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Greater Sensitivity (greater + sensitivity)
Selected AbstractsA review of molecular techniques to type Candida glabrata isolatesMYCOSES, Issue 6 2010S. Abbes Summary Candida glabrata has emerged as a common cause of fungal infection causing mucosal and systemic infections. This yeast is of concern because of its reduced antifungal susceptibility to azole antifungals such as fluconazole. A clear understanding of the epidemiology of Candida infection and colonisation required a reliable typing system for the evaluation of strain relatedness. In this study, we discuss the different molecular approaches for typing C. glabrata isolates. Recent advances in the use of molecular biology-based techniques have enabled investigators to develop typing systems with greater sensitivities. Several molecular genotypic approaches have been developed for fast and accurate identification of C. glabrata in vitro. These techniques have been widely used to study diverse aspects such as nosocomial transmission. Molecular typing of C. glabrata could also provide information on strain variation, such as microvariation and microevolution. [source] A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet functionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000De Miguel Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source] Trait emotional intelligence: behavioural validation in two studies of emotion recognition and reactivity to mood inductionEUROPEAN JOURNAL OF PERSONALITY, Issue 1 2003K. V. Petrides This paper presents two experiments concerning trait emotional intelligence (,trait EI'). In study 1, ten high and ten low trait EI individuals were selected from a sample of 85 persons to participate in a computerized experiment involving the recognition of morphed emotional expressions. As hypothesized, high trait EI participants were faster at identifying the expressions than their low trait EI counterparts. In study 2, trait EI scores from 102 persons were residualized on the Big Five and subsequently 15 high and 15 low trait EI individuals were selected to participate in a mood induction experiment. As hypothesized, high trait EI participants exhibited greater sensitivity to the mood induction procedure than their low trait EI counterparts. The findings are discussed in terms of the construct validity of trait EI, with particular emphasis on the issue of incremental validity vis-à-vis broad personality traits. Copyright © 2002 John Wiley & Sons, Ltd. [source] Responses to hedonically conflicting social comparisons: comparing happy and unhappy peopleEUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 5 2001Sonja Lyubomirsky Two laboratory studies explored how self-rated unhappy and happy students balance hedonically conflicting social comparison information, and tested whether unhappy students would be relatively more sensitive to hedonically consistent unfavorable information. In both studies, students working in teams of four competed against one other team on a novel verbal task. First, unhappy participants showed relatively greater sensitivity to undiluted unfavorable feedback,about group standing (e.g. your team ,lost'; Study 1) and about group and individual standing (e.g. your team lost and you were placed last; Study 2). Second, unhappy students were more reactive than happy students to individual social comparison information in the context of relative group feedback. In Study 1, the moods and self-assessments of unhappy individuals (but not happy ones) after news of team defeat appeared to be buffered by the additional news of personal triumph. In Study 2, unhappy students showed relatively larger decreases in mood and ability assessments after unfavorable than after favorable individual feedback (i.e. ranking last versus first), regardless of whether they additionally learned that their teams had won or lost. The role of students' attributions and perceptions of their personal contribution was also explored. Implications of these findings for the links among social comparison, cognitive processes, and hedonic consequences are discussed. Copyright © 2001 John Wiley & Sons, Ltd. [source] A cocaine insensitive chimeric insect serotonin transporter reveals domains critical for cocaine interactionFEBS JOURNAL, Issue 16 2002Sumandeep K. Sandhu Serotonin transporters are key target sites for clinical drugs and psychostimulants, such as fluoxetine and cocaine. Molecular cloning of a serotonin transporter from the central nervous system of the insect Manduca sexta enabled us to define domains that affect antagonist action, particularly cocaine. This insect serotonin transporter transiently expressed in CV-1 monkey kidney cells exhibits saturable, high affinity Na+ and Cl, dependent serotonin uptake, with estimated Km and Vmax values of 436 ± 19 nm and 3.8 ± 0.6 × 10,18 mol·cell·min,1, respectively. The Manduca high affinity Na+/Cl, dependent transporter shares 53% and 74% amino acid identity with the human and fruit fly serotonin transporters, respectively. However, in contrast to serotonin transporters from these two latter species, the Manduca transporter is inhibited poorly by fluoxetine (IC50 = 1.23 µm) and cocaine (IC50 = 12.89 µm). To delineate domains and residues that