Anion induced displacement studies in naphthalene diimide containing interpenetrated and interlocked structures

This article describes investigations into the development of supramolecular systems capable of sensing anions through either displacement type assays or molecular motion. An electron deficient naphthalene diimide thread and electron rich isophthalamide naphthohydroquinone macrocycle was shown to form a coloured pseudorotaxane assembly. Investigations into the ability of such interpenetrated systems to sense anions colorimetrically were undertaken. Anion complexation to the isophthalamide group of the macrocycle causes displacement of the naphthodiimide thread resulting in the loss of colour. The enhanced mechanically bonded binding strength between the naphthodiimide axle and the naphthohydroquinone groups of the macrocycle wheel in the corresponding rotaxane structure however, was found to negate the anion induced displacement process.

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence

Abstract Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor endocytosis both in vitro, and in vivo. Receptor endocytosis serves at least two important functions in signal transduction. First, desensitization and endocytosis act as an "off" switch by uncoupling receptors from G protein. Second, endocytosis functions as an "on" switch, resensitizing receptors by recycling them to the plasma membrane. Thus, both the off and on function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether the low degree of endocytosis induced by morphine contributes to tolerance and dependence, we generated a knockin mouse that expresses a mutant MOP-R that undergoes morphine-induced endocytosis. Morphine remains an excellent antinociceptive agent in these mice. Importantly, these mice display substantially reduced antinociceptive tolerance and physical dependence. These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

Coherent superposition of exciton states in quantum dots induced by surface plasmons

We present an experimental demonstration of strong optical coupling between CdSequantum dots of different sizes which is induced by a surface plasmon propagating on a planar silver thin film. Attenuated total reflection measurements demonstrate the hybridization of exciton states, characterized by the observation of two avoided crossings in the energy dispersion measured for the interacting system.

Characterizing the signal pattern of a four-cylinder diesel engine using acoustic emission and vibration analysis

Condition monitoring of diesel engines can prevent unpredicted engine failures and the associated consequence. This paper presents an experimental study of the signal characteristics of a 4-cylinder diesel engine under various loading conditions. Acoustic emission, vibration and in-cylinder pressure signals were employed to study the effectiveness of these techniques for condition monitoring and identifying symptoms of incipient failures. An event driven synchronous averaging technique was employed to average the quasi-periodic diesel engine signal in the time domain to eliminate or minimize the effect of engine speed and amplitude variations on the analysis of condition monitoring signal. It was shown that acoustic emission (AE) is a better technique than vibration method for condition monitor of diesel engines due to its ability to produce high quality signals (i.e., excellent signal to noise ratio) in a noisy diesel engine environment. It was found that the peak amplitude of AE RMS signals correlating to the impact-like combustion related events decreases in general due to a more stable mechanical process of the engine as the loading increases. A small shift in the exhaust valve closing time was observed as the engine load increases which indicates a prolong combustion process in the cylinder (to produce more power). On the contrary, peak amplitudes of the AE RMS attributing to fuel injection increase as the loading increases. This can be explained by the increase fuel friction caused by the increase volume flow rate during the injection. Multiple AE pulses during the combustion process were identified in the study, which were generated by the piston rocking motion and the interaction between the piston and the cylinder wall. The piston rocking motion is caused by the non-uniform pressure distribution acting on the piston head as a result of the non-linear combustion process of the engine. The rocking motion ceased when the pressure in the cylinder chamber stabilized.

Quantifying in-plane deformation of plate elements using vibration characteristics

Plate elements are used in many engineering applications. In-plane loads and deformations have significant influence on the vibration characteristics of plate elements. Numerous methods have been developed to quantify the effects of in-plane loads and deformations of individual plate elements with different boundary conditions based on their natural frequencies. However, these developments cannot be applied to the plate elements in a structural system as the natural frequency is a global parameter for the entire structure. This highlights the need for a method to quantify in-plane deformations of plate elements in structural framing systems. Motivated by this gap in knowledge, this research has developed a comprehensive vibration based procedure to quantify in-plane deformation of plate elements in a structural framing system. This procedure with its unique capabilities to capture the influence of load migration, boundary conditions and different tributary areas is presented herein and illustrated through examples.

