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Subtle Effects (subtle + effects)
Selected AbstractsFine-Tuning the Dimerization of Tetraureacalix[4]arenesCHEMISTRY - A EUROPEAN JOURNAL, Issue 15 2010Yuliya Rudzevich Dr. Abstract Calix[4]arenes substituted by four urea residues at their wide rim form hydrogen-bonded homo- and heterodimeric capsules in apolar solvents. If urea groups are covalently connected to loops or substituted by bulky residues, the dimerization may be restricted to those pairs in which the loops do not overlap and for which the residues are small enough to pass the loops. In the present study, we describe the dimerization properties of tetraureas with one, two (adjacent or opposite), three, or four loops and those bearing (additionally) up to four residues of different size: a=tolyl, b=3,5-di- tert -butylphenyl, c=4-propyloxy-3,5-di-(tert -butylphenyl)phenyl, and d=4-[tris-(4- tert -butylphenyl)methyl]phenyl. For compounds with four loops of different size (O(CH2)nO-chains with n=10, 14, and 20 connecting the m -positions of the urea phenyl residues) a clear "stepwise" sorting scheme could be established, in which the bulkiest residue d is excluded by all tetraloop compounds and the smallest residue a can pass only the smallest loops (n=10). The medium-sized residues b or c are tolerated by n=14 and 20 or only by n=20. Selectivities can be built up also on geometrical factors. A trisloop compound, for instance, combines only with a tetraurea bearing a single bulky residue and tetraureas with two bulky substituents in adjacent or opposite position are distinguished by the bisloop derivatives with adjacent or opposite loops. The impossibility to form a homodimer of a monoloop compound containing two bulky residues leads to its selective heterodimerization with a derivative bearing three bulky groups. Subtle effects for "borderline" cases, in which the dimerization or reorganization takes a longer time, are also discussed. [source] Responses of Tuatara (Sphenodon punctatus) to Removal of Introduced Pacific Rats from IslandsCONSERVATION BIOLOGY, Issue 4 2007DAVID R. TOWNS erradicación de rata del Pacífico; especie invasora; índice de condición corporal; tuatara Abstract:,Invasive mammalian predators such as rats are now widespread on islands, but hypotheses about their effects have rarely been tested. Circumstantial evidence from New Zealand indicates that, when introduced to islands, Pacific rats (Rattus exulans) have negative effects on endemic plants, invertebrates, birds, and reptiles, including the tuatara (Sphenodon punctatus). We tested the effects of Pacific rats on tuatara by comparing the demographic structure and body condition of tuatara populations on three islands before and after removal of rats and on a fourth island where rats remained. In the presence of rats, juvenile tuatara constituted on average 0,5% of the sample tuatara populations. When Pacific rats were removed after at least 200 years' occupancy, the proportion of juvenile tuatara increased 3.5- to 17-fold and body condition of adult males and females also improved (sometimes dramatically). We predict that, unless Pacific rats are removed from Taranga Island, the tuatara population will collapse because of low population density and the lack of juvenile recruitment. Our results demonstrate that when invasive species exert subtle effects on recruitment and body condition, the effects on populations of long-lived endemic species may only become apparent long after the invasion. Resumen:,Actualmente, los depredadores mamíferos invasores, como las ratas, están ampliamente extendidos en islas, pero las hipótesis sobre sus efectos han sido probadas pocas veces. Evidencia circunstancial de Nueva Zelanda indica que, cuando son introducidas a islas, las ratas del Pacífico (Rattus exulans) tienen un efecto negativo sobre plantas, invertebrados, aves y reptiles endémicos, incluyendo el tuatara (Sphenodon punctatus). Probamos los efectos de ratas del Pacífico sobre tuatara mediante la comparación de la estructura demográfica y la condición corporal de poblaciones de tuatara en tres islas antes y después de la remoción de ratas y en una cuarta isla donde permanecían las ratas. En la presencia de ratas, tuatara juveniles constituían, en promedio, 0,5% de las poblaciones de tuatara. Cuando las ratas eran removidas después de por lo menos 200 años de ocupación, la proporción de tuatara juveniles incremento entre 3.5 y 17 veces y la condición corporal de los machos y hembras adultas también mejoró (algunas veces dramáticamente). Pronosticamos que, a menos que las ratas del Pacífico sean removidas de la Isla Taranga, las poblaciones de tuatara se colapsarán debido a una densidad poblacional baja y