could play a role in cocaine interaction, the human serotonin transporter was mutated to incorporate unique amino acid substitutions, detected in the Manduca homologue. We identified a domain in extracellular loop 2 (amino acids 148,152), which, when inserted into the human transporter, results in decreased cocaine sensitivity of the latter (IC50 = 1.54 µm). We also constructed a number of chimeras between the human and Manduca serotonin transporters (hSERT and MasSERT, respectively). The chimera, hSERT1,146/MasSERT106,587, which involved N-terminal swaps including transmembrane domains (TMDs) 1 and 2, was remarkably insensitive to cocaine (IC50 = 180 µm) compared to the human (IC50 = 0.431 µm) and Manduca serotonin transporters. The chimera MasSERT1,67/hSERT109,630, which involved only the TMD1 swap, showed greater sensitivity to cocaine (IC50 = 0.225 µm) than the human transporter. Both chimeras showed twofold higher serotonin transport affinity compared to human and Manduca serotonin transporters. Our results show TMD1 and TMD2 affect the apparent substrate transport and antagonist sensitivity by possibly providing unique conformations to the transporter. The availability of these chimeras facilitates elucidation of specific amino acids involved in interactions with cocaine. [source] Cooler temperatures increase sensitivity to ultraviolet B radiation in embryos and larvae of the frog Limnodynastes peroniiGLOBAL CHANGE BIOLOGY, Issue 6 2007VINCENT O. Van UITREGT Abstract Recent studies suggest that complex interacting processes are driving global amphibian declines. Increased ultraviolet B (UVB) radiation in the solar spectrum associated with ozone depletion has been implicated in declines, and evidence suggests that the effects of UVB radiation on amphibians may be greater at cooler temperatures. We tested the thermal sensitivity of UVB effects on amphibians in a controlled factorial experiment using the striped marsh frog, Limnodynastes peronii as a model species. We compared survival, growth and locomotor performance of embryonic and larval L. peronii reared under low and high UVB exposures at both 20 and 30 °C. Embryonic and larval L. peronii proved extremely sensitive to UVB damage and exhibited greater sensitivity at 20 °C compared with 30 °C. Embryonic survival to Gosner stage 25 was unaffected by UVB exposure at 30 °C, but at 20 °C survival was reduced to 52% under high UVB. Larval survival exhibited a similar trend. At 20 °C, all tadpoles survived under low UVB, whereas under high UVB there was 100% mortality after 15 days of exposure. At 30 °C, 86% survived under low UVB, but only 46% survived under high UVB. Sublethal effects such as, embryonic malformation, retarded larval growth and reduced larval swimming performance were also greater at 20 °C compared with 30 °C. Our results strongly indicate that UVB damage in amphibians is markedly increased at cooler temperatures. Thus, populations of UVB sensitive species occurring at cold climates may be at greater risk of declines due to increased solar UVB radiation. [source] Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease,,HEPATOLOGY, Issue 4 2007Aldo J. Montano-Loza Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end-stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens. Fourteen of 214 patients (7%) failed corticosteroid treatment. Patients who failed therapy were younger (33 ± 3 years versus 48 ± 1 years, P = 0.0008), had higher serum levels of bilirubin at accession (4.1 ± 0.9 mg/dL versus 2.3 ± 0.2 mg/dL, P = 0.02), presented acutely more frequently (43% versus 14%, P = 0.01), and had a higher frequency of HLA (human leukocyte antigen) DRB1*03 (93% versus 53%, P = 0.004) than did patients who achieved remission. An alternative disease (fatty liver disease) emerged in only 1 patient who failed therapy (7%). Scores determined by the model of end-stage liver disease at presentation of patients who failed treatment were higher than those of who achieved remission (16 ± 1 versus 10 ± 0.3 points, P < 0.0001), and score greater than 12 points had greater sensitivity (97%) and specificity (68%) for treatment failure than did HLA DRB1*03 or other features. Conclusion: Onset at an early age, acute presentation, hyperbilirubinemia, and presence of HLA DRB1*03 characterize patients who fail corticosteroid treatment. The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome. (HEPATOLOGY 2007.) [source] A gene-alteration profile of human lung cancer cell lines,HUMAN MUTATION, Issue 8 2009Raquel Blanco Abstract Aberrant proteins encoded from genes altered in tumors drive cancer development and may also be therapeutic targets. Here we derived a comprehensive gene-alteration profile of lung cancer cell lines. We tested 17 genes in a panel of 88 lung cancer cell lines and found the rates of alteration to be higher than previously thought. Nearly all cells feature inactivation at TP53 and CDKN2A or RB1, whereas BRAF, MET, ERBB2, and NRAS alterations were infrequent. A preferential accumulation of alterations among histopathological types and a mutually exclusive occurrence of alterations of CDKN2A and RB1 as well as of KRAS, epidermal growth factor receptor (EGFR), NRAS, and ERBB2 were seen. Moreover, in non-small-cell lung cancer (NSCLC), concomitant activation