960 resultados para Error in essence
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Objective: The PEM Flex Solo II (Naviscan, Inc., San Diego, CA) is currently the only commercially-available positron emission mammography (PEM) scanner. This scanner does not apply corrections for count rate effects, attenuation or scatter during image reconstruction, potentially affecting the quantitative accuracy of images. This work measures the overall quantitative accuracy of the PEM Flex system, and determines the contributions of error due to count rate effects, attenuation and scatter. Materials and Methods: Gelatin phantoms were designed to simulate breasts of different sizes (4 – 12 cm thick) with varying uniform background activity concentration (0.007 – 0.5 μCi/cc), cysts and lesions (2:1, 5:1, 10:1 lesion-to-background ratios). The overall error was calculated from ROI measurements in the phantoms with a clinically relevant background activity concentration (0.065 μCi/cc). The error due to count rate effects was determined by comparing the overall error at multiple background activity concentrations to the error at 0.007 μCi/cc. A point source and cold gelatin phantoms were used to assess the errors due to attenuation and scatter. The maximum pixel values in gelatin and in air were compared to determine the effect of attenuation. Scatter was evaluated by comparing the sum of all pixel values in gelatin and in air. Results: The overall error in the background was found to be negative in phantoms of all thicknesses, with the exception of the 4-cm thick phantoms (0%±7%), and it increased with thickness (-34%±6% for the 12-cm phantoms). All lesions exhibited large negative error (-22% for the 2:1 lesions in the 4-cm phantom) which increased with thickness and with lesion-to-background ratio (-85% for the 10:1 lesions in the 12-cm phantoms). The error due to count rate in phantoms with 0.065 μCi/cc background was negative (-23%±6% for 4-cm thickness) and decreased with thickness (-7%±7% for 12 cm). Attenuation was a substantial source of negative error and increased with thickness (-51%±10% to -77% ±4% in 4 to 12 cm phantoms, respectively). Scatter contributed a relatively constant amount of positive error (+23%±11%) for all thicknesses. Conclusion: Applying corrections for count rate, attenuation and scatter will be essential for the PEM Flex Solo II to be able to produce quantitatively accurate images.
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Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous within an infected patient and among individuals. Substitution rates in the virus genomes are high and vary in different lineages and among sites. Methods of phylogenetic analysis were applied to study the evolution of primate lentiviruses and the hepatitis delta virus. The following results have been obtained: (1) The substitution rate varies among sites of primate lentivirus genes according to the two parameter gamma distribution, with the shape parameter $\alpha$ being close to 1. (2) Primate immunodeficiency viruses fall into species-specific lineages. Therefore, viral transmissions across primate species are not as frequent as suggested by previous authors. (3) Primate lentiviruses have acquired or lost their pathogenicity several times in the course of evolution. (4) Evidence was provided for multiple infections of a North American patient by distinct HIV-1 strains of the B subtype. (5) Computer simulations indicate that the probability of committing an error in testing HIV transmission depends on the number of virus sequences and their length, the divergence times among sequences, and the model of nucleotide substitution. (6) For future investigations of HIV-1 transmissions, using longer virus sequences and avoiding the use of distant outgroups is recommended. (7) Hepatitis delta virus strains are usually related according to the geographic region of isolation. (8) Evolution of HDV is characterized by the rate of synonymous substitution being lower than the nonsynonymous substitution rate and the rate of evolution of the noncoding region. (9) There is a strong preference for G and C nucleotides at the third codon positions of the HDV coding region. ^
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Environmental data sets of pollutant concentrations in air, water, and soil frequently include unquantified sample values reported only as being below the analytical method detection limit. These values, referred to as censored values, should be considered in the estimation of distribution parameters as each represents some value of pollutant concentration between zero and the detection limit. Most of the currently accepted methods for estimating the population parameters of environmental data sets containing censored values rely upon the assumption of an underlying normal (or transformed normal) distribution. This assumption can result in unacceptable levels of error in parameter estimation due to the unbounded left tail of the normal