por la ausencia de reclutamiento de juveniles. Nuestros resultados demuestran que cuando las especies invasoras ejercen efectos sutiles sobre el reclutamiento y la condición corporal, los efectos sobre las poblaciones de especies endémicas longevas se vuelven aparentes mucho tiempo después de la invasión. [source] Acute effects of desmin mutations on cytoskeletal and cellular integrity in cardiac myocytesCYTOSKELETON, Issue 2 2003Kurt Haubold Mutations in desmin have been associated with a subset of human myopathies. Symptoms typically appear in the second to third decades of life, but in the most severe cases can manifest themselves earlier. How desmin mutations lead to aberrant muscle function, however, remains poorly defined. We created a series of four mutations in rat desmin and tested their in vitro filament assembly properties. RDM-G, a chimera between desmin and green fluorescent protein, formed protofilament-like structures in vitro. RDM-1 and RDM-2 blocked in vitro assembly at the unit-length filament stage, while RDM-3 had more subtle effects on assembly. When expressed in cultured rat neonatal cardiac myocytes via adenovirus infection, these mutant proteins disrupted the endogenous desmin filament to an extent that correlated with their defects in in vitro assembly properties. Disruption of the desmin network by RDM-1 was also associated with disruption of plectin, myosin, and ,-actinin organization in a significant percentage of infected cells. In contrast, expression of RDM-2, which is similar to previously characterized human mutant desmins, took longer to disrupt desmin and plectin organization and had no significant effect on myosin or ,-actinin organization over the 5-day time course of our studies. RDM-3 had the mildest effect on in vitro assembly and no discernable effect on either desmin, plectin, myosin, or ,-actinin organization in vivo. These results indicate that mutations in desmin have both direct and indirect effects on the cytoarchitecture of cardiac myocytes. Cell Motil. Cytoskeleton 54:105,121, 2003. © 2003 Wiley-Liss, Inc. [source] Arrested differentiation and epithelial cell degeneration in zebrafish lens mutantsDEVELOPMENTAL DYNAMICS, Issue 4 2001Thomas S. Vihtelic Abstract In a chemical mutagenesis screen, we identified two zebrafish mutants that possessed small pupils. Genetic complementation revealed these two lines are due to mutations in different genes. The phenotypes of the two mutants were characterized using histologic, immunohistochemical, and tissue transplantation techniques. The arrested lens (arl) mutant exhibits a small eye and pupil phenotype at 48 hr postfertilization (hpf) and lacks any histologically identifiable lens structures by 5 days postfertilization (dpf). In contrast, the disrupted lens (dsl) mutants are phenotypically normal until 5 dpf, and then undergo lens disorganization and cell degeneration that is apparent by 7 dpf. Histology reveals the arl mutant terminates lens cell differentiation by 48 hpf, whereas the dsl lens exhibits a defective lens epithelial cell population at 5 dpf. Lens transplantation experiments demonstrate both mutations are autonomous to the lens tissue. Immunohistochemistry reveals the retinal cells may suffer subtle effects, possibly due to the lens abnormalities. © 2001 Wiley-Liss, Inc. [source] Genetic variants of insulin receptor substrate-1 (IRS-1) in syndromes of severe insulin resistance.DIABETIC MEDICINE, Issue 10 2002Functional analysis of Ala513Pro, Gly1158Glu IRS- Abstract Aims To define further the role of IRS-1 mutations in human syndromes of severe insulin resistance. Methods The IRS-1 gene was scanned for mutations in 83 unrelated affected subjects and 47 unaffected individuals using fluorescent single-strand conformation polymorphism (fSSCP) analysis. A novel heterozygous mutation, Gly1158Glu, was found in one affected subject. Four and two subjects were heterozygous for the previously reported variants Gly972Arg and Ala513Pro, respectively. The previously identified variant Gly819Arg was found in one affected and one unaffected subject. While Gly972Arg has been described to alter the signalling properties of IRS-1, no functional studies of Ala513Pro or Gly1158Glu have been reported. Results Chinese hamster ovary (CHO) cells stably over-expressing the insulin receptor were transiently transfected with vectors expressing either wild-type, Glu1158 or Pro513 IRS-1. A modest increase in insulin-stimulated tyrosine phosphorylation of Glu1158 IRS-1 was observed. However, this did not result in any significant change in the association of Grb2 or the p85, subunit of PI3-kinase or of PI3-kinase activity. In parallel studies, the Pro513 IRS-1 variant was indistinguishable from wild-type