT, to classify overlaps. The 4 proposed systems have the ability to recognize two or more audio events for an overlap. The experimental results show that the 4 systems perform well in classifying overlapped audio events, whether it is the overlap in training set or the overlap out of training set. Also they perform well in classifying isolated audio events

A new class of efficient piecewise nonlinear chaotic maps for secure cryptosystems

In this paper we construct a new class of nonlinear chaotic maps for secure cryptosystems. These maps can overcome the security holes brought by the "piecewise linearity" of the previous Piecewise Linear Chaotic Maps (PWLCM) due to a fact that the chaotic sequences generated by the derived iterative system based on the proposed maps are proved to have perfect dynamic properties, such as uniform invariant distribution, d-like autocorrelation function etc. Furthermore, the relative quantized two-value sequences also have perfect secure statistical characteristics. In terms of computing speed, the proposed maps have faster speed than the recently proposed nonlinear "piecewise-square-root" maps (PSRM), and they actually have equivalently the same computing speed with the linear PWLCM

Retrieval of phase memory in two independent atomic ensembles by Raman process

In spontaneous Raman process in atomic cell at high gain, both the Stokes field and the accompanying collective atomic excitation (atomic spin wave) are coherent. We find that, due to the spontaneous nature of the process, the phases of the Stokes field and the atomic spin wave change randomly from one realization to another but are anti-correlated. The phases of the atomic ensembles are read out via another Raman process at a later time, thus realizing phase memory in atoms. The observation of phase correlation between the Stokes field and the collective atomic excitations is an important step towards macroscopic EPR-type entanglement of continuous variables between light and atoms

T1ρ-based fibril-reinforced poroviscoelastic constitutive relation of human articular cartilage using inverse finite element technology

BackgroundMapping of T1ρ relaxation time is a quantitative magnetic resonance (MR) method and is frequently used for analyzing microstructural and compositional changes in cartilage tissues. However, there is still a lack of study investigating the link between T1ρ relaxation time and a feasible constitutive relation of cartilage which can be used to model complicated mechanical behaviors of cartilage accurately and properly.MethodsThree-dimensional finite element (FE) models of ten in vitro human tibial cartilage samples were reconstructed such that each element was assigned by material-level parameters, which were determined by a corresponding T1ρ value from MR maps. A T1ρ-based fibril-reinforced poroviscoelastic (FRPE) constitutive relation for human cartilage was developed through an inverse FE optimization technique between the experimental and simulated indentations.ResultsA two-parameter exponential relationship was obtained between the T1ρ and the volume fraction of the hydrated solid matrix in the T1ρ-based FRPE constitutive relation. Compared with the common FRPE constitutive relation (i.e., without T1ρ), the T1ρ-based FRPE constitutive relation indicated similar indentation depth results but revealed some different local changes of the stress distribution in cartilages.ConclusionsOur results suggested that the T1ρ-based FRPE constitutive relation may improve the detection of changes in the heterogeneous, anisotropic, and nonlinear mechanical properties of human cartilage tissues associated with joint pathologies such as osteoarthritis (OA). Incorporating T1ρ relaxation time will provide a more precise assessment of human cartilage based on the individual in vivo MR quantification

Orthogonal decomposition of core loss along rolling and transverse directions of non-grain oriented silicon steels

© 2017 Author(s). Rotational core loss of the silicon steel laminations are measured under elliptical rotating excitation. The core loss decomposition model is very important in magnetic core design, in which the decomposition coefficients are calculated through the measurement data. By using the transformation of trigonometric function, the elliptical rotational magnetic flux can be decomposed into two parts along two directions. It is assumed that the rotating core loss is the sum of alternating core losses along rolling and transverse directions. The magnetic strength vector H of non-grain oriented (NGO) silicon steel 35WW270 along rolling and transverse directions is measured by a novel designed 3-D magnetic properties tester. Alternating core loss along the rolling, transverse directions and rotating core loss in the xoy-plane of this specimen in different frequencies such as 50 Hz, 100 Hz, and 200 Hz. Experimental results show that the core loss model is more accurate and useful to predict the total core loss