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We present a data assimilation package for use with ocean circulation models in analysis, forecasting, and system evaluation applications. The basic functionality of the package is centered on a multivariate linear statistical estimation for a given predicted/background ocean state, observations, and error statistics. Novel features of the package include support for multiple covariance models, and the solution of the least squares normal equations either using the covariance matrix or its inverse—the information matrix. The main focus of this paper, however, is on the solution of the analysis equations using the information matrix, which offers several advantages for solving large problems efficiently. Details of the parameterization of the inverse covariance using Markov random fields are provided and its relationship to finite-difference discretizations of diffusion equations are pointed out. The package can assimilate a variety of observation types from both remote sensing and in situ platforms. The performance of the data assimilation methodology implemented in the package is demonstrated with a yearlong global ocean hindcast with a 1/4° ocean model. The code is implemented in modern Fortran, supports distributed memory, shared memory, multicore architectures, and uses climate and forecasts compliant Network Common Data Form for input/output. The package is freely available with an open source license from www.tendral.com/tsis/.

We assess and compare four sequential data assimilation methods developed for HYCOM in an identical twin experiment framework. The methods considered are Multi-variate Optimal Interpolation (MVOI), Ensemble Optimal Interpolation (EnOI), the fixed basis version of the Singular Evolutive Extended Kalman Filter (SEEK) and the Ensemble Reduced Order Information Filter (EnROIF). All methods can be classified as statistical interpolation but differ mainly in how the forecast error covariances are modeled. Surface elevation and temperature data sampled from an 1/12 Gulf of Mexico HYCOM simulation designated as the truth are assimilated into an identical model starting from an erroneous initial state, and convergence of assimilative runs towards the truth is tracked. Sensitivity experiments are first performed to evaluate the impact of practical implementation choices such as the state vector structure, initialization procedures, correlation scales, covariance rank and details of handling multivariate datasets, and to identify an effective configuration for each assimilation method. The performance of the methods are then compared by examining the relative convergence of the assimilative runs towards the truth. All four methods show good skill and are able to enhance consistency between the assimilative and truth runs in both observed and unobserved model variables. Prediction errors in observed variables are typically less than the errors specified for the observations, and the differences between the assimilated products are small compared to the observation errors. For unobserved variables, RMS errors are reduced by 50% relative to a non-assimilative run and differ between schemes on average by about 5%. Dynamical consistency between the updated state space variables in the data assimilation algorithm, and the data adequately sampling significant dynamical features are the two crucial components for reliable predictions. The experiments presented here suggest that practical implementation details can have at least as much an impact on the accuracy of the assimilated product as the choice of assimilation technique itself. We also present a discussion of the numerical implementation and the computational requirements for the use of these methods in large scale applications.

Monte Carlo computational methods have been introduced into data assimilation for nonlinear systems in order to alleviate the computational burden of updating and propagating the full probability distribution. By propagating an ensemble of representative states, algorithms like the ensemble Kalman filter (EnKF) and the resampled particle filter (RPF) rely on the existing modeling infrastructure to approximate the distribution based on the evolution of this ensemble. This work presents an ensemble-based smoother that is applicable to the Monte Carlo filtering schemes like EnKF and RPF. At the minor cost of retrospectively updating a set of weights for ensemble members, this smoother has demonstrated superior capabilities in state tracking for two highly nonlinear problems: the double-well potential and trivariate Lorenz systems. The algorithm does not require retrospective adaptation of the ensemble members themselves, and it is thus suited to a streaming operational mode. The accuracy of the proposed backward-update scheme in estimating non-Gaussian distributions is evaluated by comparison to the more accurate estimates provided by a Markov chain Monte Carlo algorithm.

Some applications in remote sensing require estimating a field containing a discontinuity whose exact location is a priori unknown. Such fields of interest include sea surface temperature in oceanography and soil moisture in hydrology. For the former, oceanic fronts form a temperature discontinuity, while in the latter sharp changes exist across the interface between soil types. To complicate the estimation process, remotely sensed measurements often exhibit regions of missing observations due to occlusions such as cloud cover. Similarly, water surface and ground-based sensors usually provide only an incomplete set of measurements. Traditional methods of interpolation and smoothing for estimating the fields from such potentially sparse measurements often blur across the discontinuities in the field.

