Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “double robustness”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1987

Behavioral determination of refractory periods of the brainstem substrates of self-stimulation.

The objective of this study was to estimate the refractory periods of the brainstem neurons responsible for self-stimulation behavior in the rat. In a first experiment, we tested the robustness of the double pulse technique used to estimate the refractory periods of reward-relevant neurons. We obtained estimates of the relative T-pulse effectiveness at a wide range of stimulation frequencies. The results of this experiment suggest that the refractory period estimates obtained with the behavioral version of the double pulse technique are not dependent on the arbitrary choice of the stimulation frequency. However, the use of stimulation frequencies higher than 100 Hz should preferably be avoided. In a second experiment, we applied the double pulse technique using C-pulse intensity higher than T-pulse intensity to estimate the refractory periods of the brainstem reward-relevant neurons. Using moveable electrodes, we tested 9 metencephalic and 7 mesencephalic sites in 4 animals. In the metencephalon, the most excitable reward-relevant neurons have absolute refractory periods of less than 0.6 and 0.8 ms and have a supernormal period that occurs at least between 5 and 10 ms after the initial excitation. The mesencephalic reward-relevant neurons were found to have more heterogeneous physiological characteristics. The most excitable cells in the mesencephalon have absolute refractory periods of less than 0.4 ms and have a supernormal period occurring as soon as 2.4 ms after the initial excitation. At some mesencephalic sites, we observed first an abrupt initial recovery followed by a plateau, followed by a renewed and continuous recovery, a pattern that was never observed in the metencephalon. The hypothesis of the contribution of two distinct sub-populations of reward-relevant neurons is proposed and the implication of monoaminergic pathways in reward is discussed.

Animals↗
PubMed2005

Hiding anxiety versus acknowledgment of anxiety in social interaction: relationship with social anxiety.

According to cognitive and interpersonal models, safety behaviors in social phobia (e.g., avoiding eye contact, hiding blushing) erroneously induce negative evaluation by interaction partners. Presumably, a bias about the social outcome of safety behaviors causes this negative interaction cycle. Such a bias might be subject to double standard in social phobia (i.e., having more stringent rules for oneself than for others). Female students (n=81) predicted more negative social outcomes for a prominent type of safety behavior, hiding anxiety, than for the opposite behavior, acknowledgment of anxiety and ongoing behavior (control condition) in scripts of self- and other-target persons. The relation between social anxiety and double standard was robust. Social anxiety did not relate to a cognitive bias regarding hiding ones anxiety, as we expected, but was associated with the belief that acknowledgment of anxiety has negative social outcomes specifically for them. These results are evaluated in light of the interpersonal consequences anxiety-related behaviors have in social interactions.

Adolescent↗
PubMed1999

Diurnal modulation of long-term potentiation in the hamster hippocampal slice.

Long-term potentiation (LTP) was examined in hippocampal slices from Syrian hamsters entrained to a LD 14:10 cycle. Population spike (PS) amplitudes from CA1 pyramidal cells were measured before (control) and after tetanizing the Schaffer/collateral commissural pathway. Slices from animals sacrificed during the day, between zeitgeber time (ZT) 0430 and 0530, were incubated, and then tetanized between ZT 1340 and 1930, where ZT=0 denotes lights on. Slices from animals sacrificed during the night, between ZT 1830 and 1930, were incubated, and tetanized between ZT 0030 and 0410. LTP, a sustained increase in PS amplitude following tetanus, was evoked in both groups. PS amplitude increased by 102.7+/-20.3% in animals sacrificed during the day and by 48.0+/-7.5% in animals sacrificed during the night (p<0.05). Thus hamster slices prepared during the day show more robust LTP (a doubling of PS amplitude), a difference persisting in slices incubated for several hours.

Animals↗
PubMed1998

Polyunsaturated membranes are required for photosynthetic competence in a mutant of Arabidopsis.

High levels of polyunsaturation are characteristic of all the membranes of plant and animal cells. For example, the chloroplasts of leaf cells contain about 75-80% polyunsaturated fatty acids. For the extra-chloroplast membranes in leaf cells and the membranes of non-photosynthetic tissues, values of 60-65% are typical. We report here the production of Arabidopsis double mutants that contain negligible levels of polyunsaturated fatty acids. The mutants were not capable of autotrophic growth and produced extremely chlorotic cotyledons and leaves. However, on sucrose media, the double mutants were robust plants showing strong leaf and root development. These observations indicate that the vast majority of receptor-mediated and transport-related membrane functions required to sustain the organism and induce proper development are adequately supported in the absence of polyunsaturated lipids. By contrast, photosynthesis is one process that does require high levels of membrane polyunsaturation.

