Dopaminergic Regulation of Glucose-induced Insulin Secretion through Dopamine D2 Receptors in the Pancreatic Islets In Vitro

The stimulatory effect of dopamine through dopamine 1)2 receptor on glucose - induced insulin secretion was studied in the pancreatic islets in nitro. I)oparnilie signifieanlly stimula(ed insulin secretion at a concentration of 10 a N1 in the presence of high,glucose ( 20 nii1 ). ' fhe higher concentrations of dopamine (111 -1() 4) inhibited glucose- induced insulin secretion in the presence of both 4 mM1 and 20 m M glucose. Stimulatory and inhibitory effect of dopamine on glucose - induced insulin secretion was reverted by the addition of dopamine 1)2 receptor antagonists such as butaclamol and sulpiride . Norepinephrine (NE) at 111 4 11 concentration inhibited the dopamine uptake as well as its stimulatory effect at 11) - 8 IN1 concentration on glucose induced insulin secretion. Our results suggest that dopamine exerts a differential effect on glucose -induced insulin secretion through dopamine D2 receptor and it is essential for the regulation of glucose-induced insulin secretion by pancreatic islets.

Industria y concentración de cultivos: la contribución de la industria del frío en la fruticultura leridana

Para avanzar en el estudio de la concentración espacial de cultivos, se ha elegido el caso de la manzana, la pera y el melocotón en Lleida, desde 1962 a 2000. La evolución de ese fenómeno se ha estudiado mediante técnicas de equilibrio espacial y análisis shift share, encontrándose una pauta espacial de comportamiento distinta entre la manzana y la pera por una parte y el melocotón por otro. En el caso de las técnicas shift share se ha modelado el efecto diferencial como el resultado de un juego de suma nula, y suponiendo que las transferencias de efectos son más probables hacia las regiones más cercanas, se ha avanzado una explicación de las transferencias de superficie que se produjeron entre 1962 y 2000. La diferencia encontrada en el distinto comportamiento espacial de esos cultivos se ha atribuido a la susceptibilidad de cada cultivo para ser conservado frigoríficamente. Se ha desarrollado un modelo que relaciona los incrementos de la capacidad en la industria frigorífica y de la superficie.

Effects of the Allosteric Antagonist 1-(4-Chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea (PSNCBAM-1) on CB1 Receptor Modulation in the Cerebellum

PSNCBAM-1 has recently been described as a cannabinoid CB1 receptor allosteric antagonist associated with hypophagic effects in vivo; however, PSNCBAM-1 effects on CB1 ligand-mediated modulation of neuronal excitability remain unknown. Here, we investigate PSNCBAM-1 actions on CB1 receptor-stimulated [35S]GTPγS binding in cerebellar membranes and on CB1 ligand modulation of presynaptic CB1 receptors at inhibitory interneurone-Purkinje cell (IN-PC) synapses in the cerebellum using whole-cell electrophysiology. PSNCBAM-1 caused non-competitive antagonism in [35S]GTPγS binding studies, with higher potency against the CB receptor agonist CP55940 than for WIN55,212-2 (WIN55). In electrophysiological studies, WIN55 and CP55940 reduced miniature inhibitory postsynaptic currents (mIPSCs) frequency, but not amplitude. PSNCBAM-1 application alone had no effect on mIPSCs; however, PSNCBAM-1 pre-treatment revealed agonist-dependent functional antagonism, abolishing CP55940-induced reductions in mIPSC frequency, but having no clear effect on WIN55 actions. The CB1 antagonist/inverse agonist AM251 increased mIPSC frequency beyond control, this effect was reversed by PSNCBAM-1. PSNCBAM-1 pre-treatment also attenuated AM251 effects. Thus, PSNCBAM-1 reduced CB1 receptor ligand functional efficacy in the cerebellum. The differential effect of PSNCBAM-1 on CP55940 versus WIN55 actions in [35S]GTPγS binding and electrophysiological studies and the attenuation of AM251 effects are consistent with the ligand-dependency associated with allosteric modulation. These data provide the first description of functional PSNCBAM-1 allosteric antagonist effects on neuronal excitability in the mammalian CNS. PSNCBAM-1 allosteric antagonism may provide viable therapeutic alternatives to orthosteric CB1 antagonists/inverse agonists in the treatment of CNS disease.

Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification

Background. Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method. The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results. Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions. Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

The role of myeloid receptors on murine plasmacytoid dendritic cells in induction of type I interferon

This study tested the hypothesis that a set of predominantly myeloid restricted receptors (F4/80, CD36, Dectin-1, CD200 receptor and mannan binding lectins) and the broadly expressed CD200 played a role in a key function of plasmacytoid DC (pDC), virally induced type I interferon (IFN) production. The Dectin-1 ligands zymosan, glucan phosphate and the anti-Dectin-1 monoclonal antibody (mAb) 2A11 had no effect on influenza virus induced IFNα/β production by murine splenic pDC. However, mannan, a broad blocking reagent against mannose specific receptors, inhibited IFNα/β production by pDC in response to inactivated influenza virus. Moreover, viral glycoproteins (influenza virus haemagglutinin and HIV-1 gp120) stimulated IFNα/β production by splenocytes in a mannan-inhibitable manner, implicating the function of a lectin in glycoprotein induced IFN production. Lastly, the effect of CD200 on IFN induction was investigated. CD200 knock-out macrophages produced more IFNα than wild-type macrophages in response to polyI:C, a MyD88-independent stimulus, consistent with CD200's known inhibitory effect on myeloid cells. In contrast, blocking CD200 with an anti-CD200 mAb resulted in reduced IFNα production by pDC-containing splenocytes in response to CpG and influenza virus (MyD88-dependent stimuli). This suggests there could be a differential effect of CD200 on MyD88 dependent and independent IFN induction pathways in pDC and macrophages. This study supports the hypothesis that a mannan-inhibitable lectin and CD200 are involved in virally induced type I IFN induction.

The identification of QTL controlling ergot sclerotia size in hexaploid wheat implicates a role for the Rht dwarfing alleles

The fungal pathogen Claviceps purpurea infects ovaries of a broad range of temperate grasses and cereals, including hexaploid wheat, causing a disease commonly known as ergot. Sclerotia produced in place of seed carry a cocktail of harmful alkaloid compounds that result in a range of symptoms in humans and animals, causing ergotism. Following a field assessment of C. purpurea infection in winter wheat, two varieties ‘Robigus’ and ‘Solstice’ were selected which consistently produced the largest differential effect on ergot sclerotia weights. They were crossed to produce a doubled haploid mapping population, and a marker map, consisting of 714 genetic loci and a total length of 2895 cM was produced. Four ergot reducing QTL were identified using both sclerotia weight and size as phenotypic parameters; QCp.niab.2A and QCp.niab.4B being detected in the wheat variety ‘Robigus’, and QCp.niab.6A and QCp.niab.4D in the variety ‘Solstice’. The ergot resistance QTL QCp.niab.4B and QCp.niab.4D peaks mapped to the same markers as the known reduced height (Rht) loci on chromosomes 4B and 4D, Rht-B1 and Rht-D1, respectively. In both cases, the reduction in sclerotia weight and size was associated with the semi-dwarfing alleles, Rht-B1b from ‘Robigus’ and Rht-D1b from ‘Solstice’. Two-dimensional, two-QTL scans identified significant additive interactions between QTL QCp.niab.4B and QCp.niab.4D, and between QCp.niab.2A and QCp.niab.4B when looking at sclerotia size, but not between QCp.niab.2A and QCp.niab.4D. The two plant height QTL, QPh.niab.4B and QPh.niab.4D, which mapped to the same locations as QCp.niab.4B and QCp.niab.4D, also displayed significant genetic interactions.

Sample stacking in CZE using dynamic thermal junctions I. Analytes with low dpK(a)/dT crossing a single thermally induced pH junction in a BGE with high dpH/dT

The possibility to compress analyte bands at the beginning of CE runs has many advantages. Analytes at low concentration can be analyzed with high signal-to-noise ratios by using the so-called sample stacking methods. Moreover, sample injections with very narrow initial band widths (small initial standard deviations) are sometimes useful, especially if high resolutions among the bands are required in the shortest run time. In the present work, a method of sample stacking is proposed and demonstrated. It is based on BGEs with high thermal sensitive pHs (high dpH/dT) and analytes with low dpK(a)/dT. High thermal sensitivity means that the working pK(a) of the BGE has a high dpK(a)/dT in modulus. For instance, Tris and Ethanolamine have dpH/dT = -0.028/degrees C and -0.029/degrees C, respectively, whereas carboxylic acids have low dpK(a)/dT values, i.e. in the -0.002/degrees C to+0.002/degrees C range. The action of cooling and heating sections along the capillary during the runs affects also the local viscosity, conductivity, and electric field strength. The effect of these variables on electrophoretic velocity and band compression is theoretically calculated using a simple model. Finally, this stacking method was demonstrated for amino acids derivatized with naphthalene-2,3-dicarboxaldehyde and fluorescamine using a temperature difference of 70 degrees C between two neighbor sections and Tris as separation buffer. In this case, the BGE has a high pH thermal coefficient whereas the carboxylic groups of the analytes have low pK(a) thermal coefficients. The application of these dynamic thermal gradients increased peak height by a factor of two (and decreased the standard deviations of peaks by a factor of two) of aspartic acid and glutamic acid derivatized with naphthalene-2,3-dicarboxaldehyde and serine derivatized with fluorescamine. The effect of thermal compression of bands was not observed when runs were accomplished using phosphate buffer at pH 7 (negative control). Phosphate has a low dpH/dT in this pH range, similar to the dK(a)/dT of analytes. It is shown that vertical bar dK(a)/dT-dpH/dT vertical bar >> 0 is one determinant factor to have significant stacking produced by dynamic thermal junctions.