IRS-1. Conclusions While subtle effects of these variants cannot be excluded in this system, it is unlikely that these variants are responsible for the extreme insulin resistance seen in the subjects harbouring them. Although IRS proteins play a central role in insulin signalling, functionally significant mutations in the IRS-1 gene are a rare cause of human syndromes of severe insulin resistance. [source] A test of the community conditioning hypothesis: Persistence of effects in model ecological structures dosed with the jet fuel jp-8ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Wayne G. Landis Abstract The foundation of the community conditioning hypothesis, the persistence of effects, was tested in a series of microcosm experiments. Experiments were conducted with the water-soluble fraction of the turbine fuel JP-8 using the standard protocols for the standardized aquatic microcosm (SAM). A repeat trial was conducted using the SAM protocol but with a 126-d test period, twice the standard duration. The results were examined using a variety of conventional univariate, multivariate, and graphical techniques. The principal conclusions were as follows. Effects are persistent in these model ecological systems long after the degradation of the toxicant. Patterns of impacts are detectable at concentrations 15 times lower than an experimentally derived single-species EC50. The replicate experiments are not replicable in the specific, but the broad pattern of the disruption of algal- herbivore dynamics followed by more subtle effects are consistently repeated. The durability of the indirect effects and therefore the information about historical events appears to be a consistent feature of these microcosm systems. The identity of the treatment groups persists. The critical features of the community conditioning hypothesis,persistence of information within ecologicalsystems and the reappearance of patterns and therefore the nonequilibrium dynamics,are again confirmed. The implications of these findings for environmental toxicology, monitoring, and ecological risk assessment are discussed. [source] Cerebral Damage in Epilepsy: A Population-based Longitudinal Quantitative MRI StudyEPILEPSIA, Issue 9 2005Rebecca S. N. Liu Summary:,Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community-based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. Methods: One hundred seventy-nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures. [source] GFAP: Functional implications gleaned from studies of genetically engineered miceGLIA, Issue 1 2003Albee Messing Abstract GFAP is the major intermediate filament of mature astrocytes, and its relatively specific expression in these cells suggests an important function. To study the role of the GFAP gene, mice have been created carrying null alleles (no protein), modified alleles (altered protein), or added wild type alleles (elevated protein). Surprisingly, absence of GFAP has relatively subtle effects on development. On the other hand, over-expression can be lethal, and led to the discovery that GFAP coding mutations are responsible for most cases of Alexander disease, a devastating neurodegenerative disorder. Here we review what the various GFAP mouse models reveal about GFAP and astrocyte function. GLIA 43:87,90, 2003. © 2003 Wiley-Liss, Inc. [source] Factors Associated with the Income Distribution of Full-Time Physicians: A Quantile Regression ApproachHEALTH SERVICES RESEARCH, Issue 5 2007Ya-Chen Tina Shih Objective. Physician income is generally high, but quite variable; hence, physicians have divergent perspectives regarding health policy initiatives and market reforms that could affect their incomes. We investigated factors underlying the distribution of income within the physician population. Data Sources. Full-time physicians (N=10,777) from the restricted version of the 1996,1997 Community Tracking Study Physician Survey (CTS-PS), 1996 Area Resource File, and 1996 health maintenance organization penetration data. Study Design. We conducted separate analyses for primary care physicians (PCPs) and specialists. We employed least square and quantile regression models to examine factors associated with physician incomes at the mean and at various points of the income distribution, respectively. We accounted for the complex survey design for the CTS-PS data using appropriate weighted procedures and explored endogeneity using an instrumental variables method. Principal Findings. We detected widespread and subtle effects of many variables on physician incomes at different points (10th, 25th, 75th, and 90th percentiles) in the distribution that were undetected when employing regression estimations focusing on only the means or medians. Our