of signal transduction pathways known to converge in mammalian target of rapamycin (mTOR) was common. Cells with single activation of ERBB2, PTEN, or MET signaling showed greater sensitivity to cell-growth inhibition induced by erlotinib, LY294002, and PHA665752, respectively, than did cells featuring simultaneous activation of these pathways, underlining the need for combined therapeutic strategies in targeted cancer treatments. In conclusion, our gene-alteration landscape of lung cancer cell lines provides insights into how gene alterations accumulate and biological pathways interact in cancer. Hum Mutat 30,1,8, 2009. © 2009 Wiley-Liss, Inc. [source] The effects of early relational antecedents and other factors on the parental sensitivity of mothers and fathersINFANT AND CHILD DEVELOPMENT, Issue 1 2003Diane Pelchat Abstract This study examines the effect of early relational antecedents (ERA, i.e. the quality of parenting parents recalled receiving as children), parenting stress, marital stress, socio-economic factors and children's characteristics (gender and disability condition) on the parental sensitivity of mothers and fathers. The sample consisted of 116 mothers and 84 fathers of 117 eighteen month old children drawn from a larger longitudinal study on the adaptation of parents to a child with a disability. Thirty-four children were diagnosed with Down syndrome (DS), 51 with a cleft lip and/or palate (CLP), and 32 were non-disabled children. Multiple regression analyses reveal that mothers' sensitivity is best predicted by her level of education and family income, whereas fathers' sensitivity is best predicted by their ERA, marital stress, family income and the child's disability condition. Mothers with more education and a greater family income displayed a greater sensitivity to their children, as did fathers who perceive less marital stress, those with a greater family income and those who perceived their parents as less controlling. Also, fathers of children with DS displayed less sensitivity for their children than fathers of children with CLP or fathers of non-disabled children. These results concord with many studies about the importance of socio-economic factors, ERA, marital stress, parent's gender and children's factors in the understanding of parental sensitivity. Copyright © 2003 John Wiley & Sons, Ltd. [source] Intrinsic chemotherapy resistance to the tubulin-binding antimitotic agents in renal cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Roisean E. Ferguson Abstract Renal cancer is one of the most chemoresistant tumor types. Using a panel of 10 established renal cancer cell lines that have not been subjected to prior drug selection, the range of functional resistance phenotypes to the tubulin-binding agents paclitaxel, vinblastine, vincristine and patupilone (epothilone B, EPO906) was determined, together with expression of P-glycoprotein (PgP), multidrug resistance associated protein-2 (MRP2) and major vault protein (MVP) proteins. The IC50 values for vincristine correlated positively with PgP expression (r = 0.73; p = 0.031), with values for paclitaxel and vinblastine just failing to reach significance. A significant positive correlation was observed for sensitivity to paclitaxel and MRP2 expression only (r = 0.8; p = 0.013). MVP expression did not correlate with sensitivity to any of the drugs examined. All cell lines exhibited much greater sensitivity to patupilone, demonstrating for the first time the potential use of patupilone in this cancer. In tissue samples from chemotherapy-naive renal cell carcinoma (RCC) patients, marked downregulation or absence of PgP in many tumor cells with expression levels more similar to sensitive cell lines rather than the resistant lines was seen. Similarly, MRP2 was absent or only weakly present in tumor cells, whereas MVP was very strongly upregulated in most tumor samples. This study illustrating discrepancies between results exclusively based on studies in cell lines and findings in vivo suggests that the role of PgP and MRP2 in intrinsic resistance in RCC in vivo may be less than expected from the in vitro findings and supports a potential role for MVP on the basis of in vivo expression studies. © 2004 Wiley-Liss, Inc. [source] Alkaline phosphatase activity in pasteurized milk: A quantitative comparison of Fluorophos and colourimetric proceduresINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 3 2009CLARE PAYNE Fluorophos and colourimetric procedures for alkaline phosphatase (ALP) testing were compared using milk with raw milk additions, purified bovine ALP additions and heat treatments. Repeatability was between 0.9% and 10.1% for Fluorophos, 3.5% and 46.1% for the Aschaffenburg and Mullen (A&M) procedure and 4.4% and 8.8% for the Scharer rapid test. Linearity (,R2) using raw milk addition was 0.96 between Fluorophos and the Scharer procedure. Between the Fluorophos and the A&M procedures, R2 values were 0.98, 0.99 and 0.98 for raw milk additions, bovine ALP additions and heat treatments respectively. Fluorophos showed greater sensitivity and was both faster and simpler to perform. [source] Quantification of dental caries by osteologists and odontologists,a validity and reliability study,INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2010C. Liebe-Harkort