Sample stacking in CZE using dynamic thermal junctions II: Analytes with high dpK(a)/dT crossing a single thermal junction in a BGE with low dpH/dT

In a previous work [M. Mandaji, et al., this issue] a sample stacking method was theoretically modeled and experimentally demonstrated for analytes with low dpK(a)/dT (analytes carrying carboxylic groups) and BGEs with high dpH/dT (high pH-temperature-coefficients). In that work, buffer pH was modulated with temperature, inducing electrophoretic mobility changes in the analytes. In the present work, the opposite conditions are studied and tested, i.e. analytes with high dpK(a)/dT and BGEs that exhibit low dpH/dT. It is well known that organic bases such as amines, imidazoles, and benzimidazoles exhibit high dpK(a)/dT. Temperature variations induce instantaneous changes on the basicity of these and other basic groups. Therefore, the electrophoretic velocity of some analytes changes abruptly when temperature variations are applied along the capillary. This is true only if BGE pH remains constant or if it changes in the opposite direction of pK(a) of the analyte. The presence of hot and cold sections along the capillary also affects local viscosity, conductivity, and electric field strength. The effect of these variables on electrophoretic velocity and band stacking efficacy was also taken into account in the theoretical model presented. Finally, this stacking method is demonstrated for lysine partially derivatized with naphthalene-2,3-dicarboxaldehyde. In this case, the amino group of the lateral chain was left underivatized and only the alpha amino group was derivatized. Therefore, the basicity of the lateral amino group, and consequently the electrophoretic mobility, was modulated with temperature while the pH of the buffer used remained unchanged.

Understanding the role of mediating risk factors and proxy effects in the association between socio-economic status and untreated hypertension

The association between socio-economic status (SES) and untreated hypertension varies according to a country's level of development and racial/ethnic group. We sought to confirm this variation in women from China and the United States (US) as well as to investigate the impact of SES on several mediating risk factors. We also investigate the extent to which SES explains racial/ethnic differences in untreated hypertension in the US. We used cross-sectional data from 1814 non-pregnant women in China (China Health and Nutrition Survey (CHNS), 1997) and 3266 non-pregnant women in the United States (National Health and Nutrition Examination Survey (NHANES III), 1988–1994) respectively. A variety of statistical modelling techniques was used to predict untreated hypertension as a function of several mediating factors and to simulate the impact of changes in SES. The age-adjusted prevalence of untreated hypertension was significantly higher (p<0.01) for low-income White and Black women compared to Mexican American or Chinese women. Untreated hypertension was not significantly associated with income or education in Mexican Americans or women in China. Obesity and light physical activity had the largest mediating effect on the association between SES and untreated hypertension for all racial/ethnic groups. However, this effect was not as strong as the proxy effect of income and education. SES did not completely explain racial/ethnic differences in hypertension in the US. While SES was more strongly associated with hypertension in Blacks than Whites, Blacks were still 1.97 (95% CI 1.47–2.64) times more likely to have untreated hypertension than Whites after adjusting for SES differences. The association between SES and untreated hypertension varied by country and racial/ethnic group. An important explanation for this variation was the differential effect of SES on mediating risk factors. SES disparities between Whites and Blacks in the US partly explain differences in the prevalence of untreated hypertension between these racial/ethnic groups.