findings show that the effects of managed care penetration are demonstrable at the mean of specialist incomes, but are more pronounced at higher levels. Conversely, a gender gap in earnings occurs at all levels of income of both PCPs and specialists, but is more pronounced at lower income levels. Conclusions. The quantile regression technique offers an analytical tool to evaluate policy effects beyond the means. A longitudinal application of this approach may enable health policy makers to identify winners and losers among segments of the physician workforce and assess how market dynamics and health policy initiatives affect the overall physician income distribution over various time intervals. [source] Structural MRI biomarkers for preclinical and mild Alzheimer's disease,HUMAN BRAIN MAPPING, Issue 10 2009Christine Fennema-Notestine Abstract Noninvasive MRI biomarkers for Alzheimer's disease (AD) may enable earlier clinical diagnosis and the monitoring of therapeutic effectiveness. To assess potential neuroimaging biomarkers, the Alzheimer's Disease Neuroimaging Initiative is following normal controls (NC) and individuals with mild cognitive impairment (MCI) or AD. We applied high-throughput image analyses procedures to these data to demonstrate the feasibility of detecting subtle structural changes in prodromal AD. Raw DICOM scans (139 NC, 175 MCI, and 84 AD) were downloaded for analysis. Volumetric segmentation and cortical surface reconstruction produced continuous cortical surface maps and region-of-interest (ROI) measures. The MCI cohort was subdivided into single- (SMCI) and multiple-domain MCI (MMCI) based on neuropsychological performance. Repeated measures analyses of covariance were used to examine group and hemispheric effects while controlling for age, sex, and, for volumetric measures, intracranial vault. ROI analyses showed group differences for ventricular, temporal, posterior and rostral anterior cingulate, posterior parietal, and frontal regions. SMCI and NC differed within temporal, rostral posterior cingulate, inferior parietal, precuneus, and caudal midfrontal regions. With MMCI and AD, greater differences were evident in these regions and additional frontal and retrosplenial cortices; evidence for non-AD pathology in MMCI also was suggested. Mesial temporal right-dominant asymmetries were evident and did not interact with diagnosis. Our findings demonstrate that high-throughput methods provide numerous measures to detect subtle effects of prodromal AD, suggesting early and later stages of the preclinical state in this cross-sectional sample. These methods will enable a more complete longitudinal characterization and allow us to identify changes that are predictive of conversion to AD. Hum Brain Mapp 2009. © 2009 Wiley-Liss, Inc. [source] Community assemblage patterns of odonates inhabiting a wetland complex influenced by anthropogenic disturbanceINSECT CONSERVATION AND DIVERSITY, Issue 2 2009BRYAN A. REECE Abstract., 1Many wetland complexes around the world are highly influenced by human activity (chiefly land conversion for agriculture). Measuring the impact of such activity hinges not only upon using appropriate wetland indicator taxa but also upon metrics that are sensitive enough to capture subtle effects. 2Over a 5-year period, we quantified the distribution and community structure of odonates (dragonflies and damselflies) occupying a wetland complex in Texas. When using traditional community metrics, there were no significant differences in diversity or evenness in the odonate assemblages in wetlands surrounded by the two dominant regional forms of land use (tilled cropland and grassland). Similarity analyses likewise failed to detect any significant differences in odonate community composition with land use. 3Discriminant function analysis, however, revealed that species co-occurrences could be distinguished on the basis of surrounding land use, which indicates that odonate assemblages in these wetlands are structured in a manner that typical community metrics fail to adequately describe. 