distribution. With the beta distribution, which is bounded by the same range of a distribution of concentrations, $\rm\lbrack0\le x\le1\rbrack,$ parameter estimation errors resulting from improper distribution bounds are avoided. This work developed a method that uses the beta distribution to estimate population parameters from censored environmental data sets and evaluated its performance in comparison to currently accepted methods that rely upon an underlying normal (or transformed normal) distribution. Data sets were generated assuming typical values encountered in environmental pollutant evaluation for mean, standard deviation, and number of variates. For each set of model values, data sets were generated assuming that the data was distributed either normally, lognormally, or according to a beta distribution. For varying levels of censoring, two established methods of parameter estimation, regression on normal ordered statistics, and regression on lognormal ordered statistics, were used to estimate the known mean and standard deviation of each data set. The method developed for this study, employing a beta distribution assumption, was also used to estimate parameters and the relative accuracy of all three methods were compared. For data sets of all three distribution types, and for censoring levels up to 50%, the performance of the new method equaled, if not exceeded, the performance of the two established methods. Because of its robustness in parameter estimation regardless of distribution type or censoring level, the method employing the beta distribution should be considered for full development in estimating parameters for censored environmental data sets. ^
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“Cultural diversity” has become one of the latest buzzwords on the international policymaking scene. It is employed in various contexts – sometimes as a term close to “biological diversity”, at other times as correlated to the “exception culturelle” and most often, as a generic concept that is mobilised to counter the perceived negative effects of economic globalisation. While no one has yet provided a precise definition of what cultural diversity is, what we can observe is the emergence of the notion of cultural diversity as incorporating a distinct set of policy objectives and choices at the global level. These decisions are not confined, as one might have expected, to cultural policymaking, but rather spill over to multiple governance domains because of the complex linkages inherent to the simultaneous pursuit of economic and other societal goals that cultural diversity encompasses and has effects on. Accounting for these intricate interdependencies, the present article clarifies the origins of the concept of cultural diversity as understood in global law and traces its evolution over time. Observing the dynamics of the concept and the surrounding political and legal developments, the article explores its justification and overall impact on the global legal regime, as well as its discrete effects on different domains of policymaking, such as media, intellectual property and culture. While the analysis is legal in essence, the article is meant to speak also to a broader transdisciplinary public. The article is part of the speacial issue on ethnic diversity and cultural pluralism, which is available under the creative commons licence: http://www.mdpi.com/journal/diversity/special_issues/ethnic-diversity/.
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Background: Individuals with type 1 diabetes (T1D) have to count the carbohydrates (CHOs) of their meal to estimate the prandial insulin dose needed to compensate for the meal’s effect on blood glucose levels. CHO counting is very challenging but also crucial, since an error of 20 grams can substantially impair postprandial control. Method: The GoCARB system is a smartphone application designed to support T1D patients with CHO counting of nonpacked foods. In a typical scenario, the user places a reference card next to the dish and acquires 2 images with his/her smartphone. From these images, the plate is detected and the different food items on the plate are automatically segmented and recognized, while their 3D shape is reconstructed. Finally, the food volumes are calculated and the CHO content is estimated by combining the previous results and using the USDA nutritional database. Results: To evaluate the proposed system, a set of 24 multi-food dishes was used. For each dish, 3 pairs of images were taken and for each pair, the system was applied 4 times. The mean absolute percentage error in CHO estimation was 10 ± 12%, which led to a mean absolute error of 6 ± 8 CHO grams for normal-sized dishes. Conclusion: The laboratory experiments demonstrated the feasibility of the GoCARB prototype system since the error was below the initial goal of 20 grams. However, further improvements and evaluation are needed prior launching a system able to meet the inter- and intracultural eating habits.
