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Discernible Effect (discernible + effect)
Selected AbstractsShareholder Income Taxes and the Relation between Earnings and Returns,CONTEMPORARY ACCOUNTING RESEARCH, Issue 3 2005DAN S. DHALIWAL Abstract The purpose of this study is to investigate whether and how shareholder-level taxes affect earnings response coefficients (ERCs). Our tests indicate that when the tax rate on dividends increases, ERCs decrease for firms with high levels of dividend yield and whose marginal investor is likely to be an individual. For firms with high levels of share repurchase yield and whose marginal investor is likely to be an individual, an increase in dividend tax rate has no discernible effect on ERCs. These results are consistent with the notion that the tax penalty on dividends, relative to capital gains, reduces the earnings-return relation. [source] Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjectsDIABETIC MEDICINE, Issue 10 2010C. Ellero Diabet. Med. 27, 1168,1173 (2010) Abstract Aims, Transient nausea and, to a lesser extent, vomiting are common adverse effects of exenatide that can be mitigated by dose titration and usually do not result in treatment discontinuation. This retrospective analysis of data from a phase 1, open-label, parallel-group, single-dose study in healthy subjects evaluated the effect of oral anti-emetics on exenatide-associated nausea and vomiting and on the pharmacokinetics of exenatide. Methods, A single subcutaneous dose (10 ,g) of exenatide was administered to 120 healthy subjects (19,65 years, BMI 23,35 kg/m2). Incidences of nausea and vomiting were compared between 60 subjects premedicated with two oral anti-emetics 30 min before the exenatide dose and 60 non-premedicated subjects. Similarly, the area under the concentration-time curve (AUC) and the maximum observed concentration (Cmax) of plasma exenatide concentrations over 8 h post-dose were compared. Results, Among all subjects [61% male, 32 ± 12 years, body mass index (BMI) 29.1 ± 3.4 kg/m2 (mean ± sd)], mild to moderate nausea was the most frequent adverse event after exenatide dosing. Vomiting was also observed. Subjects premedicated with anti-emetics experienced significantly less nausea and vomiting (16.7 and 6.7%, respectively) vs. non-premedicated subjects (61.7 and 38.3%, respectively; P -value < 0.0001 for both nausea and vomiting). The mean area under the concentration-time curve and the maximum observed concentration AUC and Cmax of plasma exenatide concentrations during 8 h post-dose were not significantly different between groups. Conclusion, Administration of oral anti-emetics before a single 10-,g exenatide dose was associated with significant reductions in treatment-emergent nausea and vomiting, with no discernible effect on the pharmacokinetics of exenatide. Use of anti-emetic therapy may provide a short-term strategy to minimize the nausea and vomiting associated with exenatide treatment. [source] Misfolded transthyretin causes behavioral changes in a Drosophila model for transthyretin-associated amyloidosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Malgorzata Pokrzywa Abstract Familial amyloidotic polyneuropathy is an autosomal dominant neurodegenerative disorder caused by accumulation of mutated transthyretin (TTR) amyloid fibrils in different organs and prevalently around peripheral nerves. We have constructed transgenic flies, expressing the clinical amyloidogenic variant TTRL55P and the engineered variant TTR-A (TTRV14N/V16E) as well as the wild-type protein, all in secreted form. Within a few weeks, both mutants but not the wild-type TTR demonstrated a time-dependent aggregation of misfolded molecules. This was associated with neurodegeneration, change in wing posture, attenuation of locomotor activity including compromised flying ability and shortened life span. In contrast, expression of wild-type TTR had no discernible effect on either longevity or behavior. These results suggest that Drosophila can be used as a disease-model to study TTR amyloid formation, and to screen for pharmacological agents and modifying genes. [source] The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and inhibitor selectivityFEBS JOURNAL, Issue 6 2001Vera Knäuper Interstitial collagen is degraded by members of the matrix metalloproteinase (MMP) family, including MMP-1. Previous work has shown that the region of MMP-1 coded for by exon 5 is implicated both in substrate specificity and inhibitor selectivity. We have constructed a chimeric enzyme, the exon 5 chimera, consisting primarily of MMP-1, with the region coded for by exon 5 replaced with the equivalent region of MMP-3, a noncollagenolytic MMP. Unlike MMP-3, the exon 5 chimera is capable of cleaving type I collagen, but the activity is only 