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PubMed1994

Postcranial robusticity in Homo. II: Humeral bilateral asymmetry and bone plasticity.

The analysis of humeral asymmetry in Recent human skeletal samples and an extant tennis-player sample documents minimal asymmetry in bone length, little asymmetry in distal humeral articular breadth, but pronounced and variable asymmetry in mid- and distal diaphyseal cross-sectional geometric parameters. More specifically, skeletal samples of normal modern Euroamericans, prehistoric and early historic Amerindians, and prehistoric Japanese show moderate (ca. 5-14%) median asymmetry in diaphyseal cross-sectional areas and polar second moments of area, whereas the tennis-player sample, with pronounced unilateral physical activity, exhibits median asymmetries of 28-57% in the same parameters. A sample of Neandertals with nonpathological upper limbs exhibits similarly low articular asymmetry but pronounced diaphyseal asymmetries, averaging 24-57%. In addition, three Neandertals with actual or possible post-traumatic upper limb alterations have the same low articular asymmetry but extremely high diaphyseal asymmetries, averaging 112-215%. These data support those from experimental work on animals, exercise programs of humans, and human clinical contexts in establishing the high degree of diaphyseal plasticity possible for humans, past and present, under changing biomechanical loading conditions. This lends support to activity-related functional interpretations of changing human diaphyseal morphology and robusticity during the Pleistocene.

Animals↗
PubMed1984

The effects of simulated increases in body weight for 30 and 60 days on bone robusticity of limb bones in rats.

The purpose of this study was to subject groups of weanling male rats each to a specific 10% simulated increase in body weight, ranging from 1.1G-2.0G, using constant centrifugation. (In this paper, "G" is the acceleration due to gravity.) After 30 and 60 days, rats were killed and perfused with 10% buffered neutral formalin (B.N.F.). The humerus, radius, ulna, femur, and tibia were removed, cleared of all soft tissues, weighed, and the total length measured. Bone robusticity was calculated using the ponderal index: bone length/3 square root bone weight. Tukey's Multiple Range Test was used. The data suggest that the specific limb bone, G, and duration of centrifugation are each factors in the response of limb bones to simulated increases in body weight.

Animals↗
PubMed2006

Gene profiling of scleroderma skin reveals robust signatures of disease that are imperfectly reflected in the transcript profiles of explanted fibroblasts.

OBJECTIVE: To determine whether biopsy specimens obtained from systemic sclerosis (SSc) lesions show a distinctive gene profile, whether that gene profile is maintained in fibroblasts cultured from SSc skin biopsy specimens, and whether results from tissue obtained from multiple clinical centers can be combined to yield useful observations in this rare disease. METHODS: Biopsy samples and passaged fibroblasts were stored in RNAlater solution prior to processing for RNA. RNA from SSc and control skin biopsy specimens, as well as SSc and control explanted passage 4 fibroblasts, from 9 patients and 9 controls was hybridized to Affymetrix HG-U133A arrays. Data were analyzed using the BRB ArrayTools system. When appropriate, findings were followed up with immunohistochemical analysis or TaqMan studies. RESULTS: Biopsy samples obtained from patients with SSc had a robust and distinctive gene profile, with approximately 1,800 qualifiers distinguishing normal skin from SSc skin at a significant level. The SSc phenotype was the major driver of sample clusters, independent of origin. Alterations in transforming growth factor beta and Wnt pathways, extracellular matrix proteins, and the CCN family were prominent. Explanted fibroblasts from SSc biopsy samples showed a far smaller subset of changes that were relatively variable between samples, suggesting that either nonfibroblast cell types or other aspects of the dermal milieu are required for full expression of the SSc phenotype. CONCLUSION: SSc has a distinct gene profile that is not confounded by geographic location, indicating that extended multicenter studies may be worthwhile to identify distinct subsets of disease by transcript profiling. Explanted SSc fibroblasts show an incomplete reflection of the SSc phenotype.

Adult↗
PubMed2006

A note on robust inference from a conditional Poisson model.

A randomised controlled trial to evaluate a training programme for physician-patient communication required the analysis of paired count data. The impact of departures from the Poisson assumption when paired count data are analysed through use of a conditional likelihood is illustrated. A simple approach to providing robust inference is outlined and illustrated.