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We present successful 81 Kr-Kr radiometric dating of ancient polarice. Krypton was extracted from the air bubbles in four∼350-kg polar ice samples from Taylor Glacier in the McMurdo Dry Valleys, Antarctica, and dated using Atom Trap Trace Analysis (ATTA). The 81 Kr radiometric ages agree with independent age estimates obtained from stratigraphic dating techniques with a mean abso-lute age offset of 6±2.5 ka. Our experimental methods and sampling strategy are validated by (i) 85 Kr and 39 Ar analyses that show the samples to be free of modern air contamination and (ii)air content measurements that show the ice did not experience gas loss. We estimate the error in the 81 Kr ages due to past geomagnetic variability to be below 3 ka. We show that ice from the previous interglacial period (Marine Isotope Stage 5e, 130–115 ka before present) can be found in abundance near the surface of Taylor Glacier. Our study paves the way for reliable radiometric dating of ancient ice in blue ice areas and margin sites where large samples are available, greatly enhancing their scientific value as archives of old ice and meteorites. At present, ATTA 81Kr analysis requires a 40–80-kg ice sample; as sample requirements continue to decrease, 81 Kr dating of ice cores is a future possibility.
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The concentrations of chironomid remains in lake sediments are very variable and, therefore, chironomid stratigraphies often include samples with a low number of counts. Thus, the effect of low count sums on reconstructed temperatures is an important issue when applying chironomid‐temperature inference models. Using an existing data set, we simulated low count sums by randomly picking subsets of head capsules from surface‐sediment samples with a high number of specimens. Subsequently, a chironomid‐temperature inference model was used to assess how the inferred temperatures are affected by low counts. The simulations indicate that the variability of inferred temperatures increases progressively with decreasing count sums. At counts below 50 specimens, a further reduction in count sum can cause a disproportionate increase in the variation of inferred temperatures, whereas at higher count sums the inferences are more stable. Furthermore, low count samples may consistently infer too low or too high temperatures and, therefore, produce a systematic error in a reconstruction. Smoothing reconstructed temperatures downcore is proposed as a possible way to compensate for the high variability due to low count sums. By combining adjacent samples in a stratigraphy, to produce samples of a more reliable size, it is possible to assess if low counts cause a systematic error in inferred temperatures.
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The goal of this study was to investigate the properties of human acid (alpha)-glucosidase with respect to: (i) the molecular heterogeneity of the enzyme and (ii) the synthesis, post-translational modification, and transport of acid (alpha)-glucosidase in human fibroblasts.^ The initial phase of these investigations involved the purification of acid (alpha)-glucosidase from the human liver. Human hepatic acid (alpha)-glucosidase was characterized by isoelectric focusing and native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Four distinct charge forms of hepatic acid (alpha)-glucosidase were separated by chromatofocusing and characterized individually. Charge heterogeneity was demonstrated to result from differences in the polypeptide components of each charge form.^ The second aspect of this research focused on the biosynthesis and the intracellular processing and transport of acid (alpha)-glucosidase in human fibroblasts. These experiments were accomplished by immune precipitation of the biosynthetic intermediates of acid (alpha)-glucosidase from radioactively labeled fibroblasts with polyclonal and monoclonal antibodies raised against human hepatic acid (alpha)-glucosidase. The immune precipitated biosynthetic forms of acid (alpha)-glucosidase were analyzed by SDS-PAGE and autoradiography. The pulse-chase experiments demonstrated the existence of several transient, high molecular weight precursors of acid (alpha)-glucosidase. These precursors were demonstrated to be intermediates of acid (alpha)-glucosidase at different stages of transport and processing in the Golgi apparatus. Other experiments were performed to examine the role of co-translational glycosylation of acid (alpha)-glucosidase in the transport and processing of precursors of this enzyme.^ A specific immunological assay for detecting acid (alpha)-glucosidase was developed using the monoclonal antibodies described above. This method was modified to increase the sensitivity of the assay by utilization of the biotin-avidin amplification system. This method was demonstrated to be more sensitive for detecting human acid (alpha)-glucosidase than the currently used biochemical assay for acid (alpha)-glucosidase activity. It was also demonstrated that the biotin-avidin immunoassay could discriminate between normal and acid (alpha)-glucosidase deficient fibroblasts, thus providing an alternative approach to detecting this inborn error in metabolism. (Abstract shortened with permission of author.) ^