Abstract As in modern populations, dental caries in early populations is linked to diet and general health. In order to record not only advanced disease states with frank cavitation of teeth but also early lesions, indicating the presence of the disease in a population, it is important that the archaeologist can correctly detect and classify lesions of varying severity. The present study compares and contrasts quantification of dental caries by osteologists and odontologists. Four osteologists and four odontologists undertook visual and radiographic inspection of 61 teeth from three different sources: medieval, 19th century and modern. Separate sets of criteria were applied to disclose observer confidence in detecting a lesion and in estimating lesion extent. For validation of visual assessments, the teeth were sectioned. Radiographic assessments were validated by a specialist in dental radiography. The results disclosed that the odontologists in general showed greater sensitivity than the osteologists, correctly identifying carious lesions, but the osteologists had higher specificity, correctly identifying healthy teeth. Thus, the osteologists tend to overlook carious lesions (under-diagnosis), while the odontologists tend to incorrectly record lesions in healthy teeth (over-diagnosis). For both osteologists and odontologists, correct assessment was poorer for radiographs than for visual inspection. Copyright © 2009 John Wiley & Sons, Ltd. [source] Occurrence and molecular genotyping of Cryptosporidium spp. in surface waters in Northern IrelandJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2001C.J. Lowery Aims: To investigate the incidence and genotype of Cryptosporidium parvum oocysts in drinking water sources in Northern Ireland for the period 1996,1999, and to compare conventional and molecular methods of detection. Methods and Results: Four hundred and seventy-four waters were investigated by conventional methods, namely immuno-fluorescent antibody detection (IFA; 380) and immuno-magnetic separation-IFA (IMS-IFA; 94), of which 14/474 (3%) were positive. Two hundred and fourteen samples (214/474) were also investigated by PCR techniques, targeting both the 18S rRNA and TRAP-C2 genes, of which 11/214 (5·1%) were positive. These 11 samples were classified as genotype II following sequence analysis of the TRAP-C2 amplicon. Conclusions: This study demonstrated the low incidence of oocysts of C. parvum in water sources in Northern Ireland. Significance and Impact of the Study: Such molecular-based techniques offer a number of advantages over conventional detection methodologies, namely greater sensitivity and specificity as well as the ability to provide accurate genotyping data rapidly, which may be valuable in directing operational management in potential outbreak situations. [source] Detection of cryptosporidia and Cryptosporidium parvum oocysts in environmental water samples by immunomagnetic separation,polymerase chain reactionJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2000S. Hallier-Soulier Cryptosporidium parvum has emerged as one of the most important new contaminants found in drinking water. Current protocols for the detection of cryptosporidia are time-consuming and rather inefficient. We recently described an immunomagnetic separation,polymerase chain reaction (IMS,PCR) assay permitting highly sensitive detection of C. parvum oocysts in drinking water samples. In this study, a second IMS,PCR assay to detect all cryptosporidial oocysts was developed, and both IMS,PCR assays were optimized on river water samples. A comparative study of the two IMS,PCR assays and the classical detection method based on an immunofluorescence assay (IFA) was carried out on 50 environmental samples. Whatever the type of water sample, the discrepancy in C. parvum detection between the IFA and IMS,PCR took the form of IFA-negative/IMS,PCR-positive results, and was caused mainly by the greater sensitivity of IMS,PCR as compared with IFA. Of the 50 water samples, only five tested positive for C. parvum using IMS,PCR, and could constitute a threat to human health. These results show that both IMS,PCR assays provide a rapid (1 d) and sensitive means of screening environmental water samples for the presence of cryptosporidia and C. parvum oocysts. [source] Fluctuating asymmetry of sexual and nonsexual traits in stalk-eyed flies: a poor indicator of developmental stress and genetic qualityJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2000Bjorksten It has been proposed that females use fluctuating asymmetry (FA) in sexual ornaments to assess male quality. FA of sexual traits is predicted to show greater sensitivity to stress than FA of nonsexual traits, and to be heritable. We used a half-sib mating design and manipulation of larval food environment to test these predictions on stalk-eyed flies, Cyrtodiopsis dalmanni, in which females prefer males with larger eyespans. We measured size and FA of eyestalks and of two nonsexually selected characters, wing length and width. We found no evidence of an increase in FA under larval food stress in any of the individual traits, although trait size decreased under stress. We combined FA across traits into a single composite index, and found that males reared in the