Algorithms↗
PubMed2003

Functionalizing nanocrystalline metal oxide electrodes with robust synthetic redox proteins.

De novo designed synthetic redox proteins (maquettes) are structurally simpler, working counterparts of natural redox proteins. The robustness and adaptability of the maquette protein scaffold are ideal for functionalizing electrodes. A positive amino acid patch has been designed into a maquette surface for strong electrostatic anchoring to the negatively charged surfaces of nanocrystalline, mesoporous TiO(2) and SnO(2) films. Such mesoporous metal oxide electrodes offer a major advantage over conventional planar gold electrodes by facilitating formation of high optical density, spectroelectrochemically active thin films with protein loading orders of magnitude greater (up to 8 nmol cm(-2)) than that achieved with gold electrodes. The films are stable for weeks, essentially all immobilized-protein display rapid, reversible electrochemistry. Furthermore, carbon monoxide ligand binding to the reduced heme group of the protein is maintained, can be sensed optically and reversed electrochemically. Pulsed UV excitation of the metal oxide results in microsecond or faster photoreduction of an immobilized cytochrome and millisecond reoxidation. Upon substitution of the heme-group Fe by Zn, the light-activated maquette injects electrons from the singlet excited state of the Zn protoporphyrin IX into the metal oxide conduction band. The kinetics of cytochrome/metal oxide interfacial electron transfer obtained from the electrochemical and photochemical data obtained are discussed in terms of the free energies of the observed reactions and the electronic coupling between the protein heme group and the metal oxide surface.

Crystallization↗
PubMed2004

Robust core-shell supramolecular assemblies based on cationic vesicles and ring-shaped [Mo154] polyoxomolybdate nanoclusters: template-directed synthesis and characterizations.

Substantial progress has been made recently in extending the supramolecular assembly of biomimetic structures to vesicle-based sophisticated nanocomposites and mesostructures. We report herein the successful preparation of unilamellar surfactant vesicles coated with a monolayer of ring-shaped [Mo(154)] polyoxometalate (POM) nanoclusters, (NH(4))(28)[Mo(154)(NO)(14)O(448)H(14)(H(2)O)(70)]. approximately 350 H(2)O, by coulomb attractions using preformed didodecyldimethylammonium bromide (DDAB) surfactant vesicles as templates. The resultant vesicle-templated supramolecular assemblies are robust (they do not disintegrate upon dehydration) both at room-temperature ambient and vacuum conditions, as characterized by conventional transmission electron microscopy (TEM) and atomic force microscopy (AFM). The flexibility of the complex soft assemblies was also revealed by AFM measurements. The effect of POM-vesicle coulomb attractions on the dimensions of the templating vesicles was also investigated by using dynamic light scattering (DLS). Although origins of the structure stability of the as-prepared supramolecular assemblies are not clear yet, the nanometer scale cavities and the related properties of macroions of the POM clusters may play an important role in it.

Journal Article↗
PubMed2005

Dichlororuthenium(IV) complex of meso-tetrakis(2,6-dichlorophenyl)porphyrin: active and robust catalyst for highly selective oxidation of arenes, unsaturated steroids, and electron-deficient alkenes by using 2,6-dichloropyridine N-oxide.