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Radiation therapy for patients with intact cervical cancer is frequently delivered using primary external beam radiation therapy (EBRT) followed by two fractions of intracavitary brachytherapy (ICBT). Although the tumor is the primary radiation target, controlling microscopic disease in the lymph nodes is just as critical to patient treatment outcome. In patients where gross lymphadenopathy is discovered, an extra EBRT boost course is delivered between the two ICBT fractions. Since the nodal boost is an addendum to primary EBRT and ICBT, the prescription and delivery must be performed considering previously delivered dose. This project aims to address the major issues of this complex process for the purpose of improving treatment accuracy while increasing dose sparing to the surrounding normal tissues. Because external beam boosts to involved lymph nodes are given prior to the completion of ICBT, assumptions must be made about dose to positive lymph nodes from future implants. The first aim of this project was to quantify differences in nodal dose contribution between independent ICBT fractions. We retrospectively evaluated differences in the ICBT dose contribution to positive pelvic nodes for ten patients who had previously received external beam nodal boost. Our results indicate that the mean dose to the pelvic nodes differed by up to 1.9 Gy between independent ICBT fractions. The second aim is to develop and validate a volumetric method for summing dose of the normal tissues during prescription of nodal boost. The traditional method of dose summation uses the maximum point dose from each modality, which often only represents the worst case scenario. However, the worst case is often an exaggeration when highly conformal therapy methods such as intensity modulated radiation therapy (IMRT) are used. We used deformable image registration algorithms to volumetrically sum dose for the bladder and rectum and created a voxel-by-voxel validation method. The mean error in deformable image registration results of all voxels within the bladder and rectum were 5 and 6 mm, respectively. Finally, the third aim explored the potential use of proton therapy to reduce normal tissue dose. A major physical advantage of protons over photons is that protons stop after delivering dose in the tumor. Although theoretically superior to photons, proton beams are more sensitive to uncertainties caused by interfractional anatomical variations, and must be accounted for during treatment planning to ensure complete target coverage. We have demonstrated a systematic approach to determine population-based anatomical margin requirements for proton therapy. The observed optimal treatment angles for common iliac nodes were 90° (left lateral) and 180° (posterior-anterior [PA]) with additional 0.8 cm and 0.9 cm margins, respectively. For external iliac nodes, lateral and PA beams required additional 0.4 cm and 0.9 cm margins, respectively. Through this project, we have provided radiation oncologists with additional information about potential differences in nodal dose between independent ICBT insertions and volumetric total dose distribution in the bladder and rectum. We have also determined the margins needed for safe delivery of proton therapy when delivering nodal boosts to patients with cervical cancer.
New methods for quantification and analysis of quantitative real-time polymerase chain reaction data
Resumo:
Quantitative real-time polymerase chain reaction (qPCR) is a sensitive gene quantitation method that has been widely used in the biological and biomedical fields. The currently used methods for PCR data analysis, including the threshold cycle (CT) method, linear and non-linear model fitting methods, all require subtracting background fluorescence. However, the removal of background fluorescence is usually inaccurate, and therefore can distort results. Here, we propose a new method, the taking-difference linear regression method, to overcome this limitation. Briefly, for each two consecutive PCR cycles, we subtracted the fluorescence in the former cycle from that in the later cycle, transforming the n cycle raw data into n-1 cycle data. Then linear regression was applied to the natural logarithm of the transformed data. Finally, amplification efficiencies and the initial DNA molecular numbers were calculated for each PCR run. To evaluate this new method, we compared it in terms of accuracy and precision with the original linear regression method with three background corrections, being the mean of cycles 1-3, the mean of cycles 3-7, and the minimum. Three criteria, including threshold identification, max R2, and max slope, were employed to search for target data points. Considering that PCR data are time series data, we also applied linear mixed models. Collectively, when the threshold identification criterion was applied and when the linear mixed model was adopted, the taking-difference linear regression method was superior as it gave an accurate estimation of initial DNA amount and a reasonable estimation of PCR amplification efficiencies. When the criteria of max R2 and max slope were used, the original linear regression method gave an accurate estimation of initial DNA amount. Overall, the taking-difference linear regression method avoids the error in subtracting an unknown background and thus it is theoretically more accurate and reliable. This method is easy to perform and the taking-difference strategy can be extended to all current methods for qPCR data analysis.^
