A comparison of the gas phase acidities of phospholipid headgroups: Experimental and computational studies

Proton-bound dimers consisting of two glycerophospholipids with different headgroups were prepared using negative ion electrospray ionization and dissociated in a triple quadrupole mass spectrometer. Analysis of the tandem mass spectra of the dimers using the kinetic method provides, for the first time, an order of acidity for the phospholipid classes in the gas phase of PE < PA << PG < PS < PI. Hybrid density functional calculations on model phospholipids were used to predict the absolute deprotonation enthalpies of the phospholipid classes from isodesmic proton transfer reactions with phosphoric acid. The computational data largely support the experimental acidity trend, with the exception of the relative acidity ranking of the two most acidic phospholipid species. Possible causes of the discrepancy between experiment and theory are discussed and the experimental trend is recommended. The sequence of gas phase acidities for the phospholipid headgroups is found to (1) have little correlation with the relative ionization efficiencies of the phospholipid classes observed in the negative ion electrospray process, and (2) correlate well with fragmentation trends observed upon collisional activation of phospholipid \[M - H](-) anions. (c) 2005 American Society for Mass Spectrometry.

Generation and characterization of ionic and neutral dihydroxy boron B(OH)(2)(+/0) in the gas phase

The dicoordinated borinium ion, dihydroxyborinium, B(OH)(2)(+) is generated from methyl boronic acid CH3B(OH)(2) by dissociative electron ionization and its connectivity confirmed by collisional activation. Neutralization-reionization (NR) experiments on this ion indicate that the neutral B(OH)(2) radical is a viable species in the gas phase. Both vertical neutralization of B(OH)(2)(+) and reionization of B(OH)(2) in the NR experiment are, however, associated with particularly unfavorable Franck-Condon factors. The differences in adiabatic and vertical electron transfer behavior can be traced back to a particular pi stabilization of the cationic species compared to the sp(2)-type neutral radical. Thermochemical data on several neutral and cationic boron compounds are presented based on calculations performed at the G2 level of theory.

4-Methoxyanilinium 2-carboxy-4,5-dichlorobenzoate

In the structure of the title salt C7H10NO+ C8H3Cl2O4- the benzene planes of the cation and anion are essentially parallel [inter-ring dihedral angle 4.8(2)deg]. In the anion the carboxylic acid and carboxylate groups make dihedral angles of 19.0(2) and 79.5(2)\%, respectively, with the benzene ring. Aminium N-H...O, carboxylic acid O-H...O and weak aromatic C-H...O hydrogen-bonding associations with carboxyl O-atom acceptors together with cation-anion pi-pi ring interactions [minimum ring centroid separation = 3.734(3)Ang] give a two-dimensional sheet structure which lies parallel to (001).

Anti-wind-up designs for dynamic positioning of marine vehicles with control allocation

This paper presents a framework for the design of a joint motion controller and a control allocation strategy for dynamic positioning of marine vehicles. The key aspects of the proposed designs are a systematic approach to deal with actuator saturation and to inform the motion controller about saturation. The proposed system uses a mapping that translates the actuator constraint sets into constraint sets at the motion controller level. Hence, while the motion controller addresses the constraints, the control allocation algorithm can solve an unconstrained optimisation problem. The constrained control design is approached using a multivariable anti-wind-up strategy for strictly proper controllers. This is applicable to the implementation of PI and PID type of motion controllers.

Mitigation of distorted and unbalanced stator voltage of stand-alone doubly fed induction generators using repetitive control technique

Unbalanced or non-linear loads result in distorted stator currents and electromagnetic torque pulsations in stand-alone doubly fed induction generators (DFIGs). This study proposes the use of a proportional-integral repetitive control (PIRC) scheme so as to mitigate the levels of harmonic and unbalance at the stator terminals of the DFIG. The PIRC is structurally simpler and requires much less computation than existing methods. Analysis of the PIRC operation and the methodology to determine the control parameters is included. Simulation study as well as laboratory test measurements demonstrate clearly the effectiveness of the proposed PIRC control scheme.

A mass spectrometry study of XCO+, X = Si, Ge : Is SiCO+ a main group carbonyl? Comments on the bonding in ground state SiCO and the Si,C,O (+) potential energy surface