Hyperstereopsis in helmet-mounted NVDs : absolute distance perception

Modern helmet-mounted night vision devices, such as the Thales TopOwl helmet, project imagery from intensifiers mounted on the side of the helmet onto the helmet faceplate. The increased separation of the cameras induces hyperstereopsis - the exaggeration of the stereoscopic disparities that support the perception of relative depth around the point of fixation. Increased camera separation may also affect absolute depth perception, because it increases the amount of vergence (crossing) of the eyes required for binocular fusion, and because the differential perspective from the viewpoints of the two eyes is increased. The effect of hyperstereopsis on the perception of absolute distance was investigated using a large-scale stereoscopic display system. A fronto-parallel textured surface was projected at a distance of 6 metres. Three stereoscopic viewing conditions were simulated - hyperstereopsis (four times magnification), normal stereopsis, and hypostereopsis (one quarter magnification). The apparent distance of the surface was measured relative to a grid placed in a virtual "leaf room" that provided rich monocular cues, such as texture gradients and linear perspective, to absolute distance as well as veridical sterescopic disparity cues. The different stereoscopic viewing conditions had no differential effect on the apparent distance of the textured surface at this viewing distance

Frequency-dependent physiological trade-offs between competing colour morphs

Evolutionary theory suggests that alternative colour morphs (i.e. genetically controlled phenotypes) may derive similar fitness under frequency-dependent selection. Here we experimentally demonstrate opposing effects of frequency-dependent social environments on plasma hormone levels (testosterone and corticosterone) and immune function between red- and black-headed male morphs of the Gouldian finch (Erythrura gouldiae). Red-headed males are highly sensitive to changes in the social environment, especially towards the relative density of their own aggressive morph, exhibiting high stress responses and immunosuppression in socially competitive environments. In contrast, the non-aggressive black-headed males follow a more passive strategy that appears to buffer them against social stresses. The differential effect of hormones on aggressive behaviour and immune performance reinforces the contrasting behavioural strategies employed by these colour morphs, and highlights the importance of the social environment in determining the individual basis of behavioural and physiological responses.

Investigation of the effects of microcomputers on the work of professional accountants

Information technology research over the past two decades suggests that the installation and use of computers fundamentally affects the structure and function of organisations and, m particular, the workers in these organizations. Following the release of the IBM Personal Computer in 1982, microcomputers have become an integral part of most work environments. The accounting services industry, in particular, has felt the impact of this ‘microcomputer revolution’. In Big Six accounting firms, there is almost one microcomputer for each professional accountant employed, Notwithstanding this, little research has been done on the effect of microcomputers on the work outcomes of professional accountants working in these firms. This study addresses this issue. It assesses, in an organisational setting, how accountant’ perceptions of ease of use and usefulness of microcomputers act on their computer anxieties, microcomputer attitudes and use to affect their job satisfaction and job performance. The research also examines how different types of human-computer interfaces affect the relationships between accountants' beliefs about microcomputer utility and ease of use, computer anxiety, microcomputer attitudes and microcomputer use. To attain this research objective, a conceptual model was first developed, The model indicates that work outcomes (job satisfaction and job performance) of professional accountants using microcomputers are influenced by users' perceptions of ease of use and usefulness of microcomputers via paths through (a) the level of computer anxiety experienced by users, (b) the general attitude of users toward using microcomputers, and (c) the extent to which microcomputers are used by individuals. Empirically testable propositions were derived from the model to test the postulated relationships between these constructs. The study also tested whether or not users of different human-computer interfaces reacted differently to the perceptions and anxieties they hold about microcomputers and their use in the workplace. It was argued that users of graphical interfaces, because of the characteristics of those interfaces, react differently to their perceptions and anxieties about microcomputers compared with users of command-line (or textual-based) interfaces. A passive-observational study in a field setting was used to test the model and the research propositions. Data was collected from 164 professional accountants working in a Big Six accounting firm in a metropolitan city in Australia. Structural equation modelling techniques were used to test the, hypothesised causal relationships between the components comprising the general research model. Path analysis and ordinary least squares regression was used to estimate the parameters of the model and analyse the data obtained. Multisample analysis (or stacked model analysis) using EQS was used to test the fit of the model to the data of the different human-computer interface groups and to estimate the parameters for the paths in those different groups. The results show that the research model is a good description of the data. The job satisfaction of professional accountants is directly affected by their attitude toward using microcomputers and by microcomputer use itself. However, job performance appears to be only directly affected by microcomputer attitudes. Microcomputer use does not directly affect job performance. Along with perceived ease of use and perceived usefulness, computer anxiety is shown to be an important determinant of attitudes toward using microcomputers - higher levels of computer anxiety negatively affect attitudes toward using microcomputers. Conversely, higher levels of perceived ease of use and perceived usefulness heighten individuals' positive attitudes toward using microcomputers. Perceived ease of use and perceived usefulness also indirectly affect microcomputer attitudes through their effect on computer anxiety. The results show that higher levels of perceived ease of use and perceived usefulness result in lower levels of computer anxiety. A surprising result from the study is that while perceived ease of use is shown to directly affect the level of microcomputer usage, perceived usefulness and attitude toward using microcomputers does not. The results of the multisample analysis confirm that the research model fits the stacked model and that the stacked model is a significantly better fit if specific parameters are allowed to vary between the two human-computer interface user groups. In general, these results confirm that an interaction exists between the type of human-computer interface (the variable providing the grouping) and the other variables in the model The results show a clear difference between the two groups in the way in which perceived ease of use and perceived usefulness affect microcomputer attitude. In the case of users of command-line interfaces, these variables appear to affect microcomputer attitude via an intervening variable, computer anxiety, whereas in the graphical interface user group the effect occurs directly. Related to this, the results show that perceived ease of use and perceived usefulness have a significant direct effect on computer anxiety in command-line interface users, but no effect at all for graphical interface users. Of the two exogenous variables only perceived ease of use, and that in the case of the command-line interface users, has a direct significant effect on extent of use of microcomputers. In summary, the research has contributed to the development of a theory of individual adjustment to information technology in the workplace. It identifies certain perceptions, anxieties and attitudes about microcomputers and shows how they may affect work outcomes such as job satisfaction and job performance. It also shows that microcomputer-interface types have a differential effect on some of the hypothesised relationships represented in the general model. Future replication studies could sample a broader cross-section of the microcomputer user community. Finally, the results should help Big Six accounting firms to maximise the benefits of microcomputer use by making them aware of how working with microcomputers affects job satisfaction and job performance.

