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PubMed1996

Simultaneous assessment of loss of heterozygosity at multiple microsatellite loci using semi-automated fluorescence-based detection: subregional mapping of chromosome 4 in cervical carcinoma.

Detection of loss of heterozygosity (LOH) by comparison of normal and tumor genotypes using PCR-based microsatellite loci provides considerable advantages over traditional Southern blotting-based approaches. However, current methodologies are limited by several factors, including the numbers of loci that can be evaluated for LOH in a single experiment, the discrimination of true alleles versus "stutter bands," and the use of radionucleotides in detecting PCR products. Here we describe methods for high throughput simultaneous assessment of LOH at multiple loci in human tumors; these methods rely on the detection of amplified microsatellite loci by fluorescence-based DNA sequencing technology. Data generated by this approach are processed by several computer software programs that enable the automated linear quantitation and calculation of allelic ratios, allowing rapid ascertainment of LOH. As a test of this approach, genotypes at a series of loci on chromosome 4 were determined for 58 carcinomas of the uterine cervix. The results underscore the efficacy, sensitivity, and remarkable reproducibility of this approach to LOH detection and provide subchromosomal localization of two regions of chromosome 4 commonly altered in cervical tumors.

Chromosome Deletion↗
PubMed1988

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. II. Review of past studies of WIC.

We reviewed past work relating WIC benefits to birth weight, perinatal and infant survival, anemia, child growth, and dietary intake. Despite many uncertainties, the probable range of reduction in the rate of low birth weight was approximately 1-2% and the increase in mean birth weight ranged from 0 to approximately 60 g. There was too little information to securely estimate effects of WIC on perinatal and infant mortality nor on the dietary intake of women or children. Although the number of studies was small, there probably were important effects of WIC on rates of childhood anemia. There is too little evidence to come to any conclusion on effects during pregnancy. There is little evidence that the WIC program has affected children's linear growth.

Birth Weight↗
PubMed2000

Iterative sequence/secondary structure search for protein homologs: comparison with amino acid sequence alignments and application to fold recognition in genome databases.

MOTIVATION: Sequence alignment techniques have been developed into extremely powerful tools for identifying the folding families and function of proteins in newly sequenced genomes. For a sufficiently low sequence identity it is necessary to incorporate additional structural information to positively detect homologous proteins. We have carried out an extensive analysis of the effectiveness of incorporating secondary structure information directly into the alignments for fold recognition and identification of distant protein homologs. A secondary structure similarity matrix based on a database of three-dimensionally aligned proteins was first constructed. An iterative application of dynamic programming was used which incorporates linear combinations of amino acid and secondary structure sequence similarity scores. Initially, only primary sequence information is used. Subsequently contributions from secondary structure are phased in and new homologous proteins are positively identified if their scores are consistent with the predetermined error rate. RESULTS: We used the SCOP40 database, where only PDB sequences that have 40% homology or less are included, to calibrate homology detection by the combined amino acid and secondary structure sequence alignments. Combining predicted secondary structure with sequence information results in a 8-15% increase in homology detection within SCOP40 relative to the pairwise alignments using only amino acid sequence data at an error rate of 0.01 errors per query; a 35% increase is observed when the actual secondary structure sequences are used. Incorporating predicted secondary structure information in the analysis of six small genomes yields an improvement in the homology detection of approximately 20% over SSEARCH pairwise alignments, but no improvement in the total number of homologs detected over PSI-BLAST, at an error rate of 0.01 errors per query. However, because the pairwise alignments based on combinations of amino acid and secondary structure similarity are different from those produced by PSI-BLAST and the error rates can be calibrated, it is possible to combine the results of both searches. An additional 25% relative improvement in the number of genes identified at an error rate of 0.01 is observed when the data is pooled in this way. Similarly for the SCOP40 dataset, PSI-BLAST detected 15% of all possible homologs, whereas the pooled results increased the total number of homologs detected to 19%. These results are compared with recent reports of homology detection using sequence profiling methods. AVAILABILITY: Secondary structure alignment homepage at http://lutece.rutgers.edu/ssas CONTACT: anders@rutchem.rutgers.edu; ronlevy@lutece.rutgers.edu SUPPLEMENTARY INFORMATION: Genome sequence/structure alignment results at http://lutece.rutgers.edu/ss_fold_predictions.

Algorithms↗
PubMed1986

Peptide sequencing program.

A computer program has been devised to automate rationalization of peptide fragmentation patterns. The program systematically generates all possible linear amino acid sequences which might be attributable to a peptide with a known amino acid composition. The generated sequences are then searched to find those that most closely match the spectrum of an unknown sequence.

Algorithms↗
PubMed2005

Neutron cross section measurements at ORELA for improved nuclear data and their application.