The cation\[Si,C,O](+) has been generated by 1) the electron ionisation (EI) of tetramethoxysilane and 2) chemical ionisation (CI) of a mixture of silane and carbon monoxide. Collisional activation (CA) experiments performed for mass-selected \[Si,C,O](+), generated by using both methods, indicate that the structure is not inserted OSiC+; however, a definitive structural assignment as Si+-CO, Si+-OC or some cyclic variant is impossible based on these results alone. Neutralisation-reionisation (+NR+) experiments for EI-generated \[Si,C,O](+) reveal a small peak corresponding to SiC+, but no detectable SiO+ signal, and thus establishes the existence of the Si+-CO isomer. CCSD(T)//B3LYP calculations employing a triple-zeta basis set have been used to explore the doublet and quartet potential-energy surfaces of the cation, as well as some important neutral states The results suggest that both Si+-CO and Si+ - OC isomers are feasible; however, the global minimum is (2)Pi SiCO+. Isomeric (2)Pi SiOC+ is 12.1 kcal mol(-1) less stable than (2)Pi SiCO+, and all quartet isomers are much higher in energy. The corresponding neutrals Si-CO and Si-OC are also feasible, but the lowest energy Si - OC isomer ((3)A") is bound by only 1.5 kcal mol(-1). We attribute most, if nor all, of the recovery signal in the +NR' experiment to SiCO+ survivor ions. The nature of the bonding in the lowest energy isomers of Si+ -(CO,OC) is interpreted with the aid of natural bond order analyses, and the ground stale bonding of SiCO+ is discussed in relation to classical analogues such as metal carbonyls and ketenes.

Modeling and sensorless direct torque and flux control of a dual-airgap axial flux permanent-magnet machine with field-weakening operation

This paper presents the modeling and motion-sensorless direct torque and flux control of a novel dual-airgap axial-flux permanent-magnet machine optimized for use in flywheel energy storage system (FESS) applications. Independent closed-loop torque and stator flux regulation are performed in the stator flux ( x-y) reference frame via two PI controllers. This facilitates fast torque dynamics, which is critical as far as energy charging/discharging in the FESS is concerned. As FESS applications demand high-speed operation, a new field-weakening algorithm is proposed in this paper. Flux weakening is achieved autonomously once the y-axis voltage exceeds the available inverter voltage. An inherently speed sensorless stator flux observer immune to stator resistance variations and dc-offset effects is also proposed for accurate flux and speed estimation. The proposed observer eliminates the rotary encoder, which in turn reduces the overall weight and cost of the system while improving its reliability. The effectiveness of the proposed control scheme has been verified by simulations and experiments on a machine prototype.

Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Rapid analysis of GSTM1, GSTT1 and GSTP1 polymorphisms using real-time polymerase chain reaction

Polymorphisms of glutathione transferases (GST) are important genetic determinants of susceptibility to environmental carcinogens (Rebbeck, 1997). The GSTs are a multigene family of dimeric enzymes involved in detoxification, and, in a few cases, the bioactivation of a variety of xenobiotics (Hayes et al., 1995). The cytosolic GST enzyme family consists of four major classes of enzymes, referred to as alpha, mu, pi and theta. Several members of this family (for example, GSTM1, GSTT1 and GSTP1) are polymorphic in human populations (Wormhoudt et al., 1999). Molecular epidemiology studies have examined the role of GST polymorphisms as susceptibility factors for environmentally and/or occupationally induced cancers (Wormhoudt et al., 1999). In particular, case-control studies showed a relationship between the GSTM1 null genotype and the development of cancer in association with smoking habits, which has been shown for cancers of the respiratory and gastrointestinal tracts as well as other cancer types (Miller et al., 1997). Only a few molecular epidemiological studies addressed the role of GSTT1 and GSTP1 polymorphisms in cancer susceptibility. Since GSTP1 is a key player in biotransformation/bioactivation of benzo(a)pyrene, GSTP1 may be even more important than GSTM1 in the prevention of tobacco-induced cancers (Harries et al., 1997; Harris et al., 1998). To date, this relationship has not been sufficiently addressed in humans. Comprehensive molecular epidemiological studies may add to the current knowledge of the role of GST polymorphisms in cancer susceptibility and extent of the knowledge gained from approaches that used phenotyping, such as GSTM1 activity as it relates to trans-stilbene oxide, or polymerase chain reaction (PCR) based genotyping of polymorphic isoenzymes (Bell et al., 1993; Pemble et al., 1994; Harries et al., 1997).

Influence of polymorphisms of the human glutathione transferases and cytochrome P450 2E1 enzyme on the metabolism and toxicity of ethylene oxide and acrylonitrile