[Ru(IV)(2,6-Cl2tpp)Cl2], prepared in 90 % yield from the reaction of [Ru(VI)(2,6-Cl2tpp)O2] with Me3SiCl and structurally characterized by X-ray crystallography, is markedly superior to [Ru(IV)(tmp)Cl2], [Ru(IV)(ttp)Cl2], and [Ru(II)(por)(CO)] (por=2,6-Cl2tpp, F20-tpp, F28-tpp) as a catalyst for alkene epoxidation with 2,6-Cl2pyNO (2,6-Cl2tpp=meso-tetrakis(2,6-dichlorophenyl)porphyrinato dianion; tmp=meso-tetramesitylporphyrinato dianion; ttp=meso-tetrakis(p-tolyl)porphyrinato dianion; F20-tpp=meso-tetrakis(pentafluorophenyl)porphyrinato dianion; F28-tpp=2,3,7,8,12,13,17,18-octafluoro-5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato dianion). The "[Ru(IV)(2,6-Cl2tpp)Cl2]+2,6-Cl2pyNO" protocol oxidized, under acid-free conditions, a wide variety of hydrocarbons including 1) cycloalkenes, conjugated enynes, electron-deficient alkenes (to afford epoxides), 2) arenes (to afford quinones), and 3) Delta5-unsaturated steroids, Delta4-3-ketosteroids, and estratetraene derivatives (to afford epoxide/ketone derivatives of steroids) in up to 99 % product yield within several hours with up to 100 % substrate conversion and excellent regio- or diastereoselectivity. Catalyst [Ru(IV)(2,6-Cl2tpp)Cl2] is remarkably active and robust toward the above oxidation reactions, and turnover numbers of up to 6.4x10(3), 2.0x10(4), and 1.6x10(4) were obtained for the oxidation of alpha,beta-unsaturated ketones, arenes, and Delta5-unsaturated steroids, respectively.

Alkenes↗
PubMed2005

Synthesis and characterization of thermally robust amidinato group 13 hydride complexes.

The reactivity of two sterically bulky amidines, ArNC(R)N(H)Ar (Ar=2,6-diisopropylphenyl; R=H (HFiso); tBu, (HPiso)) towards LiMH4, M=Al or Ga, [AlH3(NMe3)], and [GaH3(quin)] (quin=quinuclidine) has been examined. This has given rise to a variety of very thermally stable aluminum and gallium hydride complexes. The structural motif adopted by the prepared complexes has been found to be dependent upon both the amidinate ligand and the metal involved. The 1:1 reaction of HFiso with LiAlH4 yielded dimeric [{AlH3(mu-Fiso)Li(OEt2)}2]. Amidine HFiso reacts in a 1:1 ratio with [AlH3(NMe3)] to give the unusual hydride-bridging dimeric complex, [{AlH2(Fiso)}2], in which the Fiso- ligand is nonchelating. The equivalent reaction with the bulkier amidine, HPiso, yielded a related hydride-bridging complex, [{AlH2(Piso)}2], in which the Piso- ligand is chelating. In contrast, the treatment of [GaH3(quin)] with one equivalent of HFiso afforded the four-coordinate complex [GaH2(quin)(Fiso)], in which the Fiso- ligand acts as a localized monodentate amido-imine ligand. The 2:1 reactions of HFiso with [AlH3(NMe3)] or [GaH3(quin)] gave the monomeric complexes [MH(Fiso)2], which are thermally robust and which exhibit chelating amidinate ligands. In contrast, HPiso did not give 2:1 complexes in its reactions with either of the Group 13 trihydride precursors. For sake of comparison, the reactions of [AlH3(NMe3)] and [GaH3(quin)] with the bulky carbodiimide ArN=C=NAr and the thiourea Ar(H)NC(=S)N(H)Ar were examined. These last reactions afforded the five-coordinate thioureido complexes, [MH{N(Ar)C[N(H)(Ar)]S}2], M=Al or Ga.

Journal Article↗
PubMed2004

FocalPoint slide classification algorithms show robust performance in classification of high-grade lesions on SurePath liquid-based cervical cytology slides.

The FocalPoint Primary Screening System (FPPS) operates by assigning scores to each slide relative to the probability that an abnormality is present. This information ranks each slide within five "quintiles" (1 = highest risk, 5 = lowest risk) of the "review" population, allowing examining cytologists to understand the risk inherent in each slide. Such information helps to make the primary and quality control rescreening processes most efficient. This study examines the efficiency of AutoPap scoring and, thus, stratification of high-grade cases within a clinical trial setting. A total of 1,275 SurePath (TriPath, Burlington, NC) slides were screened on the FPPS. There were 124 high-grade cases in the set (32 HSIL, 5 AIS, and 87 cancers) as determined by cytologic truth adjudication. The efficiency of FPPS ranking was determined by analysis of the numbers of high-grade cases ranked into quintiles 1 (top 20%) and 1+2 (top 40%). FPPS places cases scored as "unsatisfactory" (HSIL, 3; Cancer, 18) into quintile 5 to ensure a manual review. These cases were excluded from the analysis. Overall, 58% of high-grade slides were classified as Q1 and 83% were classified as Q1+Q2. For HSIL, 66% were classified as Q1 and 90% as Q1+Q2. For Cancer, 59% were classified as Q1 and 84% as Q1+Q2. No high-grade slides were ranked in the lower "no review" population (slides that would receive no manual examination). The results confirm the robust performance of the FPPS classification algorithm. Far more high-grade slides are classified into the top two quintiles than would be expected by random chance alone (20% and 40%, respectively). These results validate the safety and effectiveness of this device on SurePath liquid-based slides.