To support the Nuclear Criticality Safety Program, the Oak Ridge Electron Linear Accelerator (ORELA) has been used to measure the total and capture neutron cross sections of several nuclides in the energy range from 100 eV to -600 keV. Concerns about the use of existing cross section data in nuclear criticality calculations have been a prime motivator for the new cross-section measurements. Our new capture cross sections of aluminium, silicon, chlorine, fluorine and potassium in the energy range from 100 eV to 600 keV are substantially different from the cross sections in evaluated nuclear data files of ENDF/B-VI and JENDL-3.2.

Databases, Factual↗
PubMed2004

Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy.

BACKGROUND AND OBJECTIVE: The optimal time for changing failing antiretroviral therapy (ART) is not known. It involves balancing the risk of exhausting future treatment options against the risk of developing increased drug resistance. The frequency with which new drug-resistance mutations (DRM) developed and their potential consequences in patients continuing unchanged treatment despite persistent viremia were assessed. DESIGN: A retrospective study of consecutive sequence samples from 106 patients at one institution with viral load (VL) of more than 400 copies/ml, with no change in ART for more than 2 months despite virologic failure. METHODS: Two consecutive pol sequences, CD4 cell counts and VL were analyzed to quantify the development of new DRM and to identify changes in immunologic and virologic parameters. Genotypic susceptibility scores (GSS) and viral drug susceptibilities were calculated by a computer program (HIVDB). Poisson log-linear regression models were used to predict the expected number of mutations at the second time point. RESULTS: : After a median of 14 months of continued ART, 75% (80 of 106) of patients acquired new DRM and were assigned a significantly lower GSS, potentially limiting the success of future ART. The development of new DRM was proportional to the time between the two sequences and inversely proportional to the number of DRM in the first sequence. However, the development of DRM was not associated with significant changes in CD4 or VL counts. CONCLUSIONS: Despite stable levels of CD4 and VL over time, maintaining a failing therapeutic regimen increases drug resistance and may limit future treatment options.

Adult↗
PubMed1999

Programmes in chronically vulnerable areas: challenges and lessons learned.

In the 'chronically vulnerable areas' (CVAs) of East Africa a smooth linear transition away from emergency programming towards rehabilitation and long-term development is difficult, if not impossible. This makes uncritical application of the 'relief-to-development' continuum to programming unhelpful at best, and perhaps counter-productive. This paper is the result of CARE's efforts to review its own programmes--and those of some of its sister agencies--in chronically vulnerable areas in the East Africa region, to derive important lessons learned and to identify areas where improvements are needed. The paper focuses on strategic considerations and decision-making in relation to entry, programme design and strategies for transition and exit.

Africa, Eastern↗
PubMedDate not supplied

Analytic calculation of electron beam isodose distributions.

Analytical techniques have been developed to generate electron beam isodose distributions from a modest set of experimental data. These techniques include (1) development of a compact yet powerful linear least-squares optimization program with a graphic display of the results, (2) coordinate transformations to allow straightforward fitting of the isodose distributions with simple polynomial functions, and (3) accurate interpolation methods to allow production of treatment planning dose matrices. The program, written in FORTRAN, has been implemented on a minicomputer and uses the standard peripherals of a commercially available treatment planning system (AECL TP-11). The computer-generated isodose and central-axis distributions correspond very closely with the data for electron energies from 5 to 20 MeV and for all field sizes.

Electrons↗
PubMedDate not supplied

Nutritional risk factors in major hepatobiliary surgery.

Preoperative nutritional assessment was performed for 32 patients undergoing surgery for malignant hepatobiliary and pancreatic disease. Weight, mid-arm circumference, total body potassium (TBK), and skin test reactivity were significantly reduced in the seven patients who died after operation (p less than .05, Student's t-test and Fisher's exact test). Analyses of major life-threatening complications indicated that those who had a complicated postoperative course (17 patients) had a significantly lower TBK (p less than .05, Fisher's exact test). Using linear discriminant analysis (SPSS computer program), correct prediction of postoperative death or survival was possible in 85% of patients if measured by TBK alone, and in 83% if weight loss and serum albumin were used. Seventy three percent were correctly classified as complicated or uncomplicated by TBK alone, but serum albumin and weight loss were not helpful in predicting patients with complications. This study shows that malnutrition and operative risk may be identified preoperatively in patients with malignant hepatobiliary and pancreatic disease. Objective improvement may be achieved by intensive nutritional support.

Adenocarcinoma↗
PubMed1997

Relationship of muscle strength to potassium concentration in a hypokalaemic infant.

