Solving Gravity Anomaly Matching Problem Under Large Initial Errors in Gravity Aided Navigation by Using an Affine Transformation Based Artificial Bee Colony Algorithm.

Gravity aided inertial navigation system (GAINS), which uses earth gravitational anomaly field for navigation, holds strong potential as an underwater navigation system. The gravity matching algorithm is one of the key factors in GAINS. Existing matching algorithms cannot guarantee the matching accuracy in the matching algorithms based gravity aided navigation when the initial errors are large. Evolutionary algorithms, which are mostly have the ability of global optimality and fast convergence, can be used to solve the gravity matching problem under large initial errors. However, simply applying evolutionary algorithms to GAINS may lead to false matching. Therefore, in order to deal with the underwater gravity matching problem, it is necessary to improve the traditional evolutionary algorithms. In this paper, an affine transformation based artificial bee colony (ABC) algorithm, which can greatly improve the positioning precision under large initial errors condition, is developed. The proposed algorithm introduces affine transformation to both initialization process and evolutionary process of ABC algorithm. The single-point matching strategy is replaced by the strategy of matching a sequence of several consecutive position vectors. In addition, several constraints are introduced to the process of evolution by using the output characteristics of the inertial navigation system (INS). Simulations based on the actual gravity anomaly base map have been performed for the validation of the proposed algorithm.

Tracking Architecture Based on Dual-Filter with State Feedback and Its Application in Ultra-Tight GPS/INS Integration.

If a Kalman Filter (KF) is applied to Global Positioning System (GPS) baseband signal preprocessing, the estimates of signal phase and frequency can have low variance, even in highly dynamic situations. This paper presents a novel preprocessing scheme based on a dual-filter structure. Compared with the traditional model utilizing a single KF, this structure avoids carrier tracking being subjected to code tracking errors. Meanwhile, as the loop filters are completely removed, state feedback values are adopted to generate local carrier and code. Although local carrier frequency has a wide fluctuation, the accuracy of Doppler shift estimation is improved. In the ultra-tight GPS/Inertial Navigation System (INS) integration, the carrier frequency derived from the external navigation information is not viewed as the local carrier frequency directly. That facilitates retaining the design principle of state feedback. However, under harsh conditions, the GPS outputs may still bear large errors which can destroy the estimation of INS errors. Thus, an innovative integrated navigation filter is constructed by modeling the non-negligible errors in the estimated Doppler shifts, to ensure INS is properly calibrated. Finally, field test and semi-physical simulation based on telemetered missile trajectory validate the effectiveness of methods proposed in this paper.

Spinal SIRT1 activation attenuates neuropathic pain in mice.

Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1), a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD) in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI) or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

Chronic treatment with anesthetic propofol attenuates ß-amyloid protein levels in brain tissues of aged mice.

Alzheimer's disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of ß-amyloid protein (Aß) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aß levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aß (Aß40 and Aß42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of ß-site amyloid precursor protein cleaving enzyme (the enzyme for Aß generation), and increased the levels of neprilysin (the enzyme for Aß degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aß levels potentially via decreasing brain levels of ß-site amyloid precursor protein cleaving enzyme, thus decreasing Aß generation; and via increasing brain neprilysin levels, thus increasing Aß degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research.

Chronic treatment with anesthetic propofol improves cognitive function and attenuates caspase activation in both aged and Alzheimer's disease transgenic mice.

There is a need to seek new treatment(s) for Alzheimer's disease (AD). A recent study showed that AD patients may have decreased levels of functional GABA receptors. Propofol, a commonly used anesthetic, is a GABA receptor agonist. We therefore set out to perform a proof of concept study to determine whether chronic treatment with propofol (50 mg/kg/week) can improve cognitive function in both aged wild-type (WT) and AD transgenic (Tg) mice. Propofol was administrated to the WT and AD Tg mice once a week for 8 or 12 weeks, respectively. Morris water maze was used to assess the cognitive function of the mice following the propofol treatment. Activation of caspase-3, caspase-9, and caspase-8 was investigated using western blot analysis at the end of the propofol treatment. In the mechanistic studies, effects of propofol, amyloid-ß protein (Aß), and GABA receptor antagonist flumazenil on caspase-3 activation and opening of the mitochondrial permeability transition pore were assessed in H4 human neuroglioma and mouse neuroblastoma cells by western blot analysis and flow cytometry. Here we showed that the propofol treatment improved cognitive function and attenuated brain caspase-3 and caspase-9 activation in both aged WT and AD Tg mice. Propofol attenuated Aß-induced caspase-3 activation and opening of the mitochondrial permeability transition pore in the cells, and flumazenil inhibited the propofol's effects. These results suggested that propofol might improve cognitive function via attenuating the Aß-induced mitochondria dysfunction and caspase activation, which explored the potential that anesthetic propofol could improve cognitive function in elderly and AD patients.

ERK MAP kinase activation in spinal cord regulates phosphorylation of Cdk5 at serine 159 and contributes to peripheral inflammation induced pain/hypersensitivity.

