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SA
Kinds of SA Terms modified by SA Selected AbstractsThe Differential Impacts of Early Physical and Sexual Abuse and Internalizing Problems on Daytime Cortisol Rhythm in School-Aged ChildrenCHILD DEVELOPMENT, Issue 1 2010Dante Cicchetti The impact of early physical and sexual abuse (EPA/SA) occurring in the first 5 years of life was investigated in relation to depressive and internalizing symptomatology and diurnal cortisol regulation. In a summer camp context, school-aged maltreated (n = 265) and nonmaltreated (n = 288) children provided morning and late afternoon saliva samples on 5 consecutive days. Child self-report and adult observer reports of child internalizing and depressive symptoms were obtained. Children experiencing EPA/SA and high depressive or internalizing symptoms uniquely exhibited an attenuated diurnal decrease in cortisol, indicative of neuroendocrine dysregulation. These results were specific to EPA/SA rather than later onset physical or sexual abuse or early occurring neglect or emotional maltreatment. [source] Converging free energy estimates: MM-PB(GB)SA studies on the protein,protein complex Ras,RafJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2004Holger Gohlke Abstract Estimating protein,protein interaction energies is a very challenging task for current simulation protocols. Here, absolute binding free energies are reported for the complex H-Ras/C-Raf1 using the MM-PB(GB)SA approach, testing the internal consistency and model dependence of the results. Averaging gas-phase energies (MM), solvation free energies as determined by Generalized Born models (GB/SA), and entropic contributions calculated by normal mode analysis for snapshots obtained from 10 ns explicit-solvent molecular dynamics in general results in an overestimation of the binding affinity when a solvent-accessible surface area-dependent model is used to estimate the nonpolar solvation contribution. Applying the sum of a cavity solvation free energy and explicitly modeled solute,solvent van der Waals interaction energies instead provides less negative estimates for the nonpolar solvation contribution. When the polar contribution to the solvation free energy is determined by solving the Poisson,Boltzmann equation (PB) instead, the calculated binding affinity strongly depends on the atomic radii set chosen. For three GB models investigated, different absolute deviations from PB energies were found for the unbound proteins and the complex. As an alternative to normal-mode calculations, quasiharmonic analyses have been performed to estimate entropic contributions due to changes of solute flexibility upon binding. However, such entropy estimates do not converge after 10 ns of simulation time, indicating that sampling issues may limit the applicability of this approach. Finally, binding free energies estimated from snapshots of the unbound proteins extracted from the complex trajectory result in an underestimate of binding affinity. This points to the need to exercise caution in applying the computationally cheaper "one-trajectory-alternative" to systems where there may be significant changes in flexibility and structure due to binding. The best estimate for the binding free energy of Ras,Raf obtained in this study of ,8.3 kcal mol,1 is in good agreement with the experimental result of ,9.6 kcal mol,1, however, further probing the transferability of the applied protocol that led to this result is necessary. © 2003 Wiley Periodicals, Inc. J Comput Chem 2: 238,250, 2003 [source] Application of the frozen atom approximation to the GB/SA continuum model for solvation free energyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2002Olgun Guvench Abstract The generalized Born/surface area (GB/SA) continuum model for solvation free energy is a fast and accurate alternative to using discrete water molecules in molecular simulations of solvated systems. However, computational studies of large solvated molecular systems such as enzyme,ligand complexes can still be computationally expensive even with continuum solvation methods simply because of the large number of atoms in the solute molecules. Because in such systems often only a relatively small portion of the system such as the ligand binding site is under study, it becomes less attractive to calculate energies and derivatives for all atoms in the system. To curtail computation while still maintaining high energetic accuracy, atoms distant from the site of interest are often frozen; that is, their coordinates are made invariant. Such frozen atoms do not require energetic and derivative updates during the course of a simulation. Herein we describe methodology and results for applying the frozen atom approach to both the generalized Born (GB) and the solvent accessible surface area (SASA) parts of the GB/SA continuum model for solvation free energy. For strictly pairwise energetic terms, such as the Coulombic and van-der-Waals energies, contributions from pairs of frozen atoms can be ignored. This leaves energetic differences unaffected for conformations that vary only in the positions of nonfrozen atoms. Due to the nonlocal nature of the GB analytical form, however, excluding such pairs from a GB calculation leads to unacceptable inaccuracies. To apply a frozen-atom scheme to GB calculations, a buffer region within the frozen-atom zone is generated based on a user-definable cutoff distance from the nonfrozen atoms. Certain pairwise interactions between frozen atoms in the buffer region are retained in the GB computation. This allows high accuracy in conformational GB comparisons to be maintained while achieving significant savings in computational time compared to the full (nonfrozen) calculation. A similar approach for using a buffer region of frozen atoms is taken for the SASA calculation. The SASA calculation is local in nature, and thus exact SASA energies are maintained. With a buffer region of 8 Å for the frozen-atom cases, excellent agreement in differences in energies for three different conformations of cytochrome P450 with a bound camphor ligand are obtained with respect to the nonfrozen cases. For various minimization protocols, simulations run 2 to 10.5 times faster and memory usage is reduced by a factor of 1.5 to 5. Application of the frozen atom method for GB/SA calculations thus can render computationally tractable biologically and medically important simulations such as those used to study ligand,receptor binding conformations and energies in a solvated environment. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 214,221, 2002 [source] Calculation of ligand-nucleic acid binding free energies with the generalized-born model in DOCKBIOPOLYMERS, Issue 2 2004Xinshan Kang Abstract The calculation of ligand-nucleic acid binding free energies is investigated by including solvation effects computed with the generalized-Born model. Modifications of the solvation module in DOCK, including introduction of all-atom parameters and revision of coefficients in front of different terms, are shown to improve calculations involving nucleic acids. This computing scheme is capable of calculating binding energies, with reasonable accuracy, for a wide variety of DNA-ligand complexes, RNA-ligand complexes, and even for the formation of double-stranded DNA. This implementation of GB/SA is also shown to be capable of discriminating strong ligands from poor ligands for a series of RNA aptamers without sacrificing the high efficiency of the previous implementation. These results validate this approach to screening large databases against nucleic acid targets. © 2003 Wiley Periodicals, Inc. Biopolymers 73:192,204, 2004 [source] Genetic and epigenetic changes in aberrant crypt foci and serrated polypsCANCER SCIENCE, Issue 6 2008Yutaka Suehiro Aberrant crypt foci (ACF) in colorectal mucosa are the earliest known morphological precursors to colorectal cancer and can be subclassified as dysplastic, heteroplastic (non-dysplastic), and mixed types. Serrated adenoma (SA) is a polyp with serrated architecture and dysplasia, and can be subclassified as traditional SA or sessile SA. Sessile SA is thought to be preneoplastic and differs from most lesions in the traditional SA category because of their flat morphology and general lack of cytological dysplasia. Serrated polyps include hyperplastic polyps (HP), SA, and admixed hyperplastic-adenomatous polyps and are considered a morphological continuum encompassing heteroplastic ACF, HP, admixed hyperplastic-adenomatous polyps, and SA. Recent studies have uncovered other developmental pathways including a heteroplastic ACF-HP/SA-carcinoma sequence and a heteroplastic ACF,adenoma,carcinoma sequence. Heteroplastic ACF histopathologically resemble HP and SA. Sporadic HP are usually present in the left colon, are small, and are considered benign. However, adenocarcinoma arising in the setting of colorectal HP or SA, especially in patients with hyperplastic polyposis, has been described. The relationship between heteroplastic ACF, HP, and colorectal cancer is less certain than that of dysplastic ACF. Here, we discuss the current understanding of genetic and epigenetic alterations in the development of colorectal cancer. Our goal is to provide a conceptual framework for understanding the heteroplastic ACF,HP/SA,carcinoma sequence. (Cancer Sci 2008; 99: 1071,1076) [source] Characterization of natural wax esters by MALDI-TOF mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2009Vladimír Vrkoslav Abstract The applicability of matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) to the analysis of wax esters (WEs) was investigated. A series of metal salts of 2,5-dihydroxybenzoic acid (DHB) was synthesized and tested as possible matrices. Alkali metal (Li, Na, K, Rb, Cs) and transition metal (Cu, Ag) salts were studied. The matrix properties were evaluated, including solubility in organic solvents, threshold laser power that should be applied for successful desorption/ionization of WEs, the nature of the matrix ions and the mass range occupied by them, and the complexity of the isotope clusters for individual metals. Lithium salt of dihydroxybenzoic acid (LiDHB) performed the best and matrices with purified lithium isotopes (6LiDHB or 7LiDHB) were recommended for WEs. Three sample preparation procedures were compared: (1) mixing the sample and matrix in a glass vial and deposition of the mixture on a MALDI plate (Mix), (2) deposition of sample followed by deposition of matrix (Sa/Ma), and (3) deposition of matrix followed by deposition of sample (Ma/Sa). Morphology of the samples was studied by scanning electron microscopy. The best sample preparation technique was Ma/Sa with the optimum sample to matrix molar ratio 1 : 100. Detection limit was in the low picomolar range. The relative response of WEs decreased with their molecular weight, and minor differences between signals of saturated and monounsaturated WEs were observed. MALDI spectra of WEs showed molecular adducts with lithium [M + Li]+. Fragments observed in postsource decay (PSD) spectra were related to the acidic part of WEs [RCOOH + Li]+ and they were used for structure assignment. MALDI with LiDHB was used for several samples of natural origin, including insect and plant WEs. A good agreement with GC/MS data was achieved. Moreover, MALDI allowed higher WEs to be analyzed, up to 64 carbon atoms in Ginkgo biloba leaves extract. Copyright © 2008 John Wiley & Sons, Ltd. [source] Hybrid Meta-Heuristic Algorithm for the Simultaneous Optimization of the O,D Trip Matrix EstimationCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 6 2004Antony Stathopoulos These include a genetic algorithm (GA), a simulated annealing (SA) algorithm, and a hybrid algorithm (GASA) based on the combination of GA and SA. The computational performance of the three algorithms is evaluated and compared by implementing them on a realistic urban road network. The results of the simulation tests demonstrate that SA and GASA produce a more accurate final solution than GA, whereas GASA shows a superior convergence rate, that is, faster improvement from the initial solution, in comparison to