A nine-month infant, weighing 9.8 kg, presented with hypotonia secondary to acute hypokalaemia (1.0 mmol/l). Muscle strength improved as the serum potassium was increased. Muscle strength was assessed by the pressure generated inside a saline-filled endotracheal tube cuff during a grasp reflex. Potassium concentration and hand grip strength were related using a sigmoidal Emax model. Zero effect was assumed when the potassium concentration was zero. The Emax, EC50 and Hill coefficient values were determined by non-linear regression using the MKMODEL program. Parameter estimates (SE) were EC50 1.79 (0.15) mmol/l, Hill coefficient 3.79 (0.92), Emax 114.4 (8.9) mmHg.

Acute Disease↗
PubMed2006

Automated agar plate streaker: a linear plater on Society for Biomolecular Sciences standard plates.

Several protocols for bacterial isolation and techniques for aerobic plate counting rely on the use of a spiral plater to deposit concentration gradients of microbial suspensions onto a circular agar plate to isolate colony growth. The advantage of applying a gradient of concentrations across the agar surface is that the original microbiological sample can be applied at a single concentration rather than as multiple serial dilutions. The spiral plater gradually dilutes the sample across a compact area and therefore saves time preparing dilutions and multiple agar plates. Commercial spiral platers are not automated and require manual sample loading. Dispensing of the sample volume and rate of gradients are often very limited in range. Furthermore, the spiral sample application cannot be used with rectangular microplates. Another limitation of commercial spiral platers is that they are useful only for dilute, filtered suspensions and cannot plate suspensions of coarse organic particles therefore precluding the use of many kinds of microorganism-containing substrata. An automated agar plate spreader capable of processing 99 rectangular microplates in unattended mode is described. This novel instrument is capable of dispensing discrete volumes of sample in a linear pattern. It can be programmed to dispense a sample suspense at a uniform application rate or across a decreasing concentration gradient.

Agar↗
PubMed1986

Three-compartment open model analysis of micronomicin in man.

The pharmacokinetics of micronomicin (MCR) as a model drug of aminoglycoside antibiotics (AGs) was studied in man by applying our results previously obtained in rats. Three-compartment open model analysis of combined serum and total body store (T.B.S.) data obtained from multiple dosing in man was done using a non-linear least-squares regression program MULTI. We found large individual variations of MCR disposition in man and these variations did not appear within the serum concentration range measurable with conventional assay methods. This finding suggests that the disposition of AGs, included MCR, cannot be estimated by only plasma or serum level analyses. We conclude that the therapeutic drug monitoring of AGs by using T.B.S. data analysis should be an effective method for controlling therapy with AGs in the clinical setting.

Adult↗
PubMed1989

A mathematical model on the analysis of a one-ligand, one-binding group system when an unknown amount of endogenous ligand is present.

In the study of ligand-receptor interaction, binding studies using radiolabelled ligands are usually conducted and results analyzed according to the method originally described by Scatchard. When significant levels of endogenous ligands are present, assumption of a linear relationship between the bound-to-free ratio and the bound ligand may be erroneous and chemical methods have been described to resolve this problem. We present a mathematical approach to the system, using a method based on multiple regression of binding data. A three-dimensional graphic representation of the binding data analogous to the original Scatchard plot is proposed. When the endogenous and the exogenous ligands are different, the linear regression model is applicable only if their affinity constants are known. Non-linear curve-fitting computer programs should be used to resolve this problem when these constants are unknown.

Models, Biological↗
PubMed1997

Genetic parameters for linear udder traits of dairy ewes.

An animal model was used to estimate the repeatabilities and genetic parameters of linear udder traits of Churra ewes (5265 records from 2015 ewes). In addition, the phenotypic correlations were examined between log SCC and udder traits. Heritabilities of udder depth (0.16), udder attachment (0.17), teat placement (0.24), teat size (0.18), and udder shape (0.24) were similar to those for dairy cattle, making it feasible to use data from the proposed linear system in a breeding program to improve the machine milkability of ewes. Genetic correlations among udder traits were generally favorable, implying that selection for improvement of one trait would result in improvement of others. A notable exception was the genetic correlation between teat placement and teat size of 0.62. Vertical placement of teats was associated with larger teats. Also, genetic correlations between udder and yield traits (milk and protein yields) were small, except for udder depth and teat placement. These exceptions predict worsening udder morphology from selection based solely on milk yield. Phenotypic correlations between udder traits and log SCC indicate that present handling routines led to a greater likelihood of infections for deep udders with large teats.

Animals↗
PubMed2004

Geometrical accuracy of the Novalis stereotactic radiosurgery system for trigeminal neuralgia.