4Differences between the approaches are discussed, particularly with regard to the use of presence,absence data. [source] Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteriaJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2003S.E. Walsh Abstract Aims: This study investigates the antimicrobial activity and mode of action of two natural products, eugenol and thymol, a commonly utilized biostatic agent, triclocarban (TCC), and two surfactants, didecyldimethylammonium chloride (DDDMAC) and C10,C16 alkyldimethyl amine N -oxides (ADMAO). Methods and Results: Methods used included: determination of minimum inhibitory concentrations (MICs), lethal effect studies with suspension tests and the investigation of sub-MIC concentrations on growth of E. coli, Staph. aureus and Ps. aeruginosa using a Bioscreen microbiological analyser. Leakage of intracellular constituents and the effects of potentiating agents were also investigated. Only DDDMAC was bactericidal against all of the organisms tested. Eugenol, thymol and ADMAO showed bacteriostatic and bactericidal activity, but not against Ps. aeruginosa. TCC was only bacteristatic against Staph. aureus, but like the other agents, it did affect the growth of the other organisms in the Bioscreen experiments. All of the antimicrobial agents tested were potentiated by the permeabilizers to some extent and leakage of potassium was seen with all of the agents except TCC. Conclusions: DDDMAC was bactericidal against all organisms tested and all compounds had some bacteriostatic action. Low level static effects on bacterial growth were seen with sub-MIC concentrations. Membrane damage may account for at least part of the mode of action of thymol, eugenol, DDDMAC and ADMAO. Significance and Impact of the Study: The ingredients evaluated demonstrated a range of bactericidal and bacteriostatic properties against the Gram-negative and -positive organisms evaluated and the membrane (leakage of intracellular components) was implicated in the mode of action for most (except TCC). Sub-MIC levels of all ingredients did induce subtle effects on the organisms which impacted bacterial growth, even for those which had no true inhibitory effects. [source] Electric field-derived point charges to mimic the electrostatics in molecular crystalsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 10 2006Andrew E. Whitten Abstract Because of the way the electrostatic potential is defined in a crystal, it is not possible to determine potential-derived charges for atoms in a crystal. To overcome this limitation, we present a novel method for determining atomic charges for a molecule in a crystal based on a fit to the electric field at points on a surface around the molecule. Examples of fits to the electric field at points on a Hirshfeld surface, using crystal Hartree,Fock electron densities computed with a DZP basis set are presented for several organic molecular crystals. The field-derived charges for common functional groups are transferable, and reflect chemical functionality as well as the subtle effects of intermolecular interactions. The charges also yield an excellent approximation to the electric field surrounding a molecule in a crystal for use in cluster calculations on molecules in solids. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1063,1070, 2006 [source] Comparative Response to a Survey Executed by Post, E-mail, & Web FormJOURNAL OF COMPUTER-MEDIATED COMMUNICATION, Issue 1 2000Gi Woong Yun Recent developments in communication technologies have created alternative survey methods through e-mail and Web sites. Both methods use electronic text communication, require fewer resources, and provide faster responses than traditional paper and pencil methods. However, new survey methodologies also generate problems involving sampling, response consistency and participant motivation. Empirical studies need to be done to address these issues as researchers implement electronic survey methods. In this study we conduct an analysis of the characteristics of three survey response modes: post, e-mail, and Web site. Data are from a survey of the National Association of Science Writers (NASW), in which science writers' professional use of e-mail and the Web is evaluated. Our analysis offers two lessons. First, a caution. We detect a number of potentially important differences in the response characteristics of these three groups. Researchers using multi-mode survey techniques should keep in mind that subtle effects might be at play in their analyses. Second, an encouragement. We do not observe significant influences of survey mode in our substantive analyses. We feel, at least in this case, that the differences detected in the response groups indicate that using multi-mode survey techniques improved the representativeness of the sample without biasing other results. [source] Shuttle craft: a candidate quantitative trait gene for Drosophila lifespanAGING CELL, Issue 5 2004Elena G. Pasyukova Summary Variation in longevity in natural populations is attributable to the segregation of multiple interacting loci, whose effects are sensitive to the environment. Although there has been considerable recent progress towards understanding the environmental factors and genetic pathways that regulate lifespan, little is known about the genes causing naturally occurring variation in longevity. Previously, we used deficiency complementation