Multi-scale modelling of DP590 steel

Dual Phase (DP) steel one of the Advanced High Strength Steels (AHSS) has a two phase microstructure where soft and hard phase acts together to offer a high strength composite effect. The high strength, however, must be balanced with ductility so that complex parts and designs can be manufactured from AHSS sheets. However, during forming certain grades of DP steel a sudden crack can occur without any intimation of necking. Thus, due to this abnormal forming behaviour, is difficult to accurately predict because most classical modelling approaches are not designed for such micro-structurally heterogeneous materials. These modelling approaches are generally based on an average representation of the material behaviour in a continuum mechanics formulation. This works for materials that are homogenous, or at least could be assumed to be homogenous at scales lower than the naked eye can see. However, for a material like AHSS, the microstructure plays a significant role in dictating the mechanical behaviour at the macro-scale. This paper studies the multi-scale modelling ofDP590 steel. It is found that the sufficient accuracy can be achieved from multi-scale modelling while comparing with the experiments.

Fracture of DP590 steel : a multi-scale modeling approach

Advanced high strength steel sheets are one of the higher strength advance material developed by the steel industry for automotive bodies. One of the categories of this advanced high strength steel is Dual Phase (DP) steel. This steel consists of a two phase microstructure where soft and hard phase acts together to offer a high strength composite effect. The combination of high strength and ductility exhibited by these sheets allows the design and manufacture of complex parts. However, during forming certain grades of DP steel sudden cracking can occur without any intimation of necking. This abnormal forming behavior is difficult to accurately predict because most classical modelling approaches are not designed for such micro-structurally heterogeneous materials. These modelling approaches are generally based on an average representation of the material behaviour in a continuum mechanics formulation. This works for materials that are homogenous, or at least could be assumed to be homogenous at scales lower than the naked eye can see. However, for a material like advanced high strength steel, the microstructure plays a significant role in dictating the mechanical behavior at the macro-scale. This paper studies the forming and fracture behavior through multi-scale modeling of DPO590 steel. It is found that the sufficient accuracy can be achieved from multi-scale modeling when comparing with experiments.

The impact of increasing course enrolment on student evaluation of teaching in engineering education

Student evaluation of teaching (SET) is important, commonplace and may be used in staff performance management. The SET literature suggests that class size is a negative systematic influence on SET ratings. In this paper we investigate time-series SET data from a large first-year engineering class where a decline in SET ratings was observed over time as course enrolment increased. We observe a negative halo effect of increasing class size on mean SET ratings and conclude that increasing course enrolment leads to a significant reduction in all mean SET ratings, even when the course learning design remains essentially unchanged. We also find an additional differential effect of increasing course enrolment on mean SET ratings. We observe that the marginal reduction in mean SET ratings for each additional student in the course enrolment is greater for those aspects of the student learning experience that are likely to be most directly impacted by increasing class size. We provide implications for practice from these findings.