Cyclin-dependent kinase 5 is a proline-directed serine/threonine kinase and its activity participates in the regulation of nociceptive signaling. Like binding with the activators (P35 or P25), the phosphorylation of Cdk5 plays a critical role in Cdk5 activation. However, it is still unclear whether Cdk5 phosphorylation (p-Cdk5) contributes to pain hyperalgesia. The aim of our current study was to identify the roles of p-Cdk5 and its upstream regulator in response to peripheral inflammation. Complete Freund's adjuvant (CFA) injection induced acute peripheral inflammation and heat hyperalgesia, which was accompanied by sustained increases in phospho-ERK1/2 (p-ERK1/2) and phospho-Cdk5(S159) (p-Cdk5(S159)) in the spinal cord dorsal horn (SCDH). CFA-induced p-ERK primarily colocalized with p-Cdk5(S159) in superficial dorsal horn neurons. Levels in p-ERK and p-Cdk5 were also increased in the 2(nd) phase of hyperalgesia induced by formalin injection, which can produce acute and tonic inflammatory pain. MAP kinase kinase inhibitor U0126 intrathecal delivery significantly suppressed the elevation of p-Cdk5(S159), Cdk5 activity and pain response behavior (Heat hyperalgesia, Spontaneous flinches) induced by CFA or formalin injection. Cdk5 inhibitor roscovitine intrathecal administration also suppressed CFA-induced heat hyperalgesia and Cdk5 phosphorylation, but did not attenuate ERK activation. All these findings suggested that p-Cdk5(S159) regulated by ERK pathway activity may be a critical mechanism involved in the activation of Cdk5 in nociceptive spinal neurons contributes to peripheral inflammatory pain hypersensitivity.

The BDNF/TrkB signaling pathway is involved in heat hyperalgesia mediated by Cdk5 in rats.

BACKGROUND: Cyclin-dependent kinase 5 (Cdk5) has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) via the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway in the dorsal horn of the spinal cord in rats. RESULTS: Heat hyperalgesia induced by peripheral injection of CFA was significantly reversed by roscovitine, TrkB-IgG, and the TrkB inhibitor K252a, respectively. Furthermore, BDNF was significantly increased from 0.5 h to 24 h after CFA injection in the spinal cord dorsal horn. Intrathecal adminstration of the Cdk5 inhibitor roscovitine had no obvious effects on BDNF levels. Increased TrkB protein level was significantly reversed by roscovitine between 0.5 h and 6 h after CFA injection. Cdk5 and TrkB co-immunoprecipitation results suggested Cdk5 mediates the heat hyperalgesia induced by CFA injection by binding with TrkB, and the binding between Cdk5 and TrkB was markedly blocked by intrathecal adminstration of roscovitine. CONCLUSION: Our data suggested that the BDNF-TrkB signaling pathway was involved in CFA-induced heat hyperalgesia mediated by Cdk5. Roscovitine reversed the heat hyperalgesia induced by peripheral injection of CFA by blocking BDNF/TrkB signaling pathway, suggesting that severing the close crosstalk between Cdk5 and the BDNF/TrkB signaling cascade may present a potential target for anti-inflammatory pain.

Effect of thoracic epidural anesthesia with different concentrations of ropivacaine on arterial oxygenation during one-lung ventilation.

BACKGROUND: Thoracic epidural anesthesia can contribute to facilitate the fast-track approach in lung surgery. However, data regarding the effects of thoracic epidural anesthesia on oxygenation during one-lung ventilation (OLV) are scarce and contradictory. Therefore, the authors conducted a prospective, randomized, double-blinded trial in patients undergoing lung surgery under spectral entropy-guided intravenous anesthesia to evaluate the effects of thoracic epidural anesthesia with different concentrations of ropivacaine on oxygenation, shunt fraction (Qs/Qt) during OLV, and maintenance doses of propofol. METHODS: One hundred twenty patients scheduled for lung surgery were randomly divided into four groups to epidurally receive saline (Group S), 0.25% (Group R0.25), 0.50% (Group R0.50), and 0.75% (Group R0.75) ropivacaine. Ropivacaine was administered intraoperatively (6-8 ml of first bolus + 5 ml/h infusion). Arterial oxygen tension (Pao2) and Qs/Qt were measured before, during, and after OLV. RESULTS: Pao2 was significantly lower in Group R0.75 compared with that in Group S and Group R0.25 10 min (170 +/- 61 vs. 229 +/- 68 mmHg, P = 0.01; 170 +/- 61 vs. 223 +/- 70 mmHg, P = 0.03) and 20 min after OLV (146 +/- 52 vs. 199 +/- 68 mmHg, P = 0.009; 146 +/- 52 vs. 192 +/- 67 mmHg, P = 0.03). During OLV, Qs/Qt was significantly higher in Group R0.75 compared with that in Group S and Group R0.25 (P < 0.05). Maintenance doses of propofol were significantly lower in Group R0.75. Vasopressor requirements were higher in Group R0.75. CONCLUSION: A decrease in oxygenation during OLV occurred only at the highest dose of epidural local anesthetic and not at lower doses. Higher doses of epidural medication required less propofol and more vasopressors.