mapping to map two closely linked quantitative trait loci (QTL) causing female-specific variation in longevity between the Oregon (Ore) and 2b strains of Drosophila melanogaster to 35B9,C3 and 35C3 on the second chromosome. The 35B9,C3 QTL encompasses a 50-kb region including four genes, for one of which, shuttle craft (stc), mutations have been generated. The 35C3 QTL localizes to a 200-kb interval with 15 genes, including three genes for which mutations exist (reduced (rd), guftagu (gft) and ms(2)35Ci). Here, we report quantitative complementation tests to mutations at these four positional candidate genes, and show that ms(2)35Ci and stc are novel candidate quantitative trait genes affecting variation in Drosophila longevity. Complementation tests with stc alleles reveal sex- and allele-specific failure to complement, and complementation effects are dependent on the genetic background, indicating considerable epistasis for lifespan. In addition, a homozygous viable stc allele has a sex-specific effect on lifespan. stc encodes an RNA polymerase II transcription factor, and is an attractive candidate gene for the regulation of longevity and variation in longevity, because it is required for motoneuron development and is expressed throughout development. Quantitative genetic analysis of naturally occurring variants with subtle effects on lifespan can identify novel candidate genes and pathways important in the regulation of longevity. [source] Multiple Roles for the Endocannabinoid System During the Earliest Stages of Life: Pre- and Postnatal DevelopmentJOURNAL OF NEUROENDOCRINOLOGY, Issue 2008E. Fride The endocannabinoid system, including its receptors (CB1 and CB2), endogenous ligands (,endocannabinoids'), synthesising and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. In addition, the endocannabinoids, notably 2-arachidonyl glycerol, are also present in maternal milk. During three distinct developmental stages (i.e. embryonic implantation, prenatal brain development and postnatal suckling), the endocannabinoid system appears to play an essential role for development and survival. Thus, during early pregnancy, successful embryonic passage through the oviduct and implantation into the uterus both require critical enzymatic control of optimal anandamide levels at the appropriate times and sites. During foetal life, the cannabinoid CB1 receptor plays a major role in brain development, regulating neural progenitor differentiation into neurones and glia and guiding axonal migration and synaptogenesis. Postnatally, CB1 receptor blockade interferes with the initiation of milk suckling in mouse pups, by inducing oral motor weakness, which exposes a critical role for CB1 receptors in the initiation of milk suckling by neonates, possibly by interfering with innervation of the tongue muscles. Manipulating the endocannabinoid system by pre- and/or postnatal administration of cannabinoids or maternal marijuana consumption, has significant, yet subtle effects on the offspring. Thus, alterations in the dopamine, GABA and endocannabioid systems have been reported while enhanced drug seeking behaviour and impaired executive (prefrontal cortical) function have also been observed. The relatively mild nature of the disruptive effects of prenatal cannabinoids may be understood in the framework of the intricate timing requirements and frequently biphasic effects of the (endo)cannabinoids. In conclusion, the endocannabinoid system plays several key roles in pre- and postnatal development. Future studies should further clarify the mechanisms involved and provide a better understanding of the adverse effects of prenatal exposure, in order to design strategies for the treatment of conditions such as infertility, mental retardation and failure-to-thrive. [source] Modeling l-dopa purification by chiral ligand-exchange chromatographyAICHE JOURNAL, Issue 3 2007Nooshafarin Sanaie Abstract A model describing elution-band profiles that combines multiple chemical equilibria theory with the nonideal equilibrium,dispersion equation for solute transport is used to predict and characterize the separation of l,d-dopa by chiral ligand-exchange chromatography (CLEC). Formation constants and stoichiometries for all equilibrium complexes formed in the interstitial volume and pore liquid are taken from standard thermodynamic databases and independent potentiometric titration experiments. Formation constants for complexes formed with the stationary phase ligand (N-octyl-3-octylthio-d-valine) are determined from potentiometric titration data for a water-soluble analogue of the ligand. This set of pure thermodynamic parameters is used to calculate the spatially discretized composition of each column volume element