SA and GA. In addition, GASA produces a final solution that is more robust and less dependent on the initial demand pattern, in comparison to that obtained from a greedy search algorithm. [source] Circulatory effects of apnoea in elite breath-hold diversACTA PHYSIOLOGICA, Issue 1 2009F. Joulia Abstract Aim:, Voluntary apnoea induces several physiological adaptations, including bradycardia, arterial hypertension and redistribution of regional blood flows. Elite breath-hold divers (BHDs) are able to maintain very long apnoea, inducing severe hypoxaemia without brain injury or black-out. It has thus been hypothesized that they develop protection mechanisms against hypoxia, as well as a decrease in overall oxygen uptake. Methods:, To test this hypothesis, the apnoea response was studied in BHDs and non-divers (NDs) during static and dynamic apnoeas (SA, DA). Heart rate, arterial oxygen saturation (SaO2), and popliteal artery blood flow were recorded to investigate the oxygen-conserving effect of apnoea response, and the internal carotid artery blood flow was used to examine the mechanisms of cerebral protection. Results:, The bradycardia and peripheral vasoconstriction were accentuated in BHDs compared with NDs (P < 0.01), in association with a smaller SaO2 decrease (,2.7% vs. ,4.9% during SA, P < 0.01 and ,6% vs. ,11.3% during DA, P < 0.01). Greater increase in carotid artery blood flow was also measured during apnoea in BHDs than in controls. Conclusion:, These results confirm that elite divers present a potentiation of the well-known apnoea response in both SA and DA conditions. This response is associated with higher brain perfusion which may partly explain the high levels of world apnoea records. [source] Panic and suicidal ideation and suicide attempts: results from the National Comorbidity SurveyDEPRESSION AND ANXIETY, Issue 3 2006M.P.H., Renee D. Goodwin Ph.D. Abstract Our objective was to determine the association between panic attacks (PAs) and panic disorder (PD), and suicidal ideation (SI) and suicide attempts (SAs) in a nationally representative sample of adults in the community. Data were drawn from the National Comorbidity Survey (n=5,877), a representative household sample of adults ages 15,54 in the United States. Multiple logistic regression analyses were used to examine the relationship between current and lifetime PA and PD and SI and SA, adjusting for differences in demographic characteristics, comorbid mental disorders (major depression, alcohol dependence, and substance dependence), childhood trauma (physical and sexual abuse), and number of lifetime mental disorders. Past-year and lifetime PA and PD were associated with increased SI (both past year and lifetime), and persisted after adjusting for comorbidity and early trauma. Associations between PA and SA were no longer statistically significant after adjusting for comorbidity. Past-year and lifetime PD were associated with lifetime SA, but these associations were no longer statistically significant after adjusting for comorbidity. Past-year and lifetime PD were associated with past-year SA, and this association persisted after adjusting for demographics, comorbidity, and number of lifetime mental disorders. These findings are consistent with previous results, and further help to clarify the relationships between panic and suicide behavior by identifying potential methodological reasons for inconsistencies in results from previous studies. Depression and Anxiety 23:124,132, 2006. © 2006 Wiley-Liss, Inc. [source] Dopamine transporter gene (DAT1) VNTR polymorphism in major psychiatric disorders: family-based association study in the Bulgarian populationACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002L. Georgieva Objective:,A 40-bp variable number tandem repeat in the 3,-UTR of dopamine transporter gene (DAT1) has been examined for association with major psychiatric disorders in several case,control studies. No significant results have been found. We used a new collection of parent,offspring trios to test for association with schizophrenia (SZ), bipolar 1 disorder (BPI) and schizoaffective (SA) disorder. Method:,We genotyped trios from Bulgarian origin where the proband had SZ (178 trios), BPI (77 trios) and SA (29 trios). Alleles ranging from 5 to 11 repeats were observed. The results were analysed with the extended TDT (ETDT). Results:,No preferential transmission of alleles was observed for any diagnostic group. The presence of allele DAT*10 was associated with the severity and frequency of auditory hallucinations, however, this result is not significant if corrected for multiple testing. Conclusion:,Our results are in agreement with previous reports of a lack of association between this polymorphism and major psychiatric disorders. [source] Risk factors for suicide attempts in patients with alcohol dependence or abuse and a history of depressive symptoms: A subgroup analysis from the WHO/ISBRA studyDRUG AND ALCOHOL REVIEW, Issue 1 2010ÖZGÜR YALDIZLI Abstract Introduction and Aims. Alcoholism, depression and suicide attempts (SA) are strongly interrelated. The aims were to determine risk factors and develop a prognostic predictor model for SA in a subgroup of patients with a history of alcohol dependence or abuse and depressive symptoms. Design and Methods. A subgroup analysis from the data of the World Health Organisation (WHO)/the International Society for Biomedical Research on Alcoholism (ISBRA)-collaborative study on biological state and trait marker of alcohol use and dependence, an international multi-centre study with a cross-sectional design, based on a standardised questionnaire. We analysed from 1314 variables 43 factors,including demographic characteristics, dependence variables, comorbid disorders, personality trait markers and family history,that were supposed to be most predictive for SA according to the literature. Correlation analyses by the ,2 -test and Mann,Whitney U -test were performed to obtain statistical meaningful parameters for logistic regression analysis. Results. Of the 1863 persons included in the WHO/ISBRA