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Selected AbstractsDeciphered Chemical Shifts in Aliased Spectra Recorded with two Slightly Different Narrow Windows or Differential Chemical Shift EvolutionCHEMPHYSCHEM, Issue 12 2010Mohammadali Foroozandeh The overlap of two HSQC spectra recorded with 10 and 9.9 ppm carbon spectral windows gives rise to highly resolved signals with a pattern providing unambiguous precise and accurate chemical shifts (see picture). Alternatively, the new DENA-HSQC pulse sequence takes advantage of a differential evolution of carbon chemical shift to do the same in a single experiment. Combined with multiplicity edition, DENA-HSQC advantageously replaces commonly used 1D DEPT-135 experiments. [source] Inventing paganism in eighth-century BavariaEARLY MEDIEVAL EUROPE, Issue 1 2010Jonathan Couser This article examines the hagiographies of Saints Emmeram and Corbinian and the synod of Neuching from eighth-century Bavaria. It argues that the references to pagan survivals in these texts are misleading, in the absence of other evidence of paganism in the region. Rather, since these texts were composed in a narrow window of time from 769,774, this anxiety reflects concerns aroused by pagan uprisings in neighbouring Carantania, which were only suppressed in 772. Thus, the texts' authors ,invented' paganism in their own culture as their perceptions of the dividing lines between Christianity and paganism grew sharper. [source] Body-wave traveltime and amplitude shifts from asymptotic travelling wave couplingGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 2 2006F. Pollitz SUMMARY We explore the sensitivity of finite-frequency body-wave traveltimes and amplitudes to perturbations in 3-D seismic velocity structure relative to a spherically symmetric model. Using the approach of coupled travelling wave theory, we consider the effect of a structural perturbation on an isolated portion of the seismogram. By convolving the spectrum of the differential seismogram with the spectrum of a narrow window taper, and using a Taylor's series expansion for wavenumber as a function of frequency on a mode dispersion branch, we derive semi-analytic expressions for the sensitivity kernels. Far-field effects of wave interactions with the free surface or internal discontinuities are implicitly included, as are wave conversions upon scattering. The kernels may be computed rapidly for the purpose of structural inversions. We give examples of traveltime sensitivity kernels for regional wave propagation at 1 Hz. For the direct SV wave in a simple crustal velocity model, they are generally complicated because of interfering waves generated by interactions with the free surface and the Mohorovi,i, discontinuity. A large part of the interference effects may be eliminated by restricting the travelling wave basis set to those waves within a certain range of horizontal phase velocity. [source] Strategies for identifying genes that play a role in spinal cord regenerationJOURNAL OF ANATOMY, Issue 1 2004M. Wintzer Abstract A search for genes that promote or block CNS regeneration requires numerous approaches; for example, tests can be made on individual candidate molecules. Here, however, we describe methods for comprehensive identification of genes up- and down-regulated in neurons that can and cannot regenerate after injury. One problem concerns identification of low-abundance genes out of the 30 000 or so genes expressed by neurons. Another difficulty is knowing whether a single gene or multiple genes are necessary. When microchips and subtractive differential display are used to identify genes turned on or off, the numbers are still too great to test which molecules are actually important for regeneration. Candidates are genes coding for trophic, inhibitory, receptor and extracellular matrix molecules, as well as unknown genes. A preparation useful for narrowing the search is the neonatal opossum. The spinal cord and optic nerve can regenerate after injury at 9 days but cannot at 12 days after birth. This narrow window allows genes responsible for the turning off of regeneration to be identified. As a next step, sites at which they are expressed (forebrain, midbrain, spinal cord, neurons or glia, intracellular or extracellular) must be determined. An essential step is to characterize proteins, their levels of expression, and their importance for regeneration. Comprehensive searches for molecular mechanisms represent a lengthy series of experiments that could help in devising strategies for repairing injured spinal cord. [source] A spatial model of coexistence among three Banksia species along a topographic gradient in fire-prone shrublandsJOURNAL OF ECOLOGY, Issue 5 2002J. Groeneveld Summary 1A spatially explicit, rule-based model for three co-occurring Banksia species was developed to investigate coexistence mediating processes in a fire-prone shrubland in western Australia. Fecundity, recruitment, mortality and other biological data for two non-sprouting (B. hookeriana, B. prionotes) and one resprouting (B. attenuata) species were available from 15 years of empirical field studies. 