2.2% of trypsin-activated MMP-1. ,Superactivation' of the chimera has no discernible effect, suggesting that the salt bridge formed in ,superactive' MMP-1 is not present. The kinetics for exon 5 chimera cleavage of two synthetic substrates display an MMP-3 phenotype, however, cleavage of gelatin is slightly impaired as compared to the parent enzymes. The Kiapp values for the exon 5 chimera complexed with synthetic inhibitors and N-terminal TIMP-2 also show a more MMP-3-like behaviour. However, the kon values for N-terminal TIMP-1 and N-terminal TIMP-2 are more comparable to those for MMP-1. These data show that the region of MMP-1 coded for by exon 5 is involved in both substrate specificity and inhibitor selectivity and the structural basis for our findings is discussed. [source] Stream temperature and the potential growth and survival of juvenile Oncorhynchus mykiss in a southern California creekFRESHWATER BIOLOGY, Issue 7 2007DAVID A. BOUGHTON Summary 1.,We asked whether an increase in food supply in the field would increase the ability of fish populations to withstand climate warming, as predicted by certain bioenergetic models and aquarium experiments. 2.,We subsidised the in situ food supply of wild juvenile steelhead (Oncorhynchus mykiss) in a small stream near the species' southern limit. High-quality food (10% of fish biomass per day) was added to the drift in eight in-stream enclosures along a naturally-occurring thermal gradient. 3.,The temperatures during the experiment were well below the upper thermal limit for the species (means of enclosures ranged from 15.1 to 16.5 °C). Food supplements had no discernible effect on survival, but raised mean (± SD) specific growth rate substantially, from 0.038 ± 0.135 in controls to 2.28 ± 0.51 in feeding treatments. Food supplements doubled the variation in growth among fish. 4.,The mean and variance of water temperature were correlated across the enclosures, and were therefore transformed into principal component scores T1 (which expressed the stream-wide correlation pattern) and T2 (which expressed local departures from the pattern). Even though T1 accounted for 96% of the variation in temperature mean and variance, it was not a significant predictor of fish growth. T2 was a significant predictor of growth. The predicted time to double body mass in an enclosure with a large T2 score (cool-variable) was half that in an enclosure with a low T2 score (warm-stable). 5.,Contrary to expectation, temperature effects were neutral, at least with respect to the main axis of variation among enclosures (cool-stable versus warm-variable). Along the orthogonal axis (cool-variable versus warm-stable), the effect was opposite from expectations, probably because of temperature variation. Subtle patterns of temperature heterogeneity in streams can be important to potential growth of O. mykiss. [source] A self-restrained approach to nation-building by foreign powersINTERNATIONAL AFFAIRS, Issue 1 2004Amitai Etzioni Nation-building by foreign powers can rarely be accomplished and tends to be very costly, not merely in economic resources and those of political capital, but also in human lives. Foreign powers often attempt to tackle numerous tasks with little discernible effect. Therefore, whatever resources foreign powers are willing and able to commit should be focused on a modest agenda,what is termed in this article a ,restrained approach,. A restrained approach focuses first and foremost on pacification and security, it deals with whoever is in power initially and it requires local people to overcome some challenges by themselves. Greatly curtailing foreign ambitions and promises will lead to much greater credibility of drives for democratization; will provide stronger domestic support for such efforts among the taxpayers and donors who have to foot the bills; and will pay off by focusing more resources on the few facets of society that are relatively easy to change. [source] Sleep-disordered breathing in a general heart failure population: relationships to neurohumoral activation and subjective symptomsJOURNAL OF SLEEP RESEARCH, Issue 1 2006ARCHANA RAO Summary The aim of this study was to determine the prevalence of sleep-related breathing disorders (SDB) in a UK general heart failure (HF) population, and assess its impact on neurohumoral markers and symptoms of sleepiness and quality of life. Eighty-four ambulatory patients (72 male, mean (SD) age 68.6 (10) yrs) attending UK HF clinics underwent an overnight recording of respiratory impedance, SaO2 and heart rate using a portable monitor (Nexan). Brain natriuretic peptide (BNP) and urinary catecholamines were measured. Subjective sleepiness and the impairment in quality of life were assessed (Epworth Sleepiness Scale (ESS), SF-36 Health Performance