study, 292 had both a history of depressive symptoms and alcohol dependence or abuse and were included in the subgroup analysis. In the logistic regression analysis, drinking status, depressive symptoms, adverse drinking experiences during alcohol consumption, bad experiences from drug abuse and antidepressant therapy were found to be independent risk factors for SA. Positive family history of alcoholism was a model-improving co-factor. This predictive model explains approximately 60% of the variance (Nagelkerkes' square). Discussion and Conclusions. This prognostic model derived from data of the WHO/ISBRA collaborative study shows important risk factors for SA in patients with history of alcohol abuse or dependence and depressive symptoms. [ Yaldizli Ö, Kuhl HC, Graf M, Wiesbeck GA, Wurst FM. Risk factors for suicide attempts in patients with alcohol dependence or abuse and a history of depressive symptoms: A subgroup analysis from the WHO/ISBRA study. Drug Alcohol Rev 2009] [source] Multiobjective heuristic approaches to seismic design of steel frames with standard sectionsEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 11 2007M. Ohsaki Abstract Seismic design problem of a steel moment-resisting frame is formulated as a multiobjective programming problem. The total structural (material) volume and the plastic dissipated energy at the collapse state against severe seismic motions are considered as performance measures. Geometrically nonlinear inelastic time-history analysis is carried out against recorded ground motions that are incrementally scaled to reach the predefined collapse state. The frame members are chosen from the lists of the available standard sections. Simulated annealing (SA) and tabu search (TS), which are categorized as single-point-search heuristics, are applied to the multiobjective optimization problem. It is shown in the numerical examples that the frames that collapse with uniform interstorey drift ratios against various levels of ground motions can be obtained as a set of Pareto optimal solutions. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effect of sialic acid content on glycoprotein pI analyzed by two-dimensional electrophoresisELECTROPHORESIS, Issue 17 2010Sílvia Barrabés Abstract 2-DE is broadly used for quantitative analysis of differential protein expression in complex mixtures such as serum samples or cell lysates. PTMs directly influence the 2-DE pattern, and knowledge of the rules of protein separation is required in order to understand the protein distribution in a 2-DE gel. Glycosylation is the most common PTM and can modify both the molecular weight and the pI of a protein. In particular, the effect of charged monosaccharides (mainly sialic acids, SAs) on the 2-DE pattern of a protein is of major interest since changes in sialylation are regularly observed in comparative studies. Little is known about the pI shift of a glycoprotein induced by the presence of SAs, or whether this shift is the same for all glycoproteins. To address this issue, this study examined the influence of SA on the 2-DE pattern of three serum glycoproteins (haptoglobin, ,1-antitrypsin and ribonuclease 1), which N -glycan chains had been previously characterised, and reviewed existing bibliographic data. The SA content of the different glycoforms of a glycoprotein showed a negative linear correlation with the pI, although the slope varied among the studied glycoproteins. We also described a positive correlation between the protein pI and the pI decrease per SA molecule. [source] Development of HPLC and NACE methods for the simultaneous determination of benzoic and sorbic acids in sour snap beans containing oilELECTROPHORESIS, Issue 22 2007Po Han Abstract The practical methods were developed for the simultaneous determination of benzoic acid (BA) and sorbic acid (SA) in sour snap bean samples containing oil. BA and SA in the samples were extracted by ultrasonication with water, followed by cleanup procedures with precipitation for removing the potential proteins and with petroleum ether liquid,liquid extraction for removing the edible oil contained in the samples. The HPLC method was developed using Supelco C18 (250,mm×4.6,mm id, 5,,m) as column, MeOH,20,mM NH4Ac (25:75 v/v) at 1.0,mL/min as the mobile phase and 230,nm as the detection wavelength. The optimal NACE method was established with a running buffer of 20.0,mM NH4Ac in 95% MeOH (pH*,10.6), and an applied voltage of ,30,kV over a capillary of 50,,m id×48.5,cm (40,cm to the detector window), which gave a baseline separation of BA and SA, and as well as of the blank matrix within ca. 10,min. Both HPLC and NACE methods gave the relatively lower limits of quantification at about 0.01,0.02 and 0.04,0.05,mg/kg, respectively, whereas the overall recoveries were larger than 85.0%. The proposed methods have been successfully applied to measure 15 real sour bean samples and the content profile of BA and SA in sour bean samples was obtained and evaluated. [source] Effects of a sustained heroin shortage in three Australian StatesADDICTION, Issue 7 2005Louisa Degenhardt ABSTRACT Background In early 2001 in Australia there was a sudden and dramatic decrease in heroin availability that occurred throughout the country that was evidenced by marked increases in heroin price and decreases in its purity. Aim This study examines the impact of this change in heroin supply on the following indicators of heroin use: fatal and non-fatal drug overdoses; treatment seeking for heroin dependence; injecting drug use; drug-specific offences; and general property offences. The study was conducted using data from three Australian States [New South Wales (NSW), Victoria (VIC) and South Australia (SA)]. Methods Data were obtained on fatal and non-fatal overdoses from hospital emergency departments (EDs), ambulance services and coronial systems; treatment entries for heroin dependence compiled by State health departments; numbers of needles and syringes distributed to drug users; and data on arrests for heroin-related incidents and property-related crime incidents compiled by