Arabidopsis↗
PubMed2002

The RecA intein of Mycobacterium tuberculosis promotes cleavage of ectopic DNA sites. Implications for the dispersal of inteins in natural populations.

The RecA intein of Mycobacterium tuberculosis, a novel double-stranded DNA endonuclease, requires both Mn(2+) and ATP for efficient cleavage of the inteinless recA allele. In this study, we show that Mg(2+) alone was sufficient to stimulate PI-MtuI to cleave double-stranded DNA at ectopic sites. In the absence of Mg(2+), PI-MtuI formed complexes with topologically different forms of DNA containing ectopic recognition sequences with equal affinity but failed to cleave DNA. We observed that PI-MtuI was able to inflict double-strand breaks robustly within the ectopic recognition sequence to generate either a blunt end or 1-2-nucleotide 3'-hydroxyl overhangs. Mutational analyses of the presumptive metal ion-binding ligands (Asp(122), Asp(222), and Glu(220)) together with immunoprecipitation assays provided compelling evidence to link both the Mg(2+)- and Mn(2+) and ATP-dependent endonuclease activities to PI-MtuI. The kinetic mechanism of PI-MtuI promoted cleavage of ectopic DNA sites proceeded through a sequential mechanism with transient accumulation of nicked circular duplex DNA as an intermediate. Together, these data suggest that PI-MtuI, like group II introns, might mediate ectopic DNA transposition and hence its lateral transfer in natural populations.

Adenosine Triphosphate↗
PubMed1998

Cdc1 and the vacuole coordinately regulate Mn2+ homeostasis in the yeast Saccharomyces cerevisiae.

The yeast CDC1 gene encodes an essential protein that has been implicated in the regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the Cdc1-dependent process, we isolated second-site suppressors of the conditional cdc1-1(Ts) growth defect. Recessive suppressors define 15 COS (CdcOne Suppressor) genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole, an organelle known to sequester intracellular Mn2+. An eighth gene, COS16, encodes a vacuolar membrane protein that seems to be involved in Mn2+ homeostasis. These results suggest mutations that block vacuolar Mn2+ sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is dispensable in a cos16delta deletion strain, and a cdc1delta cos16delta double mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn2+.

ADP-Ribosylation Factors↗
PubMed2005

Robust visualization of the dental occlusion by a double scan procedure.

A detailed visualization of the dental occlusion in 3D image-based planning environments for oral and maxillofacial planning is important. With CT imaging however, this occlusion is often deteriorated by streak artifacts caused by amalgam fillings. Moreover, more detailed surface information at the level of the dental cuspids is often desired. In this paper, a double scan technique is introduced to image the dental occlusion by means of a newly designed 3D splint. The patient wears this splint between the upper and lower teeth during CT-scan. In a second step, the splint is positioned between the plaster casts of the upper and lower jaw, and this setup is scanned. Based on markers in the 3D splint, both data sets are fused and a combined visualization is possible. The accuracy, robustness and applicability in clinical routine is shown. This technology enables meticulous 3D cephalometric analysis, detailed maxillofacial planning and opens possibilities towards intraoperative support.

Cadaver↗
PubMed2006

Theory and applications of supercycled symmetry-based recoupling sequences in solid-state nuclear magnetic resonance.

We present the theoretical principles of supercycled symmetry-based recoupling sequences in solid-state magic-angle-spinning NMR. We discuss the construction procedure of the SR26 pulse sequence, which is a particularly robust sequence for double-quantum homonuclear dipole-dipole recoupling. The supercycle removes destructive higher-order average Hamiltonian terms and renders the sequence robust over long time intervals. We demonstrate applications of the SR26 sequence to double-quantum spectroscopy, homonuclear spin counting, and determination of the relative orientations of chemical shift anisotropy tensors.

Journal Article↗
PubMed2002

A structural double-mutant cycle: estimating the strength of a buried salt bridge in barnase.