most benign larval environment had significantly higher composite FA than males reared on other media. There was no such effect in females. Heritability of FA was not significantly different from zero in any of the traits, in any of the environments, although trait sizes showed high heritability. We conclude that FA in sexual and nonsexual traits is a poor indicator of developmental stress and genetic quality. [source] Self-Serving Attributions in Corporate Annual Reports: A Replicated StudyJOURNAL OF MANAGEMENT STUDIES, Issue 1 2002Eric W. K. Tsang This study is a replication of Bettman and Weitz (1983) in the Singapore context. Data from Letters to Shareholders in 208 annual reports published in 1985 and 1994 were used to analyse the patterns of causal explanations for corporate performance outcomes. The general self-serving pattern of attributions found in the original study was also identified in this study. However, the data of the original study do not unequivocally support either the motivational or informational explanation for the existence of self-serving attributions, whereas the latter explanation is strongly supported by the data of this study. This finding is consistent with the growing evidence provided by cross-cultural psychological research indicating East Asians' greater sensitivity to situational influences when making causal attributions. In short, the present study clearly illustrates the important role of replication in the knowledge accumulation and theory development of strategy research. [source] DEVELOPING CULTURALLY EFFECTIVE FAMILY-BASED RESEARCH PROGRAMS: IMPLICATIONS FOR FAMILY THERAPISTSJOURNAL OF MARITAL AND FAMILY THERAPY, Issue 3 2004William L. Turner Recently, some family scholars have developed greater sensitivity to the relative neglect of families of color in clinical and empirical research. Consequently, a proliferation of research elucidating many nuances of ethnic families has come to the forefront, containing a wealth of knowledge with useful implications for family therapists and other mental health providers. The findings of these studies hold enormously important implications for how family therapists can better engage and accommodate families of color in therapy: In this article we discuss some of the etiological and methodological issues associated with planning, conducting, and disseminating family-based prevention and intervention research programs with ethnic minority families. [source] Protein identification by peptide mass fingerprinting and peptide sequence tagging with alternating scans of nano-liquid chromatography/infrared multiphoton dissociation Fourier transform ion cyclotron resonance mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2003Toshiyuki Kosaka Abstract We have developed a method for protein identification with peptide mass fingerprinting and sequence tagging using nano liquid chromatography (LC)/Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). To achieve greater sensitivity, a nanoelectrospray (nano-ES) needle packed with reversed-phase medium was used and connected to the nano-ES ion source of the FTICR mass spectrometer. To obtain peptide sequence tag information, infrared multiphoton dissociation (IRMPD) was carried out in nano-LC/FTICR-MS analysis. The analysis involves alternating nano-ES/FTICR-MS and nano-ES/IRMPD-FTICR-MS scans during a single LC run, which provides sets of parent and fragment ion masses of the proteolytic digest. The utility of this alternating-scan nano-LC/IRMPD-FTICR-MS approach was evaluated by using bovine serum albumin as a standard protein. We applied this approach to the protein identification of rat liver diacetyl-reducing enzyme. It was demonstrated that this enzyme was correctly identified as 3-,-hydroxysteroid dehydrogenase by the alternating-scan nano-LC/IRMPD-FTICR-MS approach with accurate peptide mass fingerprinting and peptide sequence tagging. Copyright © 2003 John Wiley & Sons, Ltd. [source] Conceptualizing and evaluating career successJOURNAL OF ORGANIZATIONAL BEHAVIOR, Issue 2 2005Peter A. Heslin Within the vast literature on the antecedents of career success, the success criterion has generally been operationalized in a rather deficient manner. Several avenues for improving the conceptualization and measurement of both objective and subjective career success are identified. Paramount among these is the need for greater sensitivity to the criteria that study participants, in different contexts, use to construe and judge their career success. This paper illustrates that contextual and individual factors are likely to be associated with the relative salience of objective and subjective criteria of career success. Drawing on social comparison theory, propositions are also offered about when self- and other-referent success criteria are likely to be most salient. A broader research agenda addresses career success referent choice, organizational interventions, and potential cultural differences. This article maps out how future research can be more sensitive to how people actually do conceptualize and evaluate their own career success. Copyright © 2005 John Wiley & Sons, Ltd. [source] Characterization of amorphous solids with weak glass transitions using high ramp rate differential scanning calorimetryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2008Derrick S. Katayama Abstract Measurement of the glass transition temperature (Tg) of proteins and other high molecular weight polymers in the amorphous state is often difficult, since the transition is extremely weak, that is, the ,Cp at the glass transition temperature is small. For example, little is known about the solid-state properties of hydroxyethyl starch (HES), which is beginning to become more commonly evaluated as a bulking agent in pharmaceutical products. For weak thermal events, such as the change in heat capacity at the Tg of a pure protein or large synthetic polymer, increased heating rate should produce greater sensitivity in terms of heat flow. Recent innovations in rapid scanning technology for differential scanning calorimetry (DSC) allow measurements on materials where the thermal events are difficult to detect by conventional DSC. In the current study, measurements of the Tg of proteins in the solid state, amorphous pharmaceutical excipients which have small ,Cp at the glass transition temperature, and bacterial spores, have all been made using high ramp rate DSC, providing information on materials that was inaccessible using conventional DSC methods. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1013,1024, 2008 [source] EFFECTIVENESS OF CATEGORY AND LINE SCALES TO CHARACTERIZE CONSUMER PERCEPTION OF FRUITY FERMENTED FLAVOR IN PEANUTSJOURNAL OF SENSORY STUDIES, Issue 2 2006J.L. GREENE ABSTRACT Fruity fermented (FF) flavor is a common off-flavor in peanuts resulting from high-temperature curing. The 9-point hedonic scale is the most widely used scale to determine consumer acceptance; however, research has indicated that line scales may provide equal reliability and greater sensitivity. The objectives of this study were to characterize consumer perception of FF flavor in peanuts and to compare the effectiveness of the two scale types. Consumers (n = 208) evaluated control (no FF), low-intensity (1.0) FF and high-intensity (3.0) FF peanut pastes for the strength/intensity of roasted peanut flavor (RPF), sweet taste (ST), fresh peanut flavor (FPF) and overall liking (OV) using randomly assigned ballots. Sensitivity in defining consumer perception of off-flavor in peanuts was greater with use of line scales than with the hedonic scale. The line scale indicated that FF flavor in peanuts, even at low intensity, negatively impacted OV and further identified significantly lower RPF and FPF perception by consumers. The hedonic scale identified only a difference in FPF and was not sensitive enough to show a difference in OV. [source] N -methyl-d-aspartate Receptor Responses Are Differentially Modulated by Noncompetitive Receptor Antagonists and Ethanol in Inbred Long-Sleep and Short-Sleep Mice: Behavior and ElectrophysiologyALCOHOLISM, Issue 12 2000Taleen Hanania Background: Short-sleep (SS) mice exhibit higher locomotor activity than do long-sleep (LS) mice when injected with low doses of ethanol or the noncompetitive N -methyl-D-aspartate receptor (NMDAR) antagonist MK-801 (dizocilpine). SS mice also have higher densities of brain NMDARs. However, two strains of LS X SS recombinant inbred (RI) mice also show differential activation to ethanol and MK-801, but have similar numbers of NMDARs. Here we used inbred LS (ILS) and SS (ISS) mice to investigate further the relationship between NMDARs and sensitivity to the stimulant effects of low doses of ethanol. Methods: Open field activity and spontaneous alternations were measured after saline or drug injection. [3H]MK-801 binding parameters were determined in hippocampus, cortex, striatum, and nucleus accumbens. Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region of hippocampal slices. Results: Systemic injection of either ethanol or MK-801 increased locomotor activity to a greater extent in ISS mice than in ILS mice. The competitive NMDAR antagonist 2-carboxypiperazin-4-yl-propyl-1,1phosphonic acid (±CPP) depressed activity of ILS, but not ISS, mice. No strain differences were observed in spontaneous alternations or in the number or affinity of NMDARs in the brain regions examined. Likewise, the magnitudes of hippocampal NMDAR-mediated fEPSPs were similar in ILS and ISS mice and were inhibited to the same extent by a competitive NMDAR antagonist. However, both ethanol and the NMDAR NR2B receptor antagonist ifenprodil inhibited the late component of hippocampal NMDAR fEPSPs to a greater extent in ISS, than in ILS, mice. Conclusions: Differential ethanol- and MK-801-induced behavioral activation in ILS and ISS mice was not associated with differences in NMDAR number. Nonetheless, pharmacological differences in hippocampal NMDAR responsiveness suggest that ISS mice express NMDARs that have a greater sensitivity to noncompetitive, but not competitive, NMDAR antagonists. These differences, which may reflect differences in NMDAR subunit composition, could underlie the differential responsiveness to low doses of ethanol in ILS and ISS mice. [source] Different Sensitivity to Ethanol in Alcohol-Preferring sP and -Nonpreferring sNP RatsALCOHOLISM, Issue 11 2000Giancarlo Colombo Background and Objectives Clinical research has proposed that initial sensitivity to ethanol may be negatively correlated with levels