State Police Services. Time-series analyses were conducted where possible to examine changes before and after the onset of the heroin shortage. These were supplemented with information drawn from studies involving interviews with injecting drug users. Results After the reduction in heroin supply, fatal and non-fatal heroin overdoses decreased by between 40% and 85%. Despite some evidence of increased cocaine, methamphetamine and benzodiazepine use and reports of increases in harms related to their use, there were no increases recorded in the number of either non-fatal overdoses or deaths related to these drugs. There was a sustained decline in injecting drug use in NSW and VIC, as indicated by a substantial drop in the number of needles and syringes distributed (to 1999 levels in Victoria). There was a short-lived increase in property crime in NSW followed by a sustained reduction in such offences. SA and VIC did not show any marked change in the categories of property crime examined in the study. Conclusions Substantial reductions in heroin availability have not occurred often, but in this Australian case a reduction had an aggregate positive impact in that it was associated with: reduced fatal and non-fatal heroin overdoses; reduced the apparent extent of injecting drug use in VIC and NSW; and may have contributed to reduced crime in NSW. All these changes provide substantial benefits to the community and some to heroin users. Documented shifts to other forms of drug use did not appear sufficient to produce increases in deaths, non-fatal overdoses or treatment seeking related to those drugs. [source] Spindles-Inducing Mechanism Modulates Sleep Activation of Interictal Epileptiform Discharges in the Landau,Kleffner SyndromeEPILEPSIA, Issue 2 2000L. Nobili Summary: Purpose: Landau,Kleffner syndrome (LKS) is characterized by a marked increase of interictal epileptiform discharges (IEDs) during sleep. During nonrapid eye movement (NREM) sleep, neuronal membrane potential oscillations lead to the appearance of spindles and delta waves in the surface EEG and might develop into paroxysmal synchronization. Spectral analysis allows the quantitative description of the dynamics of delta (slow-wave activity, SWA, 0.5-4.5 Hz) and sigma activity (SA, 12.0,16.0 Hz) and can be used to assess the relation between SA, SWA, and IEDs during sleep. Methods: We performed six overnight continuous EEG-polysomnographic studies in three patients with LKS. The temporal series of SWA and SA were obtained from a spike-free derivation lead. The IEDs count was performed on the most active lead. Relations between sigma and SWA and time series of lEDs were tested by means of correlation techniques after data normalization. Results: Our results revealed a significantly higher correlation between IEDs and SA with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between SA and IEDs. Conclusions: Our data suggest that neural mechanisms involved in the generation of sleep spindles facilitate IEDs production in LKS. [source] Preliminary study of mucosal IgA in the equine small intestine: specific IgA in cases of acute grass sickness and controlsEQUINE VETERINARY JOURNAL, Issue 5 2007F. G. NUNN Summary Reasons for performing study: There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state. Objectives: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract of horses and to relate antibody levels to disease status. Methods: Samples of tissue (n = 25: 6 duodenum, 7 jejunum and 12 ileum) were taken from acute grass sickness (AGS) cases and from control horses (n = 12; 4 samples from each site) at post mortem. They were extracted with the detergent saponin in the presence of protease inhibitors and assayed for total IgA, for specific IgA against botulinum neurotoxins types C and D (BoNT/C or BoNT/D), and against surface antigens of a BoNT/C negative strain of C. botulinum type C (SA) and of Clostridium tetani (TetSA), as a control. Specific IgA was expressed as percentage total IgA. Results: Compared to controls, significantly higher levels of specific IgA against BoNT/C were detected in the jejunum (P = 0.04) and ileum (P = 0.02) of AGS cases. Similarly, higher specific levels against BoNT/D were demonstrated in duodenum (P = 0.01) and jejunum (P = 0.02). Significantly higher levels of IgA against SA were demonstrated only in duodenal samples (P = 0.01). Conclusions: Levels of IgA antibody to BoNTs in control horses were at near undetectable levels, suggesting no recent exposure to toxins. In AGS cases, significantly higher levels of specific IgA were detected predominantly in jejunum and ileum. Potential relevance: If specific IgA is protective then any successful vaccine for EGS should induce a mucosal response. [source] Verification of skin-based markers for 3-dimensional kinematic analysis of the equine tarsal jointEQUINE VETERINARY JOURNAL, Issue 8 2004S. KHUMSAP Summary Reasons for performing study: Kinematic studies are usually based on tracking markers attached to the skin. However, complex joints, such as the tarsal joint, function in 3-dimensions (3D), and have therefore necessitated application of the invasive bone pin technique, limiting kinematic studies to the research laboratory. This study investigates the feasibility of using skin-based markers for 3D analysis of tarsal joint motion. Hypothesis: Three-dimensional motions of the tarsal joint can be measured with an acceptable degree of accuracy using skin markers. Methods: Retroreflective markers were attached over the tibial and metatarsal segments. Markers were tracked automatically at trot. Three-dimensional skin correction algorithms were used for correction of skin displacement, and 3D motions derived from the corrected (CSD) and uncorrected (USD) skin displacement were compared with data from a previous study in which those motions were described using bone-fixed markers (BFM) by correlation, root mean square errors (RMS) and shape agreement (SA) of the curves. Results: The RMS of BFM and CSD were smaller than those of BFM and USD for all motions. The correlation coefficients of