Double-mutant cycles are widely used in the field of protein engineering to measure intermolecular and intramolecular interactions. Ideally, there should be no structural rearrangement of the protein on making the two single mutations and the double mutation within the cycle. However, structural pertubation on mutation does not preclude the use of this method, providing the sum of the changes in the single mutants equals the change in the double mutant. In this way, the energy associated with any structural rearrangement cancels in the double-mutant cycle. Previously, the contribution of a buried salt bridge between Arg69 and Asp93 in barnase to the stability of the folded protein has been determined by double-mutant cycle analysis. In order to determine whether the measured interaction of -14.0 kJ mol(-1) represents the true interaction energy, the crystal structure of each mutant within the double-mutant cycle was solved. Although mutation results in structural shifts, the majority of those in the single mutants are also found in the double mutant; their energetic effects in the double-mutant cycle are therefore cancelled. This study highlights the robust nature of the double-mutant cycle analysis.

Arginine↗
PubMed2002

Alteration of cortical EEG in mice carrying mutated human APP transgene.

Transgenic mice expressing human APPswe and PS1-A264E mutations mimic certain neuropathological features of Alzheimer's disease (AD). These mice have elevated levels of the highly fibrillogenic amyloid beta1-42 peptide (Abeta42) and develop amyloid plaques around the age of 9 months. Our aim was to find whether these transgenic mice differ electrophysiologically from non-transgenic mice and whether the alteration in EEG activity progresses with the accumulation of Abeta. The APP/PS1 mice had reduced cortical theta activity and enhanced beta and gamma activity, but these changes were not age-dependent. APP single mutant mice had similar EEG alterations in theta, beta and gamma bands as APP/PS1 double mutant mice while PS1 single mutant mice did not differ from non-transgenic controls. Insoluble Abeta40 and Abeta42 levels were robustly increased in APP/PS1 double mutant mice and insoluble Abeta40 moderately increased also in APP single mutant mice. Soluble Abeta42 was found in all APP mutant mice but also in lower concentrations in PS1 single mutant mice. Plaques were deposited in 13-month-old APP/PS1 double mutant mice but not in 8-month-old double mutant or 13-month-old single mutant mice. We conclude that the alteration of EEG activity in APP/PS1 double mutant and APP single mutant mice is related to their APP genotype rather than to deposition of beta-amyloid in the brain.

Action Potentials↗
PubMed1999

Laminar-selective noradrenergic and serotoninergic modulation includes spinoparabrachial cells after inflammation.

We evaluated the effects of chemical lesions on hindpaw inflammation-induced Fos protein expression in spinoparabrachial neurons that were retrogradely labeled by Fluoro-Gold. The descending serotoninergic and noradrenergic pathways were destroyed by the selective neurotoxins, 5,7-DHT and DSP-4, respectively. After 5,7-DHT treatment there was a significant increase in double-labeled neurons only in the lateral reticulated neck of the dorsal horn 24h after inflammation compared with vehicle-injected controls. In contrast, the DSP-4 treatment resulted in a more robust increase in double-labeled neurons in the ipsilateral superficial dorsal horn than in the neck of the dorsal horn. These results indicate that after inflammation the enhanced modulation from descending serotoninergic and noradrenergic pathways targets supraspinally projecting neurons to dampen increased ascending nociceptive input. Further, these pathways differentially suppress the responses of spinoparabrachial neurons in the deep and superficial dorsal horn.

5,7-Dihydroxytryptamine↗
PubMed2003

Reactivity at the beta-diketiminate ligand Nacnac- on titanium(IV) (Nacnac- = [Ar]NC(CH3)CHC(CH3)N[Ar], Ar = 2,6-[CH(CH3)2]2C6H3). Diimine-alkoxo and bis-anilido ligands stemming from the Nacnac- skeleton.