Algorithms↗
PubMed1994

Robustness of individual identity in the cries of human infants.

This study investigated the possibility that one function of the human infant's cry is to convey individual identity across distance. Six-hundred adults, having been exposed to 30 s of an infant's crying, were asked to identify this infant on the basis of other, experimentally altered, cries. The cries were altered naturally by rerecording across distance in the out-of-doors, and artificially by bandpass filtering and temporal reorganization. The individuality of cries proved remarkably robust to degradation: Only when frequencies were limited to the range of 8 to 10 kHz was recognition performance significantly impaired. It is argued that the human infant's cry, a complex signal with multiple markers of individuality, may have among its functions the communication of infants' identities across distance.

Adolescent↗
PubMed2004

Cross-priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon.

"Cross-priming" refers to the activation of naive CD8+ T cells by antigen-presenting cells that have acquired nominal antigens from another cell. The biological relevance of cross-priming of CD8+ T cells has recently been challenged (Zinkernagel, R. M., Eur. J. Immunol. 2002. 32: 2385-2392), on the basis that responses are weak or poorly quantitated, and the determinants recognized are undefined. Here we show that cross-priming is a robust process that elicits vigorous primary responses to multiple peptides in two well-defined systems. Our findings support the relevance of cross-priming in CD8+ T cell responses to viruses and tumor cells, and demonstrate that cross-priming elicits CD8+ T cells to determinants generated by the endogenous processing pathway.

Animals↗
PubMed2004

Development and validation of a robust capillary electrophoresis method for impurity profiling of calcium levofolinate including the (6R,2'S)-diastereomer using statistical experimental design.

A chiral capillary electrophoresis assay for the simultaneous determination of the optical purity and of related substances of calcium levofolinate has been developed and validated. Using 2,6-dimethyl-beta-cyclodextrin as chiral selector at a concentration of 20 mg/mL, the method was optimized using a full factorial design with four factors including pH and concentration of the background electrolyte, column temperature and separation voltage. Optimized conditions were a 40 mM sodium tetraborate buffer, pH 9.9, a capillary temperature of 16 degrees C, and an applied voltage of 21 kV. Methotrexate was used as internal standard to compensate for injection errors and fluctuations of the migration times. A multiple linear regression model was also used to test the robustness of the method. Validation was performed with respect to specificity, linearity, range, limit of quantification and detection, precision, and accuracy. The assay allowed the detection and determination of related substances including the diastereomeric (6R,2'S)-impurity of levofolinic acid at the 0.1% level, the identification threshold of impurities for orally administered drugs for human use defined by the International Conference on Harmonization guidelines as well as the European Pharmacopoeia.

Borates↗
PubMed2005

A soft on-column metal coating procedure for robust sheathless electrospray emitters used in capillary electrophoresis-mass spectrometry.

An on-column metal coating procedure was developed for sheathless electrospray emitters, based on Justus von Liebig's electroless silver mirror reaction followed by electrochemical deposition of gold onto the silver layer. The coating procedure is straightforward, mild, inexpensive, and can be performed with standard laboratory equipment. A long-term (600 h) stability investigation of the conductive coating was carried out by continuous electrospray in the positive electrospray mode, and no degradation in performance was found. The simplicity of the coating procedure and the robustness of the spray tips makes the spray tips highly suitable to couple delicate wall-coated or monolithic capillary columns to mass spectrometry. Peptide mixtures were separated by capillary electrophoresis and injected into either a Hadamard-transform time-of-flight mass analyzer or a commercial quadrupole mass analyzer using the described sheathless electrospray emitters. The performance was judged to be excellent.