BFM and CSD were higher than those of BFM and USD. SA was good or fair for all motions except internal/external rotation and medial/lateral translation. Conclusions and potential relevance: With appropriate correction for skin movement relative to skeletal landmarks, skin markers can identify tarsal 3D motions for flexion/extension, abduction/adduction, cranial/caudal translation, and proximal/distal translation, allowing analysis and comparison of information between horses during swing and stance phases. [source] Increased coronary sinus blood temperature: correlation with systemic inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2006K. Toutouzas Abstract Background, Recent studies have shown that patients with single vessel coronary artery disease (CAD) suffering from acute coronary syndromes (ACS) have increased coronary sinus (CS) blood temperature compared with the right atrium (RA). The aim of this study was to investigate whether there is a correlation between systemic inflammatory indexes and CS temperature and whether there is a difference in CS temperature between patients with single vs. multivessel disease. Materials and methods, We included consecutive patients scheduled for coronary angiography for recent-onset chest pain evaluation. We measured C-reactive protein (CRP) levels in the study population. Coronary sinus and RA blood temperature measurements were performed by a 7F thermography catheter. ,, was calculated by subtracting the RA from the CS blood temperature. Results, The study population comprised 53 patients with ACS, 25 patients with stable angina (SA) and 22 subjects without CAD (control group). ,, was greater in patients with ACS and with SA compared with the control group (0·22 ± 0·10 °C, 0·18 ± 0·04 °C vs. 0·14 ± 0·07 °C, P < 0·01 for both comparisons). The ACS group had greater ,, compared with the SA group, although the difference did not reach statistical significance (P = 0·09). Eighteen (39·1%) out of 46 patients with multivessel disease had three-vessel disease and 28 (60·8%) had two-vessel disease. ,, between patients with multivessel and single vessel disease was similar (0·22 ± 0·01 °C, 0·19 ± 0·01 °C, P = 0·17). The levels of CRP were well correlated with ,, (R = 0·35b, P < 0·01). Conclusions, Systemic inflammation is well correlated with CS temperature; thus, an inflammatory process could be the underlying mechanism for increased heat production from the myocardium. [source] Different pathophysiological mechanisms of intramitochondrial iron accumulation in acquired and congenital sideroblastic anemia caused by mitochondrial DNA deletionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2006Thomas Matthes Abstract:, Sideroblastic anemias (SA) are characterized by iron accumulation in the mitochondria of erythroblasts. Although we have evidence of mitochondrial gene alterations in sporadic congenital cases, the origin of acquired forms [refractory anemia with ring sideroblasts (RARS)], is still largely unknown. Here, we report the analysis of respiratory chain function in a patient with a large mitochondrial deletion and in patients with RARS. A young boy with SA showed symptoms typical of a mitochondrial disease with metabolic acidosis, muscle weakness and cerebral involvement. His bone marrow DNA was analyzed for the presence of mitochondrial deletions. We found a new mitochondrial (mt)DNA deletion spanning 3614 bp and including all the mt genes encoding complex IV, plus ATPase 6 and 8, and several transfer (t)RNAs. All tissues analyzed (liver, skeletal muscle, brain, pancreas) showed a heteroplasmic distribution of this mutant DNA. Bone marrow homogenates were obtained from five patients with RARS and from three patients with normal bone marrow and respiratory chain function assayed by spectrophotometric analysis. Cytochrome c oxidase (CCO) activity was greatly reduced in the patient's bone marrow. In contrast, CCO activity and global respiratory chain function were conserved in patients with RARS. We conclude that deficient CCO activity secondary to mtDNA deletions is related to intramitochondrial iron accumulation, as in our patient or in those with Pearson's syndrome, whereas other mechanisms, e.g. nuclear DNA mutations, have to be proposed to be involved in the acquired forms of SA. [source] PRECLINICAL STUDY: Mifepristone and spironolactone differently alter cocaine intravenous self-administration and cocaine-induced locomotion in C57BL/6J miceADDICTION BIOLOGY, Issue 1 2010Jean-François Fiancette ABSTRACT Corticosterone, the main glucorticoid hormone in rodents, facilitates behavioral responses to cocaine. Corticosterone is proposed to modulate cocaine intravenous self-administration (SA) and cocaine-induced locomotion through distinct receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), respectively. However, this remains debatable. On one hand, modulation of both responses by the GR was tested in different experimental conditions, i.e. light versus dark nycthemeral phase and naïve versus cocaine-experienced animals. On the other hand, modulation of both responses by the MR was never tested directly but only inferred based on the ability of low plasma corticosterone levels (those for which corticosterone almost exclusively binds the MR) to compensate the effects of adrenalectomy. Our goal here was to test the involvement of the GR and the MR in cocaine-induced locomotor and reinforcing effects in the same experimental conditions. C57Bl/6J mice were trained for cocaine (1 mg/kg/infusion) intravenous SA over 40 SA sessions. The animals were then administered with mifepristone (30 mg/kg i.p.), a GR antagonist, or with spironolactone (20 mg/kg/i.p.), an MR antagonist, 2 hours before either cocaine intravenous SA or cocaine-induced locomotion. In a comparable nycthemeral period and in similarly cocaine-experienced animals, a blockade of the GR decreased cocaine-induced reinforcing effects but not cocaine-induced locomotion. A blockade of the MR decreased both cocaine-induced reinforcing (but to a much lesser extent than the GR blockade) and locomotor effects. Altogether, our results comforted the hypothesis that the GR modulates cocaine-related operant conditioning, while the MR would modulate cocaine-related unconditioned effects. The present data also reveal mifepristone as an interesting tool for manipulating the impact of corticosterone on cocaine-induced reinforcing effects in mice. [source] Sleep disruption, daytime somnolence and ,sleep attacks' in Parkinson's disease: a clinical survey in PD patients and age-matched healthy volunteersEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2006J. J. Ferreira Recent case reports of ,sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10,3). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention. [source] Reduced saccadic resilience and impaired saccadic adaptation due to cerebellar diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Heidrun Golla Abstract The term short-term saccadic adaptation (STSA) captures our ability to unconsciously move the endpoint of a saccade to the final position of a visual target that has jumped to a new location during the saccade. STSA depends on the integrity of the cerebellar vermis. We tested the hypothesis that STSA reflects the working of a cerebellar mechanism needed to avoid ,fatigue', a gradual drop in saccade amplitude during a long series of stereotypic saccades. To this end we compared the kinematics of saccades of 14 patients suffering from different forms of cerebellar disease with those of controls in two tests of STSA and a test of saccadic resilience. Controls showed an increase in saccade amplitude (SA) for outward adaptation, prompted by outward target shifts, due to an increase in saccade duration (SD) in the face of constant peak velocity (PV). The decrease in SA due to inward adaptation was, contrariwise, accompanied by a drop in PV and SD. Whereas patients with intact vermis did not differ from controls, those with vermal pathology lacked outward adaptation: SD remained constant, as did SA and PV. In contrast, vermal patients demonstrated a significant decrease in SA, paralleled by a decrease in PV but mostly unaltered SD in the inward adaptation experiment as well as in the resilience test. These findings support the notion that inward adaptation is at least partially based on uncompensated fatigue. On the other hand, outward adaptation reflects an active mechanism for the compensation of fatigue, residing in the cerebellum. [source] Surface Physiochemistry Affects Protein Adsorption to Stoichiometric and Silicate-Substituted Microporous Hydroxyapatites,ADVANCED ENGINEERING MATERIALS, Issue 4 2010Katharina Guth An important factor in the bioactivity and success of a bone-graft substitute is the nature of the adsorbed protein layer, which plays a vital role in orchestrating cell attachment and development through the presence of adhesion proteins such as fibronectin (Fn) and vitronectin (Vn). In this study, microporous hydroxyapatite (HA) and silicate-substituted hydroxyapatite (SA) discs with matched porosity and surface morphology are developed to mimic the topography found in commercial bone-graft substitutes in order to identify whether the introduction of microporosity and associated surface roughness eliminates the beneficial effect that silicate substitution has on protein adsorption. The introduction of microporosity does not abolish the relative enrichment of the protein layer that is adsorbed to the microporous SA discs, as opposed to HA, but appears to accelerate it. Fibronectin and Vn adsorption in a range of competitive environments at physiological temperatures confirm that the microporous SA discs have a greater affinity for Fn and Vn compared with HA, suggesting differences in the mechanisms behind the surface affinity to SA. Thus, development of a surface protein layer on SA and HA is likely to be dependent on the nature of the local protein environment and a combination of factors that are associated with the addition of silicate: the surface charge, the nature of the ionic species at the interface and the resultant hydrophilicity of the surface. Total protein adsorption is not found to be a good indicator of potential implant performance, particularly at early time points. [source] Effect of Silicate-Substitution on Attachment and Early Development of Human Osteoblast-Like Cells Seeded on Microporous Hydroxyapatite Discs,ADVANCED ENGINEERING MATERIALS, Issue 1-2 2010Katharina Guth Hydroxyapatite (HA) is a well-established graft material used in bone repair. Silicon-substituted hydroxyapatite (SA; 0.8,wt% Si) has shown greater bone ingrowth and bone coverage than phase pure HA. To assess the effect of microporosity on sensitivity of cell attachment to surface physiochemistry, microporous SA and HA discs, and control Thermanox (TMX) discs were incubated with osteoblast-like cells (5,×,104 HOS-TE85 cells) under differing tissue culture conditions. To investigate early cellular attachment, organization, and differentiation, cells were also stained for integrin,,5,1, actin, and runt-related transcription factor (RUNX-2), respectively, after incubation on HA, SA, and TMX discs for 3 days. No significant differences emerged between HA, SA, and TMX discs in mean numbers of cells attached in serum free medium (SFM) over 90,min incubation. In contrast, significantly more cells were attached to SA than HA after 180,min incubation in complete medium (C-MEM) containing fetal calf serum (p,<,0.05). Cell attachment to SA and HA discs pre-conditioned in SFM supplemented with fibronectin (FN) was lower than discs pre-conditioned in C-MEM, suggesting sensitivity of an active FN conformation to the presence of co-adsorbates. Confocal microscopy demonstrated significantly more co-localization of integrin ,5,1 and actin on SA than HA. Translocalization of RUNX-2 to the nucleus was stronger in cells incubated on SA. Microporosity did not diminish the effect of surface physiochemistry on cell adhesion, and enhanced cell attachment for SA appears to be mediated by differences in the quality of adsorbed protein rather than via direct effects of substrate chemistry. [source] A