2Without interspecific competition, each species could persist for a wide range of fire intervals (10 to > 20 years). The resprouting species performed better under shorter fire intervals (10,13 years), while both non-sprouting species were favoured by longer (15 to > 20 years) fire intervals. These results conform with those obtained from single-species, non-spatial population models. 3When interspecific competition for space was included in the model, all three species exhibited optima at shorter fire intervals and with a narrower range than in isolation. The three species did not co-occur under any fire regime. At intermediate fire frequencies (11,13 years), B. hookeriana excluded the other species, while for longer intervals between fires B. prionotes became dominant. 4The introduction of temporal (stochastic) variability in fire intervals (drawn from a normal distribution) failed to produce coexistence, unless spatial variability as a spatial ignition gradient was also included. The spatial arrangement of the non-sprouters observed in the field was then reproduced. 5Observed patterns of coexistence and spatial distributions of all species occurred when a spatial establishment gradient for the resprouter species was included in the model (individuals of B. attenuata are known to produce more seeds in swales than on dune crests and recruit seedlings here more frequently). 6Coexistence appears to be highly dependent upon the mean interfire period in combination with subtle gradients associated with fire propagation and recruitment conditions. Variation around the mean fire interval is less critical. When the system is modelled over a long time period (1500 years) coexistence is most strongly favoured for a narrow window of mean fire intervals (12,14 years). [source] Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous systemJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Jian Feng Abstract To explore the role of DNA methylation in the brain, we examined the expression pattern of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the mouse central nervous system (CNS). By comparing the levels of Dnmt3a and Dnmt3b mRNAs and proteins in the CNS, we showed that Dnmt3b is detected within a narrow window during early neurogenesis, whereas Dnmt3a is present in both embryonic and postnatal CNS tissues. To determine the precise pattern of Dnmt3a and Dnmt3b gene expression, we carried out X-gal histochemistry in transgenic mice in which the lacZ marker gene is knocked into the endogenous Dnmt3a or Dnmt3b gene locus (Okano et al. [1999] Cell 99:247,257). In Dnmt3b - lacZ transgenic mice, X-gal-positive cells are dispersed across the ventricular zone of the CNS between embryonic days (E) 10.5 and 13.5 but become virtually undetectable in the CNS after E15.5. In Dnmt3a - lacZ mice, X-gal signal is initially observed primarily in neural precursor cells within the ventricular and subventricular zones between E10.5 and E17.5. However, from the newborn stage to adulthood, Dnmt3a X-gal signal was detected predominantly in postmitotic CNS neurons across all the regions examined, including olfactory bulb, cortex, hippocampus, striatum, and cerebellum. Furthermore, Dnmt3a signals in CNS neurons increase during the first 3 weeks of postnatal development and then decline to a relatively low level in adulthood, suggesting that Dnmt3a may be of critical importance for CNS maturation. Immunocytochemistry experiments confirmed that Dnmt3a protein is strongly expressed in neural precursor cells, postmitotic CNS neurons, and oligodendrocytes. In contrast, glial fibrillary acidic protein-positive astrocytes exhibit relatively weak or no Dnmt3a immunoreactivity in vitro and in vivo. Our data suggest that whereas Dnmt3b may be important for the early phase of neurogenesis, Dnmt3a likely plays a dual role in regulating neurogenesis prenatally and CNS maturation and function postnatally. © 2005 Wiley-Liss, Inc. [source] ,All-in-One' analysis for metabolite identification using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry with collision energy switchingRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2005Mark Wrona The removal of bottlenecks in discovery stage metabolite identification studies is an ongoing challenge for the pharmaceutical industry. We describe the use of an ,All-in-One' approach to metabolite characterization that leverages the fast scanning and high mass accuracy of hybrid quadrupole time-of-flight mass spectrometry (QqToFMS) instruments. Full-scan MS and MS/MS data is acquired using collision energy switching without the preselection, either manually or in a data-dependent manner, of precursor ions. The acquisition of ,clean' MS/MS data is assisted by the use of ultrahigh-performance chromatography. Data acquired using this method can then be mined post-acquisition in a number of ways. These include using narrow window extracted ion chromatograms (nwXICs) for expected biotransformations, XICs for the product ions of the parent compound and/or expected modification of these product ions, and neutral loss chromatograms. This approach has the potential to be truly comprehensive for the determination of in vitro biotransformations in a drug discovery environment. Copyright © 2005 John Wiley & Sons, Ltd. [source] Factors controlling the activity of the SERCA2a pump in the normal and failing heartBIOFACTORS, Issue 6 2009Ilse Vandecaetsbeek Abstract Heart failure is the leading cause of death in western countries and is often associated with impaired Ca2+ handling in the cardiomyocyte. In fact, cardiomyocyte relaxation and contraction are tightly controlled by the activity of the cardiac sarco(endo)plasmic reticulum (ER/SR) Ca2+ pump SERCA2a, pumping Ca2+ from the cytosol into the lumen of the ER/SR. This review addresses three important facets that control the SERCA2 activity in the heart. First, we focus on the alternative splicing of the SERCA2 messenger, which is strictly regulated in the developing heart. This splicing controls the formation of three SERCA2 splice variants with different enzymatic properties. Second, we will discuss the role and regulation of SERCA2a activity in the normal and failing heart. The two well-studied Ca2+ affinity modulators phospholamban and sarcolipin control the activity of SERCA2a within a narrow window. An aberrantly high or low Ca2+ affinity is often observed in and may even trigger cardiac failure. Correcting SERCA2a activity might therefore constitute a therapeutic approach to improve the contractility of the failing heart. Finally, we address the controversies and unanswered questions of other putative regulators of the cardiac Ca2+ pump, such as sarcalumenin, HRC, S100A1, Bcl-2, HAX-1, calreticulin, calnexin, ERp57, IRS-1, and ,2. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] Ventilation threshold as a measure of impaired physical performance in adults with growth hormone excessCLINICAL ENDOCRINOLOGY, Issue 3 2002Scott G. Thomas Summary objective Fatigue is a prominent symptom among patients with GH excess and acromegaly. Identifying the physiological basis of such complaints and obtaining objective measures to quantify their severity remains an ongoing challenge. We investigated whether submaximal measures of aerobic performance can be used to assess GH excess-associated fatigue objectively. design and patients To investigate this possibility we examined the relation between physical function and physical capacity in 12 patients with active acromegaly and persistent fatigue before and after 3 and 6 months of treatment with the long-acting somatostatin analogue octreotide (LAR®). measurements Heart rate (HR) and rating of perceived exertion (RPE using Borg's 10-point scale) were measured during a 160-metre self-paced walk test (SPW). Maximum oxygen uptake (VO2max) and ventilation threshold (VeT: a measure of work rate when breathlessness develops) were measured during a progressive treadmill test to fatigue or symptom-limited maximum. The Profile Of Mood States questionnaire (POMS) was used to quantify subjective feelings of fatigue and vigour. Morning fasting levels of GH and IGF-I were measured using immunoassay of serum samples. results SPW speed at a fast pace of 1·69 ± 0·18 m/s was achieved with higher than normal HR (112 ± 15/min; normal = 102) and RPE (2·4 ± 1·2). Similar to GH-deficient adults, VO2max (22·6 ± 6·4 ml.kg,1.min,1; normal ~30 ml.kg,1.min,1) and VeT (13·1 ± 2·9 ml.kg,1.min,1; predicted normal ~16 ml.kg,1(min,1) were low. However, VeT occurred at a normal fraction of VO2max (VeT/VO2max = 0·58). VeT was significantly increased and plasma IGF-I levels reduced following 3 and 6 months of octreotide LAR® treatment. Reduction in circulating IGF-I levels was correlated with improvement in reported vigour (r = 0·85) and VeT (r = 0·65) (P < 0·05). conclusions Our findings demonstrate impairment in physical function and physical capacity consistent with the perception of increased fatigue among acromegalic patients. These objective measures of compromised physical function are similar to the changes that we have reported previously in adults with GH deficiency. Taken together, these data suggest that a narrow window for GH/IGF-I levels is required to maintain optimal physical function. [source] | |||||||||||||