A cohort of 59 persons with industrial handling of low levels of acrylonitrile is being studied as part of a medical surveillance programme. Previously, an extended haemoglobin adduct monitoring (N-(cyanoethyl)valine and N-(hydroxyethyl)-valine) was performed regarding the glutathione transferases hGSTM1 and hGSTT1 polymorphisms but no influence of hGSTM1 or hGSTT1 polymorphisms on specific adduct levels was found. A compilation of case reports of human accidental poisonings had pointed to significant individual differences in human acrylonitrile metabolism and toxicity. Therefore, a re-evaluation of the industrial cohort included known polymorphisms of the glutathione transferases hGSTM3 and hGSTP1 as well as of the cytochrome P450 CYP2E1. A detailed statistical analysis revealed that exposed carriers of the allelic variants of hGSTP1, hGSTP1*B/hGSTP1*C, characterized by a single nucleotide polymorphism at nucleotide 313 which results in a change from Ile to Val at codon 104, had higher levels of the acrylonitrile-specific haemoglobin adduct N-(cyanoethyl)valine compared to the carriers of the codon 113 alleles hGSTP1*A and hGSTP1*D. The single nucleotide polymorphism at codon 113 of hGSTP1 (hGSTP1*A/hGSTP1*B versus hGSTP1*C/hGSTP1*D) did not show an effect, and also no influence was seen on specific haemoglobin adduct levels of the polymorphisms of hGSTM3 or CYP2E1. The data, therefore, point to a possible influence of a human enzyme polymorphism of the GSTP1 gene at codon 104 on the detoxication of acrylonitrile which calls for experimental toxicological investigation. The study also confirmed the impact of GSTT1 polymorphism on background N-(hydroxyethyl)-valine adduct levels in haemoglobin which are caused by endogenous ethylene oxide.

The quik fix study : a randomised controlled trial of brief interventions for young people with alcohol-related injuries and illnesses accessing emergency department and crisis support care

Background: Alcohol is a major preventable cause of injury, disability and death in young people. Large numbers of young people with alcohol-related injuries and medical conditions present to hospital emergency departments (EDs). Access to brief, efficacious, accessible and cost effective treatment is an international health priority within this age group. While there is growing evidence for the efficacy of brief motivational interviewing (MI) for reducing alcohol use in young people, there is significant scope to increase its impact, and determine if it is the most efficacious and cost effective type of brief intervention available. The efficacy of personality-targeted interventions (PIs) for alcohol misuse delivered individually to young people is yet to be determined or compared to MI, despite growing evidence for school-based PIs. This study protocol describes a randomized controlled trial comparing the efficacy and cost-effectiveness of telephone-delivered MI, PI and an Assessment Feedback/Information (AF/I) only control for reducing alcohol use and related harm in young people. Methods/design: Participants will be 390 young people aged 16 to 25 years presenting to a crisis support service or ED with alcohol-related injuries and illnesses (including severe alcohol intoxication). This single blinded superiority trial randomized young people to (i) 2 sessions of MI; (ii) 2 sessions of a new PI or (iii) a 1 session AF/I only control. Participants are reassessed at 1, 3, 6 and 12 months on the primary outcomes of alcohol use and related problems and secondary outcomes of mental health symptoms, functioning, severity of problematic alcohol use, alcohol injuries, alcohol-related knowledge, coping self-efficacy to resist using alcohol, and cost effectiveness. Discussion: This study will identify the most efficacious and cost-effective telephone-delivered brief intervention for reducing alcohol misuse and related problems in young people presenting to crisis support services or EDs. We expect efficacy will be greatest for PI, followed by MI, and then AF/I at 1, 3, 6 and 12 months on the primary and secondary outcome variables. Telephone-delivered brief interventions could provide a youth-friendly, accessible, efficacious, cost-effective and easily disseminated treatment for addressing the significant public health issue of alcohol misuse and related harm in young people. Trial registration: This trial is registered with the Australian and New Zealand Clinical Trials Registry ACTRN12613000108718.

Implementation and evaluation of open source unified communications for SMBs

Unified Communication (UC) is the integration of two or more real time communication systems into one platform. Integrating core communication systems into one overall enterprise level system delivers more than just cost saving. These real-time interactive communication services and applications over Internet Protocol (IP) have become critical in boosting employee accessibility and efficiency, improving customer support and fostering business agility. However, some small and medium-sized businesses (SMBs) are far from implementing this solution due to the high cost of initial deployment and ongoing support. In this paper, we will discuss and demonstrate an open source UC solution, viz. “Asterisk” for use by SMBs, and report on some performance tests using SIPp. The contribution from this research is the provision of technical advice to SMBs in deploying UC, which is manageable in terms of cost, ease of deployment and support.

Modeling and control of a CLC resonant dual active bridge

This paper proposes a linear large signal state-space model for a phase controlled CLC (Capacitor Inductor Capacitor) Resonant Dual Active Bridge (RDAB). The proposed model is useful for fast simulation and for the estimation of state variables under large signal variation. The model is also useful for control design because the slow changing dynamics of the dq variables are relatively easy to control. Simulation results of the proposed model are presented and compared to the simulated circuit model to demonstrate the proposed model's accuracy. This proposed model was used for the design of a Proportional-Integral (PI) controller and it has been implemented in the circuit simulation to show the proposed models usefulness in control design.