Concise and Efficient Synthesis of seco -Duocarmycin SAEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2003Lutz F. Tietze Abstract A short and efficient synthesis of seco -duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5- exo - trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] ,Seek and ye shall find': antecedents of assimilation and contrast in social comparisonEUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 5 2001Thomas Mussweiler Based on a Selective Accessibility (SA) model of comparison consequences, it is suggested that the self-evaluative effects of social comparisons depend on the nature of the hypothesis that is tested as a starting-point of the comparison process. If judges test the hypothesis that they are similar to the standard, then standard-consistent self-knowledge is rendered accessible so that self-evaluations are assimilated towards the standard. If judges test the hypothesis that they are dissimilar from the standard, however, standard-inconsistent self-knowledge is made accessible so that self-evaluations are contrasted away from the standard. These predictions are tested by inducing participants to test for similarity versus dissimilarity to the standard via a procedural priming manipulation. Consistent with the SA model, assimilation occurs if participants are procedurally primed to focus on similarities to the standard, whereas contrast results if they are primed to focus on dissimilarities. These findings suggest that similarity versus dissimilarity testing is a crucial determinant of assimilation versus contrast. It is proposed that distinguishing between these two alternative hypotheses may provide an integrative framework for an understanding of the self-evaluative consequences of social comparisons. Copyright © 2001 John Wiley & Sons, Ltd. [source] Optimal measurement placement for security constrained state estimation using hybrid genetic algorithm and simulated annealingEUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 2 2009T. Kerdchuen Abstract This paper proposes a hybrid genetic algorithm and simulated annealing (HGS) for solving optimal measurement placement for power system state estimation. Even though the minimum number of measurement pairs is N considering the single measurement loss, their positions are required to make the system observable. HGS algorithm is a genetic algorithm (GA) using the acceptance criterion of simulated annealing (SA) for chromosome selection. The P, observable concept is used to check the network observability with and without single measurement pair loss contingency and single branch outage. Test results of 10-bus, IEEE 14, 30, 57, and 118-bus systems indicate that HGS is superior to tabu search (TS), GA, and SA in terms of higher frequency of the best hit and faster computational time. Copyright © 2007 John Wiley & Sons, Ltd. [source] Quantitative evaluation of severity in psoriatic lesions using three-dimensional morphometryEXPERIMENTAL DERMATOLOGY, Issue 4 2004Sang Yong Park Abstract:, The severity of psoriasis has been traditionally assessed by measures, such as the psoriasis area and severity index (PASI), the psoriasis severity scores, and the lesional severity scores. As a result, even experienced dermatologists show variations when attempting to determine the severity of psoriasis. Therefore, a better non-invasive and objective measurement of clinical signs is needed. In this study, an instrument, a so-called ,stereoimage optical topometer' (SOT), based on a new concept of ,stereoimaging' was used to measure the three-dimensional skin surface. The aim of this study was to compare the results obtained by the SOT with the visual score of psoriasis lesion. Thirty psoriatic patients were enrolled in this study. Initially, the severity of the infiltration and the scale of 134 psoriatic lesions were assessed by using a visual scoring system (0: none, 1: mild, 2: moderate, 3: severe, and 4: very severe), as scored by five dermatologists. The SOT was then used to quantify the severity of each psoriatic lesion using four three-dimensional SOT parameters (Sa, SL, SA, and SV). Secondly, the involved skin-surface area in the psoriasis cases was scored by the naked eye by the five dermatologists and by image analysis. Statistically significant differences were observed between grades 0, 1, 2, and 3 in terms of the severity measurements of the individual psoriatic lesions by SOT when using the parameters Sa, SL, SA, and SV. Therefore, it was concluded that there is a strong correlation between the results measured by visual scoring and by SOT in psoriasis. [source] Corrosion fatigue behaviour of a 15Cr-6Ni precipitation-hardening stainless steel in different tempersFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 6 2000C.-K. Lin Systematic fatigue experiments, including both high-cycle axial fatigue (S,N curves) and fatigue crack growth (FCG, da/dN,,K curves), were performed on a precipitation-hardening martensitic stainless steel in laboratory air and 3.5 wt% NaCl solution. Specimens were prepared in three tempers, i.e. solution-annealed (SA), peak-aged (H900) and overaged (H1150) conditions, to characterize the effects of ageing treatment on the corrosion fatigue (CF) resistance. S,N results indicated that fatigue resistance in all three tempers was dramatically reduced by the aqueous sodium chloride environment. In addition, the smooth-surface specimens in H900 temper exhibited longer CF lives than the H1150 ones, while those in SA condition stood in between. However, for precracked specimens, the H1150 temper provided superior corrosive FCG resistance than the other two tempers. Comparison of the S,N and FCG curves indicated that early growth of crack-like defects and short cracks played the major role in determining the CF life for smooth surface. The differences in the CF strengths for the S,N specimens of the given three tempers were primarily due to their inherent differences in resistance to small crack growth, as they were in the air environment. [source] | ||||||||||||||||||||||||||||||||||||||||||||||