The reaction of toluene diisocyanate with 2,2,3,3-tetrafluoro-1-propanol (fluoro compound) or 3-glycidoxypropyl trimethoxysilane(siloxane compound) and other additives to form the structure of the fluoro-based or siloxane-based polyurethane (PU) ionomer has been proven by infrared spectra. Experimental results indicated that the amount of water vapor permeability of the film made by fluoro-based or siloxane-based PU ionomer appeared to gradually increase with increasing concentration of the siloxane compound or fluoro compound, as a result of the formation of more porosities. Our experimental results also showed that the water vapor absorption was seen to be larger for the film made by siloxane-based PU ionomer film than for the film made by fluoro-based PU ionomer film, as a result of increased hydrophilic groups attached to the backbone of the PU ionomer molecule. For the film prepared by siloxane-based PU ionomer, both tensile strength and elongation appeared to increase with an increase in the concentration of siloxane compound. This may be the result of the intermolecular interaction between siloxane-based PU ionomer molecules themselves, thus enhancing the crosslinking capability of the ionomer molecules. On the other hand, both tensile strength and elongation for the film prepared by fluoro-based PU ionomer decreased with increasing concentration of the fluoro compound, as a result of intramolecular interaction greatly reducing the crosslinking capability of the ionomer molecules. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3767–3773, 2006

Sixth-five 14-thalassaemia genes from 14 unrelated Chinese β-thalassaemia major patients and 37 Chinese β-carriers were analysed by allele-specific oligonucleotide (ASO) hybridization after DNA amplification by the polymerase chain reaction (PGR). Six mutations were studied and are represented by 49.2% of codon 41-42, 30.8% of IVSII #654, 6.2% of 17β 3.1% of IVSI #5 (G→G) and 1.5% of -28 TATA box. The complete mutations responsible for β-thalassaemia major in 13 of our 14 affected families were identified. For these families prenatal diagnosis at 10 weeks gestation using DNA amplification and ASO hybridization will replace the globin chain biosynthesis technique at 19 weeks gestation

X-ray diffraction analysis at 1.5 A resolution has confirmed the helical conformation of a de novo designed 18-residue peptide. However, the crystal structure reveals the formation of continuous molecular layers of parallel-packed amphiphilic helices as a result of much more extensive helix-helix interactions than predicted. The crystal packing arrangement, by virtue of distinct antiparallel packing interactions, segregates the polar and apolar surfaces of the helices into discrete and well-defined interfacial regions. An extensive "ridges-into-grooves" interdigitation characterizes the hydrophobic interface, whereas an extensive network of salt bridges and hydrogen bonds dominates the corresponding hydrophilic interface.

To compare the rejection rates of non-small cell lung cancer (NSCLC) samples obtained by differing sampling methods for testing by Sanger sequencing for epidermal growth factor receptor (EGFR) mutations. To assess the association between unsatisfactory outcomes and the quantity of DNA extracted from cytological versus histological samples.Six hundred and seventy NSCLC samples referred to our centre from 2008 to 2010 were reviewed as a consequence of sample rejection, presence of EGFR mutations, cytological versus histological sampling methods, DNA quantity and the unsatisfactory genotyping rate.Eighty samples were rejected for testing in similar proportions of histological and cytological samples (11.9% versus 10.9%) usually (n = 75) because the amount of cellular material was judged insufficient in small biopsies or cytology samples. The remaining 590 samples on which EGFR testing was attempted yielded 51 (8.6%) unsatisfactory test outcomes caused by failure of the polymerase chain reaction (PCR) (n = 47 cases), uninterpretable Sanger chromatograms (n = 3 cases) and insufficient DNA extracted for PCR (n = 1 case). The difference in rates of unsatisfactory outcomes between cytological samples (seven of 147 samples or 4.7%) versus tissue samples (44 of 443 samples or 9.9%) was clinically relevant but not statistically significant (Mann-Whitney test; P0.081). There was no association between the concentration of DNA extracted and the likelihood of an unsatisfactory analysis; which was similar in all types of sections (large and small) while 0% of 37 cytology slides were unsatisfactory.Utilizing cytology samples for EGFR testing avoids unnecessary patient re-biopsing and yields a clinically superior satisfactory rate to the overall satisfactory rate of tissue biopsies of NSCLC. The quality rather than quantity of DNA extracted may be a more important determinant of a satisfactory result.

A broad partnership of institutions is collaborating in developing and demonstrating the performance and application of eddy-resolving, real-time global and basin-scale ocean prediction systems using the HYbrid Coordinate Ocean Model (HYCOM). These systems are to be transitioned for operational use by the U.S. Navy at both the Naval Oceanographic Office (NAVOCEANO), Stennis Space Center, MS, and the Fleet Numerical Meteorology and Oceanography Center (FNMOC), Monterey, CA, and by NOAA at the National Centers for Environmental Prediction (NCEP), Washington, D.C. The systems will run efficiently on a variety of massively parallel computers and will include sophisticated, but relatively inexpensive, data assimilation techniques for assimilation of satellite altimeter sea surface height (SSH) and sea surface temperature (SST) as well as in-situ temperature, salinity, and float displacement. The partnership represents a truly broad spectrum of the oceanographic community, bringing together academia, federal agencies, and industry/commercial entities, spanning modeling, data assimilation, data management and serving, observational capabilities, and application of HYCOM prediction system outputs. The institutions participating in this Partnership have long histories of supporting and carrying out a wide range of oceanographic and ocean prediction-related research and data management. All institutions are committed to validating an operational hybrid-coordinate ocean model that combines the strengths of the vertical coordinates used in the present generation of ocean models by placing them where they perform best.