as a function of time. The model includes a temperature-dependent pure-component parameter, determined by regression to a single elution band for the pure component, that corrects for subtle effects associated with immobilizing the N-octyl-3-octylthio-d-valine ligand onto the stationary phase. The model is shown to accurately predict elution chromatograms and separation performance as a function of key column operating variables. The model is then used to better understand the connection between chemical equilibria within the system and changes in band profiles and band separation resulting from changes in column operating conditions. © 2007 American Institute of Chemical Engineers AIChE J, 2007 [source] Transport of neurofilaments in growing axons requires microtubules but not actin filamentsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005Franto Francis Abstract Neurofilament (NF) polymers are conveyed from cell body to axon tip by slow axonal transport, and disruption of this process is implicated in several neuronal pathologies. This movement occurs in both anterograde and retrograde directions and is characterized by relatively rapid but brief movements of neurofilaments, interrupted by prolonged pauses. The present studies combine pharmacologic treatments that target actin filaments or microtubules with imaging of NF polymer transport in living axons to examine the dependence of neurofilament transport on these cytoskeletal systems. The heavy NF subunit tagged with green fluorescent protein was expressed in cultured sympathetic neurons to visualize NF transport. Depletion of axonal actin filaments by treatment with 5 ,M latrunculin for 6 hr had no detectable effect on directionality or transport rate of NFs, but frequency of movement events was reduced from 1/3.1 min of imaging time to 1/4.9 min. Depolymerization of axonal microtubules using either 5 ,M vinblastine for 3 hr or 5 ,g/ml nocodazole for 4,6 hr profoundly suppressed neurofilament transport. In 92% of treated neurons, NF transport was undetected. These observations indicate that actin filaments are not required for neurofilament transport, although they may have subtle effects on neurofilament movements. In contrast, axonal transport of NFs requires microtubules, suggesting that anterograde and retrograde NF transport is powered by microtubule-based motors. © 2005 Wiley-Liss, Inc. [source] Prospective studies of exposure to an environmental contaminant: The challenge of hypothesis testing in a multivariate correlational contextPSYCHOLOGY IN THE SCHOOLS, Issue 6 2004Joseph L. Jacobson In this paper, we respond to the criticisms and concerns raised by D.V. Cicchetti, A.S. Kaufman, & S.S. Sparrow (this issue) in their review of the PCB literature, with particular attention to our own research in Michigan. We agree that multiple comparisons and functional significance are issues that would benefit from more discussion. However, because the effects associated with exposure to environmental contaminants are generally subtle, the risk of Type II error would be unacceptably high if researchers were to adopt the authors' recommendation to use a Bonferroni correction. We describe the hierarchical approach we have used to deal with the issue of multiple comparisons, which emphasizes the need to base interpretation on consistent patterns in the data and on replicated findings. The issue of confounding is one that has received considerable attention in the PCB studies and, given that one can never measure every possible confounder, the range of control variables that have been evaluated is impressive. We disagree with the authors' assertion that only standardized test scores are sufficiently reliable for use in these studies; behavioral teratogens often involve subtle effects, which can be identified most effectively by innovative, narrow-band tests that have not yet been normed. Moreover, longitudinal statistical analysis is not necessarily the method of choice for the issues being addressed in this literature. One important new development that Cicchetti et al. fail to note is the emergence of evidence from both the Michigan and Dutch cohorts indicating that breast-fed children are markedly less vulnerable. It is not yet clear to what degree this protective effect is attributable to nutrients in breast milk or to more optimal intellectual stimulation by nursing mothers, or both. However, the discovery of effect modifiers that can explain individual differences in vulnerability marks an important advance in our growing understanding of the teratogenic effects of exposure to environmental contaminants on child development. © 2004 Wiley Periodicals, Inc. Psychol Schs 41: 625,637, 2004. [source] | |||||||||||||||||||