Experimentally induced diesel engine injector faults and some preliminary acoustic emission signal observations

Diesel engine fuel injector faults can lead to reduced power, increased fuel consumption and greater exhaust emission levels and if left unchecked, can eventually lead to premature engine failure. This paper provides an overview of the Diesel, or compression ignition combustion process, and of the two basic fuel injector nozzle designs used in Diesel engines, namely, the pintle-type and hole-type nozzles. Also described are some common faults associated with these two types of fuel injector nozzles and the techniques previously used to experimentally simulate these faults. This paper also presents a recent experimental campaign undertaken using two different diesel engines whereby various fuel injector nozzle faults were induced into the engines. The first series of tests was undertaken using a turbo-charged 5.9 litre; Cummins Diesel engine whist the second series of tests was undertaken using a naturally aspirated 4 cylinder, 2.216 litre, Perkins Diesel engine. Data corresponding to different injector fault conditions was captured using in-cylinder pressure, and acoustic emission transducers along with both crank-angle encoder and top-dead centre reference signals. Using averaged in-cylinder pressure signals, it was possible to qualify the severity of the faults whilst averaged acoustic emission signals were in turn, used as the basis for wavelets decomposition. Initial observations from this signal decomposition are also presented and discussed.

Substance-induced psychosis : a diagnostic conundrum

Objective: To critically examine the DSM-IV-TR criteria for Substance-Induced Psychotic Disorder (SIPD). Data sources: Leading electronic databases (such as Medline, Pubmed) were searched for the years 1992 through 2007, using combinations of the following key search terms: substance abuse/dependence, alcohol, marijuana, cannabis, methamphetamine, crack, cocaine, amphetamine, ecstasy, ketamine, phencyclidine, LSD, mental health, drug-induced psychosis, substance-induced psychosis, psychosis, schizophrenia. References identified from bibliographies of pertinent articles and books in the field were also collected and reviewed. Data extraction: Only research studies or case reports series that presented data on populations diagnosed with SIPD using clinical or structured diagnostic interviews published in English were used to assess the validity of the current SIPD criteria. Data synthesis: We identified 49 articles that presented clinical data on SIPD. The majority of these publications were case reports, with only 18 articles specifically focusing on delineating the clinical characteristics or outcomes of individuals diagnosed with SIPD. While several large studies have recently been conducted to assess the stability of SIPD, there is a dearth of research rigorously examining the validity of DSM-IV diagnostic criteria across substances. Conclusions: There remains a striking paucity of information on the outcome, treatment and best practice for substance-associated psychotic episodes. Further work is clearly required before the advent of DSM-V. We propose an alternative, broader classification that better reflects the current evidence base, inferring association rather than causation.

An analytical and experimental study of the vibration response of a clamped ribbed plate

An analytical solution is presented in this paper for the vibration response of a ribbed plate clamped on all its boundary edges by employing a travelling wave solution. A clamped ribbed plate test rig is also assembled in this study for the experimental investigation of the ribbed plate response and to provide verification results to the analytical solution. The dynamic characteristics and mode shapes of the ribbed plate are measured and compared to those obtained from the analytical solution and from finite element analysis (FEA). General good agreements are found between the results. Discrepancies between the computational and experimental results at low and high frequencies are also discussed. Explanations are offered in the study to disclose the mechanism causing the discrepancies. The dependency of the dynamic response of the ribbed plate on the distance between the excitation force and the rib is also investigated experimentally. It confirms the findings disclosed in a previous analytical study [T. R. Lin and J. Pan, A closed form solution for the dynamic response of finite ribbed plates. Journal of the Acoustical Society of America 119 (2006) 917-925] that the vibration response of a clamped ribbed plate due to a point force excitation is controlled by the plate stiffness when the source is more than a quarter plate bending wavelength away from the rib and from the plate boundary. The response is largely affected by the rib stiffness when the source location is less than a quarter bending wavelength away from the rib.