We describe an interesting patient with penicillamine-induced dermopathy.A 49-year-old woman presented with a 1-year history of recurrent haemorrhagic blisters, milia and purpura over both her elbows, while on long-term penicillamine therapy (1.5 g daily) for Wilson's disease. Histologically, dermal elastin fibres were markedly reduced in the affected areas, consistent with penicillamine-induced elastolysis.The patient's lesions improved significantly after reduction of her penicillamine dose to 500 mg daily.The cutaneous side effects of long-term penicillamine therapy are important to recognise as they may be associated with significant morbidity and may be markers of more ominous underlying systemic elastic fibre damage.

X-ray diffraction analysis at 1.5 A resolution has confirmed the helical conformation of a de novo designed 18-residue peptide. However, the crystal structure reveals the formation of continuous molecular layers of parallel-packed amphiphilic helices as a result of much more extensive helix-helix interactions than predicted. The crystal packing arrangement, by virtue of distinct antiparallel packing interactions, segregates the polar and apolar surfaces of the helices into discrete and well-defined interfacial regions. An extensive "ridges-into-grooves" interdigitation characterizes the hydrophobic interface, whereas an extensive network of salt bridges and hydrogen bonds dominates the corresponding hydrophilic interface.

beta-Thalassaemia major patients have chronic anaemia and since 3-4 per cent of Singaporeans carry the beta-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of beta-major. Six mutations along the beta-gene were studied--41-42 (-TCTT), IVSII #654 (C-T), 17 beta (A-T), -28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54.6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the beta-trait carrying the 41-42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the beta-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at -29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our beta-thalassaemia prenatal diagnosis programme in Singapore.

Sixty-five beta-thalassaemia genes from 14 unrelated Chinese beta-thalassaemia major patients and 37 Chinese beta-carriers were analysed by allele-specific oligonucleotide (ASO) hybridization after DNA amplification by the polymerase chain reaction (PCR). Six mutations were studied and are represented by 49.2% of codon 41-42, 30.8% of IVSII #654, 6.2% of 17 beta, 3.1% of IVSI #5 (G--C) and 1.5% of -28 TATA box. The complete mutations responsible for beta-thalassaemia major in 13 of our 14 affected families were identified. For these families prenatal diagnosis at 10 weeks gestation using DNA amplification and ASO hybridization will replace the globin chain biosynthesis technique at 19 weeks gestation. Using ASO analysis, our results indicate that 5 oligo-probes (41-42, II-#654, 17 beta, IVSI-#5 and -28) allow determination of beta-thalassaemia mutations in 59/65 (90.8%) of the Singaporean Chinese studied.

The authors describe their perspective on the modeling of cardiac rhythms as a component of cardiac arrhythmia signal-processing algorithms. They emphasize that these models are for a specific end purpose and that the aspects of cardiac behavior that are captured by the models are only those relevant for the development of the signal-processing algorithms. The approach is to use statistics to describe ranges of cardiac behavior that share some common feature with respect to the purpose of the signal processing. The statistical approach has the advantage that, coupled with a statistical performance criterion, it specifies an optimal signal-processing algorithm. These optimal algorithms are often computationally intractable, however, especially for real-time use in instruments. Approximations are therefore crucial. The mathematical form of the model is then important since, even if two forms generate identical statistics, the approximations that are natural in different forms can be quite different. Two different mathematical formulations are described--stochastic Petri nets and interacting Markov chains--and the different types of approximately optimal signal-processing algorithms that are natural in these two frameworks are discussed.

We describe a methodology for modeling heart rhythms observed in electrocardiograms. In particular, we present a procedure to derive simple dynamic models that capture the cardiac mechanisms which control the particular timing sequences of P and R waves characteristic of different arrhythmias. By treating the cardiac electrophysiology at an aggregate level, simple network models of the wave generating system under a variety of diseased conditions can be developed. These network models are then systematically converted to stochastic Petri nets which offer a compact mathematical framework to express the dynamics and statistical variability of the wave generating mechanisms. Models of several arrhythmias are included in order to illustrate the methodology.