Electrophoresis, Capillary↗
PubMed2006

A robust cross-linked polyacrylamide coating for microchip electrophoresis of dsDNA fragments.

Surface derivatization plays an important role in microchip electrophoresis. It not only enhances the resolution, but also improves the reproducibility. So far, the most popularly used derivatization method for glass microchannels is to covalently attach a layer of linear polyacrylamide (LPA) to the channel surfaces. However, LPA coating has two problems: incomplete coverage and limited lifetime. To address these issues, we have recently developed a cross-linked polyacrylamide (CPA) derivatization protocol and demonstrated it for high-resolution protein separations by CIEF, CGE, and CZE. In this report, we used this protocol to coat microchip channels and exhibited the reliability and robustness of CPA coating for microchip electrophoresis of DNA molecules. dsDNA fragments were used as our test samples. High resolutions were obtained for fragments ranging from 100 bp to 10 kpb. After more than 800 runs, the CPA-coated microchannels still performed well and comparable resolutions were maintained throughout these runs.

Acrylic Resins↗
PubMed2006

Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system.

An enantioselective CE assay for the simultaneous determination of the enantiomeric purity and of related substances of etomidate has been developed and validated using a binary chiral selector system employing 30 mg/mL beta-CD and 4.6 mg/mL sulfated-beta-CD in a 150 mM potassium phosphate buffer, pH 2.1. The method was validated with respect to specificity, range, linearity, LOQ and LOD, precision and accuracy. The assay allowed the detection and determination of related substances including (S)-etomidate at the 0.05% w/w level, the reporting threshold as defined by the International Conference on Harmonisation guidelines as well as the European Pharmacopoeia. Robustness testing was carried out by an "Augmented Plackett-Burman" design. Quantitation of the compounds was performed by calibration graphs with respect to lidocaine hydrochloride as internal standard and by peak area normalization, the procedure usually applied by pharmacopoeias. Although data obtained from the calibration graphs constructed with the aid of the internal standard were more accurate based on compound recovery, peak area normalization may also be used without significant loss of accuracy and precision.

Cyclodextrins↗
PubMed2003

Robustness of inference on measured covariates to misspecification of genetic random effects in family studies.

Family studies to identify disease-related genes frequently collect only families with multiple cases. It is often desirable to determine if risk factors that are known to influence disease risk in the general population also play a role in the study families. If so, these factors should be incorporated into the genetic analysis to control for confounding. Pfeiffer et al. [2001 Biometrika 88: 933-948] proposed a variance components or random effects model to account for common familial effects and for different genetic correlations among family members. After adjusting for ascertainment, they found maximum likelihood estimates of the measured exposure effects. Although it is appealing that this model accounts for genetic correlations as well as for the ascertainment of families, in order to perform an analysis one needs to specify the distribution of random genetic effects. The current work investigates the robustness of the proposed model with respect to various misspecifications of genetic random effects in simulations. When the true underlying genetic mechanism is polygenic with a small dominant component, or Mendelian with low allele frequency and penetrance, the effects of misspecification on the estimation of fixed effects in the model are negligible. The model is applied to data from a family study on nasopharyngeal carcinoma in Taiwan.

Analysis of Variance↗
PubMed1987

Robust inference for variance components models in families ascertained through probands: II. Analysis of spirometric measures.

Three spirometric measures of pulmonary function were used to estimate genetic and nongenetic components of variance for 781 members of 158 families ascertained through a proband with obstructive pulmonary disease. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and the ratio of these two (FEV1/FVC) were adjusted for age, sex, race, smoking, and height and used in a robust approach to estimate variance components after conditioning on the proband's observed value. The best fitting model for both residual FEV1/FVC and FEV1 included an additive genetic component representing 25% and 9% of the variation in these two traits, respectively. In addition, there was a significant correlation between parents in residual FEV1/FVC, and a component shared among full sibs was statistically significant for residual FEV1. No evidence of a genetic component for residual FVC was found in this analysis. Although these results agree with previous reports based on other populations in showing a substantial degree of direct genetic control over spirometric measures of pulmonary function, they also raise the possibility of etiologic heterogeneity.

Analysis of Variance↗