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The rate at which hydrothermal precipitates accumulate, as measured by the accumulation rate of manganese, can be used to identify periods of anomalous hydrothermal activity in the past. From a preliminary study of Sites 597 and 598, four periods prior to 6 Ma of anomalously high hydrothermal activity have been identified: 8.5 to 10.5 Ma, 12 to 16 Ma, 17 to 18 Ma, and 23-to-27 Ma. The 18-Ma anomaly is the largest and is associated with the jump in spreading from the fossil Mendoza Ridge to the East Pacific Rise, whereas the 23-to-27-Ma anomaly is correlated with the birth of the Galapagos Spreading Center and resultant ridge reorganization. The 12-to-16-Ma and 8.5-to-10.5-Ma anomalies are correlated with periods of anomalously high volcanism around the rim of the Pacific Basin and may be related to other periods of ridge reorganization along the East Pacific Rise. There is no apparent correlation between periods of fast spreading at 19°S and periods of high hydrothermal activity. We thus suggest that periods when hydrothermal activity and crustal alteration at mid-ocean ridges are the most pronounced may be periods of large-scale ridge reorganization.
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We present a high-resolution magnetostratigraphy and relative paleointensity (RPI) record derived from the upper 85 meters of IODP Site U1336, an equatorial Pacific early to middle Miocene succession recovered during Expedition 320/321. The magnetostratigraphy is well resolved with reversals typically located to within a few centimeters resulting in a well-constrained age model. The lowest normal polarity interval, from 85 to 74.87 meters, is interpreted as the upper part of Chron C6n (18.614-19.599 Ma). Another 33 magnetozones occur from 74.87 to 0.85 m, which are interpret to represent the continuous sequence of chrons from Chron C5Er (18.431-18.614 Ma) up to the top of Chron C5An.1n (12.014 Ma). We identify three new possible subchrons within Chron C5Cn.1n, Chron 5Bn.1r, and C5ABn. Sedimentation rates vary from about 7 to 15 m/Myr with a mean of about 10 m/Myr. We observe rapid, apparent changes in the sedimentation rate at geomagnetic reversals between ~16 and 19 Ma that indicate a calibration error in geomagnetic polarity timescale (ATNTS2004). The remanence is carried mainly by non-interacting particles of fine-grained magnetite, which have FORC distributions characteristic of biogenic magnetite. Given the relative homogeneity of the remanence carriers throughout the 85-m-thick succession and the quality with which the remanence is recorded, we have constructed a relative paleointensity (RPI) record that provides new insights into middle Miocene geomagnetic field behavior. The RPI record indicates a gradual decline in field strength between 18.5 Ma and 14.5 Ma, and indicates no discernible link between RPI and either chron duration or polarity state.
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Peridotites (diopside-bearing harzburgites) found at 13°N of the Mid-Atlantic Ridge fall into two compositional groups. Peridotites P1 are plagioclase-free rocks with minerals of uniform composition and Ca-pyroxene strongly depleted in highly incompatible elements. Peridotites P2 bear evidence of interaction with basic melt: mafic veinlets; wide variations in mineral composition; enrichment of minerals in highly incompatible elements (Na, Zr, and LREE); enrichment of minerals in moderately incompatible elements (Ti, Y, and HREE) from P1 level to abundances 4-10 times higher toward the contacts with mafic aggregates; and exotic mineral assemblages Cr-spinel + rutile and Cr-spinel + ilmenite in peridotite and pentlandite + rutile in mafic veinlets. Anomalous incompatible-element enrichment of minerals from peridotites P2 occurred at the spinel-plagioclase facies boundary, which corresponds to pressure of about 0.8-0.9 GPa. Temperature and oxygen fugacity were estimated from spinel-orthopyroxene-olivine equilibria. Peridotites P1 with uniform mineral composition record temperature of the last complete recrystallization at 940-1050°C and FMQ buffer oxygen fugacity within the calculation error. In peridotites P2, local assemblages have different compositions of coexisting minerals, which reflects repeated partial recrystallization during heating to magmatic temperatures (above 1200°C) and subsequent reequilibration at temperatures decreasing to 910°C and oxygen fugacity significantly higher than FMQ buffer (delta log fO2 = 1.3-1.9). Mafic veins are considered to be a crystallization product from basic melt enriched in Mg and Ni via interaction with peridotite. The geochemical type of melt reconstructed by the equilibrium with Ca-pyroxene is defined as T-MORB: (La/Sm)_N~1.6 and (Ce/Yb) )_N~2.3 that is well consistent with compositional variations of modern basaltic lavas in this segment of the Mid-Atlantic Ridge, including new data on quenched basaltic glasses.