of subsequent ethanol intake; consistently, alcohol-preferring P rats were found to be less sensitive to the ataxic and sedative/hypnotic effects of ethanol than -nonpreferring NP rats. The present study investigated the initial sensitivity to the ataxic and sedative/hypnotic effects of ethanol and to the sedative/hypnotic effects of pentobarbital and diazepam in selectively bred Sardinian alcohol-preferring sP and -nonpreferring sNP rats. Methods: In experiment 1, time to lose (onset) and regain (sleep time) the righting reflex after the acute intraperitoneal (ip) administration of 3.0 and 3.5 g/kg ethanol were measured in sP and sNP rats. In experiment 2, sP and sNP rats were required to perform a motor coordination task on a Rota-Rod after the acute intragastric administration of 2.0, 2.5, and 3.0 g/kg ethanol. Experiment 3 assessed onset and sleep time in sP and sNP rats after the acute injection of pentobarbital (40 mg/kg; ip) and diazepam (15 and 20 mg/kg; ip). Results: In experiment 1, sP rats took shorter times to lose the righting reflex and regained this reflex over longer periods of time and at lower blood ethanol levels than sNP rats. In experiment 2, ethanol affected motor coordination to a greater extent in sP than sNP rats. In contrast, results from experiment 3 showed that sP and sNP rats were not differentially sensitive to the sedative/hypnotic effects of pentobarbital and diazepam. Conclusions: The results of experiments 1 and 2 suggest that sP rats possess a genetically determined, greater sensitivity to the motor impairing and sedative/hypnotic effects of ethanol than sNP rats. Although caution should be adopted before hypothesizing any comparison to humans, these results may feature sP rats as an experimental model of those subsets of human alcoholics with initial high sensitivity to ethanol challenges. Finally, the results of experiment 3 suggest a minimal involvement of the benzodiazepine and barbiturate recognition sites in the differential sensitivity to ethanol of sP and sNP rats. [source] Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian ShepherdJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005J. GEYER A subpopulation of dogs of the Collie and Australian Shepherd breeds show increased sensitivity to central nervous actions of ivermectin, doramectin, loperamide, and probably several other drugs. The molecular background for this greater sensitivity is a nonsense mutation in the MDR1 efflux pump, which is part of the functional blood,brain barrier and normally limits drug penetration into the brain. This report describes a rapid PCR-based method for detection of this nt230(del4) MDR1 mutation using a small amount of genomic DNA from blood cells. Thereby, homozygous intact, homozygous mutated, and heterozygous mutated MDR1 genotypes can be clearly differentiated by high resolution polyacrylamide gel electrophoresis. Using this diagnostic test two Collies and one Australian Shepherd were screened for the nt230(del4) MDR1 mutation. The Collies had no history of altered drug sensitivity and showed homozygous intact and heterozygous mutated MDR1 alleles, respectively. However, the Australian Shepherd developed clear signs of neurotoxicity including ataxia, crawling, acoustic and tactile hyperexcitability, and miosis after a single dose of moxidectin (400 ,g/kg). For this dog two mutated MDR1 alleles were detected. This report describes for the first time moxidectin neurotoxicosis in a dog with a homozygous MDR1 mutation. [source] The use of unsymmetrical indirect covariance NMR methods to obtain the equivalent of HSQC-NOESY dataMAGNETIC RESONANCE IN CHEMISTRY, Issue 7 2007Kirill A. Blinov We have recently demonstrated that unsymmetrical indirect covariance NMR methods can be used to mathematically calculate the equivalent of low sensitivity, hyphenated NMR experiments by combining data from a pair of higher sensitivity experiments. The present report demonstrates the application of this method to the combination of HSQC and NOESY spectra to provide results comparable to HSQC-NOESY data, albeit with greater sensitivity and with considerably less spectrometer time. Copyright © 2007 John Wiley & Sons, Ltd. [source] Temperature dependencies of amide 1H- and 15N-chemical shifts in hyaluronan oligosaccharidesMAGNETIC RESONANCE IN CHEMISTRY, Issue 5 2007Charles D. Blundell Abstract Temperature coefficients (,,/,T) of amide chemical shifts of N -acetylglucosamine residues have been measured in a range of oligosaccharides of the important vertebrate polysaccharide hyaluronan. Odd- and even-numbered oligosaccharides with glucuronic acid, ,-4,5-unsaturated glucuronic acid and N -acetylglucosamine at the termini were investigated. All amide proton temperature coefficients were only slightly less negative (,6.9 to , 9.1 ppb/ °C) than those of amide protons in free exchange with water (,, 11 ppb/ °C), indicating an absence of persistent intramolecular hydrogen bonds. With the exception of amide groups in reducing-terminal N -acetylglucosamine rings, all amide proton environments have the same temperature coefficient (,6.9 ppb/ °C), irrespective of differences in amide group chemical shifts and 3JHH coupling constants, i.e. they do not sense subtle differences in orientation of the amide group. Amide