The reaction of ketene OCCPh(2) with the four-coordinate titanium(IV) imide (L(1))Ti[double bond]NAr(OTf) (L(1)(-) = [Ar]NC(CH(3))CHC(CH(3))N[Ar], Ar = 2,6-[CH(CH(3))(2)](2)C(6)H(3)) affords the tripodal dimine-alkoxo complex (L(2))Ti[double bond]NAr(OTf) (L(2)(-) = [Ar]NC(CH(3))CHC(O)[double bond]CPh(2)C(CH(3))N[Ar]). Complex (L(2))Ti[double bond]NAr(OTf) forms from electrophilic attack of the beta-carbon of the ketene on the gamma-carbon of the Nacnac(-) NCC(gamma)CN ring. On the contrary, nucleophiles such as LiR (R(-) = Me, CH(2)(t)Bu, and CH(2)SiMe(3)) deprotonate cleanly in OEt(2) the methyl group of the beta-carbon on the former Nacnac(-) backbone to yield the etherate complex (L(3))Ti[double bond]NAr(OEt(2)), a complex that is now supported by a chelate bis-anilido ligand (L(3)(2)(-) = [Ar]NC(CH(3))CHC(CH(2))N[Ar]). In the absence of electrophiles or nucleophiles, the robust (L(1))Ti[double bond]NAr(OTf) template was found to form simple adducts with Lewis bases such as CN(t)Bu or NCCH(2)(2,4,6-Me(3)C(6)H(2)). Complexes (L(2))Ti[double bond]NAr(OTf), (L(3))Ti[double bond]NAr(OEt(2)), and the adducts (L(1))Ti[double bond]NAr(OTf)(XY) [XY = CN(t)Bu and NCCH(2)(2,4,6-Me(3)C(6)H(2))] were structurally characterized by single-crystal X-ray diffraction studies.

Journal Article↗
PubMed2005

Arterial macrophages and regenerating endothelial cells express P-selectin in atherosclerosis-prone apolipoprotein E-deficient mice.

P-selectin expression has been reported in platelets, endothelial cells, and vascular smooth muscle cells in response to vascular injury. Here, we report P-selectin expression on macrophages in the arterial wall after carotid denudation injury and spontaneous atherosclerosis in atherosclerosis-prone apoE-deficient (apoE(-/-)) mice. Double-immunofluorescence staining revealed robust P-selectin expression in macrophage-rich regions of both denudation-induced carotid neointimal lesions and innominate atherosclerotic plaques. Co-localization of P-selectin with macrophages was verified at the single cell level using double immunostaining plus 4,6-diamidino-2-phenylindole (for nuclei) counterstaining. No platelet staining was seen in association with the macrophage staining, excluding platelet contamination. Furthermore, P-selectin mRNA expression was readily detectable in macrophage-rich plaques of atherosclerotic innominate arteries and blood monocyte-derived macrophages from apoE(-/-) mice. Strong P-selectin expression was also seen in the areas of regenerated endothelium after arterial injury. In addition, co-localization of P-selectin with vascular smooth muscle cells was readily observed in denudation-injured carotid arteries at 7 and 14 days. We conclude that macrophages in carotid injury-induced neointimal lesions and spontaneous atherosclerotic plaques of the innominate artery acquire the ability to express P-selectin, as does regenerating endothelium. These findings provide a potential new paradigm in macrophage-mediated vascular inflammation, atherosclerosis, and neointimal hyperplasia after arterial injury.

Animals↗
PubMed1997

In vivo detection of GABA in human brain using a localized double-quantum filter technique.

A proton MR spectral editing technique employing a spatially localized, double-quantum filter (DQF) was used to measure gamma-aminobutyric acid (GABA) in the human brain at 1.5 T. The double-quantum method provided robust, single-shot suppression of uncoupled resonances from choline, creatine, and NAA and allowed detection of the gamma CH2 GABA (3.0 ppm) resonance with 30% efficiency. Spatial localization of the GABA measurement was achieved by incorporating PRESS localization within the double-quantum excitation and detection sequence. A calibration technique was developed to adjust the relative phases of the RF pulses to maximize the in vivo double-quantum detection efficiency for an arbitrary voxel location. The sequence efficiency, degree of suppression of uncoupled reasonances, and characterization of the in vivo DQF technique was examined in phantom experiments and in a study of the occipital lobe of 10 normal subjects. The ratio of the 3.0-ppm GABA resonance to the 3.0-ppm creatine resonance was found to be 0.20 +/- 0.05 (SD).

Brain Chemistry↗
PubMed2000

Circadian rhythms in Neurospora crassa: lipid deficiencies restore robust rhythmicity to null frequency and white-collar mutants.