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We present modern B/Ca core-top calibrations for the epifaunal benthic foraminifer Nuttallides umbonifera and the infaunal Oridorsalis umbonatus to test whether B/Ca values in these species can be used for the reconstruction of paleo-D[[CO3]2-]. O. umbonatus originated in the Late Cretaceous and remains extant, whereas N. umbonifera originated in the Eocene and is the closest extant relative to Nuttallides truempyi, which ranges from the Late Cretaceous through the Eocene. We measured B/Ca in both species in 35 Holocene sediment samples from the Atlantic, Pacific and Southern Oceans. B/Ca values in epifaunal N. umbonifera (~ 85-175 µmol/mol) are consistently lower than values reported for epifaunal Cibicidoides (Cibicides) wuellerstorfi (130-250 µmol/mol), though the sensitivity of D[[CO3]2-] on B/Ca in N. umbonifera (1.23 ± 0.15) is similar to that in C. wuellerstorfi (1.14 ± 0.048). In addition, we show that B/Ca values of paired N. umbonifera and its extinct ancestor, N. truempyi, from Eocene cores are indistinguishable within error. In contrast, both the B/Ca (35-85 µmol/mol) and sensitivity to D[[CO3]2-] (0.29 ± 0.20) of core-top O. umbonatus are considerably lower (as in other infaunal species), and this offset extends into the Paleocene. Thus the B/Ca of N. umbonifera and its ancestor can be used to reconstruct bottom water D[[CO3]2?], whereas O. umbonatus B/Ca appears to be buffered by porewater [[CO3]2-] and suited for constraining long-term drift in seawater B/Ca.
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Drilling at Sites 534 and 603 of the Deep Sea Drilling Project recovered thick sections of Berriasian through Aptian white limestones to dark gray marls, interbedded with claystone and clastic turbidites. Progressive thermal demagnetization removed a normal-polarity overprint carried by goethite and/or pyrrhotite. The resulting characteristic magnetization is carried predominantly by magnetite. Directions and reliability of characteristic magnetization of each sample were computed by using least squares line-fits of magnetization vectors. The corrected true mean inclinations of the sites suggest that the western North Atlantic underwent approximately 6° of steady southward motion between the Berriasian and Aptian stages. The patterns of magnetic polarity of the two sites, when plotted on stratigraphic columns of the pelagic sediments without turbidite beds, display a fairly consistent magnetostratigraphy through most of the Hauterivian-Barremian interval, using dinoflagellate and nannofossil events and facies changes in pelagic sediment as controls on the correlations. The composite magnetostratigraphy appears to include most of the features of the M-sequence block model of magnetic anomalies from Ml to Ml ON (Barremian-Hauterivian) and from M16 to M23 (Berriasian-Tithonian). The Valanginian magnetostratigraphy of the sites does not exhibit reversed polarity intervals corresponding to Ml 1 to M13 of the M-sequence model; this may be the result of poor magnetization, of a major unrecognized hiatus in the early to middle Valanginian in the western North Atlantic, or of an error in the standard block model. Based on these tentative polarity-zone correlations, the Hauterivian/Barremian boundary occurs in or near the reversed-polarity Chron M7 or M5, depending upon whether the dinoflagellate or nannofossil zonation, respectively, is used; the Valanginian/Hauterivian boundary, as defined by the dinoflagellate zonation, is near reversed-polarity Chron M10N.