nitrogen temperature coefficients report the same phenomena but with greater sensitivity. These data provide a set of reference values for temperature coefficients measured in other carbohydrates with acetamido sugars. Copyright © 2007 John Wiley & Sons, Ltd. [source] Gender differences in drug effects: implications for anesthesiologistsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2003H. Pleym Background:, The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research. Methods:, Basis for this paper was obtained by Medline searches using the key words ,human' and ,gender' or ,sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies. Results:, Females have 20,30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30,40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30,40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males. Conclusion:, These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia. [source] Hexose-specificity of hexokinase and ADP-dependence of pyruvate kinase play important roles in the control of monosaccharide utilization in freshly diluted boar spermatozoaMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2006Antonio Medrano Abstract Incubation of boar sperm from fresh ejaculates in a minimal medium with 10 mM glucose induced a fast and intense activation of glycolysis, as indicated by the observed increases in the intracellular levels of glucose 6-phosphate (G 6-P) and ATP and the rate of formation of extracellular L -lactate. The effect of glucose was much more intense than that induced by fructose, sorbitol, and mannose. The greater utilization of glucose was related to a much greater sensitivity to hexokinase when compared with the other monosaccharides. Thus, the presence of 0.5 mM glucose induced total hexokinase activity in supernatants from sperm extracts of 1.7,±,0.1 mIU/mg protein, while the same concentration of both fructose, mannose, and sorbitol induced total hexokinase activity from 0.3,±,0.1 mIU/mg protein to 0.60,±,1 mIU/mg protein. Kinetic analysis of the total pyruvate kinase activity indicated that this activity was greatly dependent on the presence of ADP and also showed a great affinity for PEP, with an estimated Km in supernatants of 0.15,0.20 mM. Immunological location of proteins closely related to glycolysis, like GLUT-3 hexose transporter and hexokinase-I, indicated that these proteins showed the trend to be distributed around or in the cellular membranes of both head and midpiece in a grouped manner. We conclude that glycolysis is regulated by both the specific availability of a concrete sugar and the internal equilibrium between ATP and ADP levels. Furthermore, localization of proteins involved in the control of monosaccharide uptake and phosphorylation suggests that glycolysis starts at concrete points in the boar-sperm surface. Mol. Reprod. Dev. 1179,1194, 2006. © 2006 Wiley-Liss, Inc. [source] New developments of brain imaging for Parkinson's disease and related disorders,MOVEMENT DISORDERS, Issue 12 2006Paola Piccini MD Abstract Parkinson's disease (PD) and related disorders are subcortical degenerations targeting the nigrostriatal dopaminergic system and basal ganglia. Traditionally, MRI has been used to detect structural and positron emission tomography and single emission computed tomography functional neurochemical and metabolic changes associated with these disorders. Recently, advances in diffusion-weighted MRI, ultrasonography, and radiotracer-based imaging have yielded greater sensitivity for revealing structural change and allowed detection of changes in brain dopamine levels after levodopa and during behavioral tasks. This review focuses on these recent advances in neuroimaging technology and their use for the diagnosis and assessment of PD and other parkinsonian disorders. © 2006 Movement Disorder Society [source] When to use the combined sensory index,MUSCLE AND NERVE, Issue 8 2001Matthew P. Kaul MD Abstract A recently developed electrodiagnostic technique, the combined sensory index (CSI), has been recommended for its greater sensitivity in diagnosing carpal tunnel syndrome (CTS). The CSI requires a greater number of procedures and therefore involves greater time, cost, and patient discomfort than does conventional electrodiagnostic testing. The CSI is composed of three commonly used electrodiagnostic techniques. There is a close correlation between the components of the CSI, and in most cases, all three components of the CSI are in agreement. We performed a study to develop and validate an algorithm that could be used to identify subsets of patients with CTS in whom CSI testing is particularly useful. Subjects were consecutive outpatient veterans referred by a heterogeneous group of specialists and generalists for electrodiagnostic evaluation of paresthesias in a median distribution with nocturnal exacerbation of symptoms. The CSI served as our gold standard. Using our simple algorithm, we found that in approximately 95% of cases, it was unnecessary to perform the CSI. This management strategy improves patient comfort and reduces electrodiagnostic cost while identifying the minority of patients for whom the CSI is indicated. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1078,1082, 2001 [source] | |||||||||||||||||||||||||||||||||||||