The conidiation rhythm in the fungus Neurospora crassa is a model system for investigating the genetics of circadian clocks. Null mutants at the frq (frequency) locus (frq(9) and frq(10)) make no functional frq gene products and are arrhythmic under standard conditions. The white-collar strains (wc-1 and wc-2) are insensitive to most effects of light, and are also arrhythmic. All three genes are proposed to be central components of the circadian oscillator. We have been investigating two mutants, cel (chain-elongation) and chol-1 (choline-requirer), which are defective in lipid synthesis and affect the period and temperature compensation of the rhythm. We have constructed the double mutant strains chol-1 frq(9), chol-1 frq(10), chol-1 wc-1, chol-1 wc-2, cel frq(9), cel frq(10), and cel wc-2. We find that these double mutant strains are robustly rhythmic when assayed under lipid-deficient conditions, indicating that free-running rhythmicity does not require the frq, wc-1, or wc-2 gene products. The rhythms in the double mutant strains are similar to the cel and chol-1 parents, except that they are less sensitive to light. This suggests that the frq, wc-1, and wc-2 gene products may be components of a pathway that normally supplies input to a core oscillator to transduce light signals and sustain rhythmicity. This pathway can be bypassed when lipid metabolism is altered.

Cell Division↗
PubMed1982

A human-hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia-derived line.

A rapidly-growing, HAT-sensitive cell line LICR-LON-HMy2 has been derived from the ARH-77 human plasma cell leukemia-derived line. It lacks the enzyme hypoxanthine phosphoribosyltransferase (EC 2.4.2.8). Hybrids have been reproducibly made for more than a year and in independent laboratories with lymphocytes from tonsils, lymph nodes and peripheral blood and tonsil lymphocytes cultured with antigens. The parent line and hybrids are very robust in culture and double in 20-30 h. Hybrids clone easily and have stable karyotypes, most with modal numbers in the sixties. Stable Ig secretion patterns have been observed over 20-30 passages, and after cloning. It was estimated that about half the hybrids produce new immunoglobulin chains in addition to the parent cell line's IgG1 (kappa light chain). High, but not limiting, density hybridoma cultures (approximately 5 x 10(5) cells/ml) typically produce 0.25-2 micrograms/ml immunoglobulin per day, but some hybrids produce more. A high-secreting variant of LICR-LON-HMy2 has been derived. The LICR-LON-HMy2 line is human and is distinct from the HAT-sensitive human B cell-lines SKO-007 and GM 1500-6TG Al 2. It is available for distribution.

Antibodies, Monoclonal↗
PubMed2026

De novo transcriptome meta-analysis reveals candidate genes involved in life-stage transitions for RNAi-mediated management of the citrus root weevil (Diaprepes abbreviatus).

BACKGROUND: The citrus root weevil, Diaprepes abbreviatus, is a destructive agricultural pest for which molecular control options remain limited due to historically sparse genomic resources. Leveraging a comprehensive de novo transcriptome, we investigated developmental gene regulation across larval, pupal, and adult stages and identified essential targets for RNA interference (RNAi)-based intervention. RESULTS: Stage-resolved transcriptomic analyses revealed extensive transcriptional reprogramming associated with metabolism, detoxification, cuticle biosynthesis, endocrine signaling, and sensory perception. Among these, chitin synthase (DaCHS) emerged as a critical developmental gene, exhibiting pronounced up-regulation during late larval and pupal stages corresponding to intensive cuticle synthesis. Phylogenetic and structural analyses demonstrated that DaCHS is highly conserved among insects and retains canonical catalytic domains and transmembrane topology. Alpha Fold-based structural modeling and molecular docking confirmed stable interaction of DaCHS with its substrate, N-acetylglucosamine, supporting functional conservation of enzymatic activity. Oral delivery of DaCHS double-stranded RNA induced robust transcript suppression, leading to significant mortality and severe developmental defects, including larval and pupal abnormalities, and adults with disrupted wing and abdominal morphogenesis. CONCLUSION: These findings establish DaCHS as an indispensable gene for D. abbreviates development and validate transcriptome-guided RNAi as a powerful framework for target discovery. This work provides a strong molecular foundation for developing RNAi-based strategies that can be integrated into sustainable management programs for citrus root weevil control. &#xa9; 2026 Society of Chemical Industry.

Animals↗