Score). SDB was classified using the Apnoea/Hypopnoea Index (AHI). The prevalence of SDB (AHI > 15 events h,1) was 24%, increasing from 15% in mild-to-moderate HF to 39% in severe HF. Patients with SDB had significantly higher levels of BNP and noradrenaline than those without SDB (mean (SD) BNP: 187 (119) versus 73 (98) pg mL,1, P = 0.02; noradrenaline: 309 (183) versus 225 (148) nmol/24 h, P = 0.05). There was no significant difference in reported sleepiness or in any domain of SF-36, between groups with and without SDB (ESS: 7.8 (4.7) versus 7.5 (3.6), P = 0.87). In summary, in a general HF clinic population, the prevalence of SDB increased with the severity of HF. Patients with SDB had higher activation of a neurohumoral marker and more severe HF. Unlike obstructive sleep apnoea, SDB in HF had little discernible effect on sleepiness or quality of life as measured by standard subjective scales. [source] Evidence that WbpD is an N -acetyltransferase belonging to the hexapeptide acyltransferase superfamily and an important protein for O-antigen biosynthesis in Pseudomonas aeruginosa PAO1MOLECULAR MICROBIOLOGY, Issue 5 2005Cory Q. Wenzel Summary Di- N -acetylated uronic acid residues are unique sugar moieties observed in the lipopolysaccharides (LPS) of respiratory pathogens including several serotypes of Pseudomonas aeruginosa and several species of Bordetella. WbpD of P. aeruginosa PAO1 (serotype O5) is a putative 3- N -acetyltransferase that has been implicated in the biosynthesis of UDP-2,3-diacetamido-2,3-dideoxy- d -mannuronic acid [UDP- d -Man(2NAc3NAc)A], a precursor for the d -Man(2NAc3NAc)A residues in the B-band O antigen of this bacterium. A chromosomal knockout mutant of wbpD is incapable of producing either long-chain B-band O antigen (, 2 repeating units) or semi-rough LPS (lipid A-core + one repeat). Adding wbpD in trans restored LPS production to the wild-type level; this indicates that wbpD is important for biosynthesis of individual B-band O-antigen repeating units. WbpD contains left-handed beta-helical (L,H) structure as observed by Conserved Domain analysis and in silico secondary and tertiary structure predictions. This feature suggested that WbpD belongs to the hexapeptide acyltransferase (HexAT) superfamily of enzymes. WbpD was overexpressed as an N-terminally histidine-tagged fusion protein (His6,WbpD) and purified to >,95% purity. The protein was subjected to Far-UV circular dichroism spectroscopy, and the data revealed that WbpD contains left-handed helical structure, which substantiated in silico predictions made earlier. Results from SDS-PAGE, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS), and gel filtration analyses indicated that His6 -WbpD has trimeric organization, consistent with the quaternary structure of HexATs. The binding of acetyl-CoA by WbpD was demonstrated by MALDI-TOF MS, suggesting that WbpD is an acetyltransferase that utilizes a direct-transfer reaction mechanism. Incubation of WbpD with acetyl-CoA significantly enhanced the stability of the protein and prevented precipitation over a course of 14 days. As a substrate for studying the enzymatic activity of WbpD is unavailable at present, a structure-based model for the L,H domain of WbpD was generated. Comparisons between this model and the L,H domains of known HexATs suggested that Lys136 plays a role in acetyl-CoA binding. A K136A site-directed mutant construct could only partially complement the wbpD knockout, and this mutation also reduced the stabilizing effects of acetyl-CoA, while a K136R mutation showed no discernible effect on complementation of the wbpD mutant or the stabilizing effects of acetyl-CoA on the purified mutant protein. A modified pathway was proposed for the biosynthesis of UDP- d -Man(2NAc3NAc)A, in which WbpD is involved in the catalysis of the fourth step by acting as a UDP-2-acetamido-3-amino-2,3-dideoxy- d -glucuronic acid 3- N -acetyltransferase. [source] Capsaicin delays regeneration of the neuromuscular junction of rat extensor digitorum longus muscle after ischemiaMUSCLE AND NERVE, Issue 4 2006Béla Turchányi MD Abstract Trauma or the tourniquet used in orthopedic surgery is often associated with ischemia,reperfusion (I/R) injury with a consequent decrease of muscle power. To explore whether components of the neuromuscular junction (NMJ) are involved in this muscle dysfunction, NMJs were ultrastructurally characterized in the extensor digitorum longus muscle of rats at reperfusion times of 1, 24, 72, and 168 h after a 120-min arterial occlusion. Disorganization of the presynaptic membrane and mitochondrial injury was noted at 1 h, followed by fragmentation and partial engulfment of nerve terminals by Schwann cells at 24 and 72 h. The magnitude of degenerative changes declined at 168 h, suggesting the commencement of regeneration. The postsynaptic membrane remained intact throughout the whole period. In our previous study, deafferentation with pretreatment of the sciatic nerve with capsaicin, which reduces neurogenic inflammation and has a selective effect on nociceptive fibers, improved functional recovery of the muscle after I/R. The present results document a significantly delayed structural regeneration of the motor nerve terminals after combined capsaicin and I/R treatment. Since capsaicin treatment alone had no discernible effect on the structure of NMJs, the findings point to a possibly indirect effect of capsaicin on the motor nerves, which may predispose them to increased susceptibility unmasked only by a subsequent injury. The mismatch between the enhanced functional improvement of the muscle and delayed regeneration of the nerve after capsaicin pretreatment questions the efficient use of such deafferentation to protect the integrity of neuromuscular junctions in I/R injury. Muscle Nerve, 2006 [source] UNDERSTANDING REACTIONS TO JOB REDESIGN: A QUASI-EXPERIMENTAL INVESTIGATION OF THE MODERATING EFFECTS OF ORGANIZATIONAL CONTEXT ON PERCEPTIONS OF PERFORMANCE BEHAVIORPERSONNEL PSYCHOLOGY, Issue 2 2006FREDERICK P. MORGESON Redesigning jobs from a traditional workgroup structure to a semi-autonomous team structure has become increasingly popular, but the impact of such redesigns on employee effectiveness criteria has been mixed. The present longitudinal quasi-experimental study showed that although such a redesign had positive effects on 3 performance behaviors (effort, skill usage, and problem solving), its effectiveness also depended on aspects of the organizational context. In conditions where the organizational reward and feedback and information systems were effective, redesigning work into a semi-autonomous team structure had no discernible effect on performance behaviors. In conditions where these systems were poor, however, such a redesign produced large positive benefits. This suggests that work redesigns that enhance worker autonomy are most effective in contexts where other supportive management systems are absent. [source] Virucidal activity of essential oils from aromatic plants of San Luis, ArgentinaPHYTOTHERAPY RESEARCH, Issue 9 2003C. C. García Abstract Essential oils obtained from eight aromatic plants of San Luis Province, Argentina, were screened for virucidal activity against herpes simplex virus type 1 (HSV-1), Junin virus (JUNV) and dengue virus type 2 (DEN-2). The most potent inhibition was observed with the essential oil of Lippia junelliana and Lippia turbinata against JUNV with virucidal concentration 50% (VC50) values in the range 14,20 ppm, whereas Aloysia gratissima, Heterotheca latifolia and Tessaria absinthioides inhibited JUNV in the range 52,90 ppm. The virucidal activity was time- and temperature-dependent. The essential oils of A. gratissima, Artemisia douglasiana, Eupatorium patens and T. absinthioides inactivated HSV-1 at 65,125 ppm. However, only A. douglasiana and E. patens had any discernible effect on DEN-2 infectivity with VC50 values of 60 and 150 ppm, respectively. Copyright © 2003 John Wiley & Sons, Ltd. [source] Selective over-expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2007K Sahadevan Abstract Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1,4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over-expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1,3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over-expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over-expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Evaluation of fungal antagonists for grey mould management in early growth of pot rosesANNALS OF APPLIED BIOLOGY, Issue 1 2004D S YOHALEM Summary Several filamentous fungi can reduce disease incidence and suppress sporulation of Botrytis cinerea during early establishment and vegetative growth of pot roses. Two isolates of Ulocladium atrum were the most successful of those fungi tested, were consistently more effective than the fungicide, iprodione and not different from each other. Tween 80, added as a dispersant, had no effect on the efficacy of U. atrum. An isolate of Clonostachys rosea also gave better disease control than iprodione, although not to the levels given by isolates of U. atrum, nor was its behaviour consistent across experiments. Another isolate of C. rosea performed well in one trial, had no discernible effect in a second and was excluded from the third due to poor inoculum quality. Commercial Trichoderma harzianum preparations (Trichodex and Supresivit) failed to reduce disease incidence under the high disease pressure of these experiments, but did reduce sporulation of the pathogen relative to untreated controls. [source] | |||||||||||||