OBJECT: Stringent geometrical accuracy and precision are required in the stereotactic radiosurgical treatment of patients. Accurate targeting is especially important when treating a patient in a single fraction of a very high radiation dose (90 Gy) to a small target such as that used in the treatment of trigeminal neuralgia (3 to 4-mm diameter). The purpose of this study was to determine the inaccuracies in each step of the procedure including imaging, fusion, treatment planning, and finally the treatment. The authors implemented a detailed quality-assurance program. METHODS: Overall geometrical accuracy of the Novalis stereotactic system was evaluated using a Radionics Geometric Phantom Chamber. The phantom has several magnetic resonance (MR) and computerized tomography (CT) imaging-friendly objects of various shapes and sizes. Axial 1-mm-thick MR and CT images of the phantom were acquired using a T1-weighted three-dimensional spoiled gradient recalled pulse sequence and the CT scanning protocols used clinically in patients. The absolute errors due to MR image distortion, CT scan resolution, and the image fusion inaccuracies were measured knowing the exact physical dimensions of the objects in the phantom. The isocentric accuracy of the Novalis gantry and the patient support system was measured using the Winston-Lutz test. Because inaccuracies are cumulative, to calculate the system's overall spatial accuracy, the root mean square (RMS) of all the errors was calculated. To validate the accuracy of the technique, a 1.5-mm-diameter spherical marker taped on top of a radiochromic film was fixed parallel to the x-z plane of the stereotactic coordinate system inside the phantom. The marker was defined as a target on the CT images, and seven noncoplanar circular arcs were used to treat the target on the film. The calculated system RMS value was then correlated with the position of the target and the highest density on the radiochromic film. The mean spatial errors due to image fusion and MR imaging were 0.41+/-0.3 and 0.22+/-0.1 mm, respectively. Gantry and couch isocentricities were 0.3+/-0.1 and 0.6+/-0.15 mm, respectively. The system overall RMS values were 0.9 and 0.6 mm with and without the couch errors included, respectively (isocenter variations due to couch rotation are microadjusted between couch positions). The positional verification of the marker was within 0.7+/-0.1 mm of the highest optical density on the radiochromic film, correlating well with the system's overall RMS value. The overall mean system deviation was 0.32+/-0.42 mm. CONCLUSIONS: The highest spatial errors were caused by image fusion and gantry rotation. A comprehensive quality-assurance program was developed for the authors' stereotactic radiosurgery program that includes medical imaging, linear accelerator mechanical isocentricity, and treatment delivery. For a successful treatment of trigeminal neuralgia with a 4-mm cone, the overall RMS value of equal to or less than 1 mm must be guaranteed.

Equipment Design↗
PubMed2003

Characterization of QTLs for harvest index and source-sink characters in a DH population of rice (Oryza sativa L.).

A DH population containing 81 DH lines from an indica-japonica cross of rice and an RFLP linkage map consisting of 232 markers were used to map quantitative trait loci(QTLs) for harvest index, biomass, grain yield, sink capacity and plant height by a computer program QTLMapper1.0 based on mixed linear models. A total of 21 significant main-effect QTLs and 9 pairs of epistatic loci were detected. Of these, three detected QTLs for grain yield collectively accounted for 42% of the phenotypic variation with a LOD of 7.10. These three grain yield QTLs were corresponded either to QTLs for harvest index or QTLs for biomass in both locations and directions of additive effects, which sheds light on the genetic basis of the formula 'grain yield = biomass x harvest index'. Four detected QTLs for harvest index collectively explained 46% of the total phenotypic variation and four QTLs for biomass jointly accounted for 64% of the trait variation. No coincidence of harvest index QTLs with any biomass QTLs was found, therefore indicating the possibility of pyramiding favorable alleles for both traits through gene recombination so as to obtain a genotype possessing both high harvest index and heavy plant biomass. Five QTLs for plant height were detected that cumulatively explained 64% of the phenotypic variation with a LOD of 11.62. Among these, three with smaller effects respectively co-located with some of the QTLs for biomass, sink capacity and/or grain yield, but not with any of harvest index QTLs, thus suggesting that plant height was to some extent directly associated with 'source' and 'sink' but not with 'transportation' of the 'source-transportation-sink' concept, at least in this genetic background and environment. In view of a somewhat low resolution of the genetic map used in the study and the fact that when plant height QTLs co-located with those for yield and/or yield related traits, these co-located QTLs were all in the same directions of additive effects, it is more likely that these QTLs co-located in a same chromosomal region might be a single QTL which have effects on multiple traits. If this is true, the above observation have led us to assume that QTLs which have pleotropic effects on yield and/or yield related traits and plant height are very different from those which had relatively large effects only on plant height. The former contribute strongly to yield and/or yield related traits but weakly to plant height while the later contribute mainly to plant height. Obviously, due to that an increase of plant height is always coupled with an increase in lodging susceptibility, discriminating between above two types of QTLs is critical in breaking the traits' undesired association in breeding for improved yield potential of rice. In addition, based on the co-location analysis of main-effect QTLs for the studied traits, five genomic regions were found to be highly associated with harvest index, biomass, sink capacity and grain yield.

Biomass↗
PubMed1998

[The high resolution spectroscopy of CH35 Cl3 and CH35Cl2(37) V = 3 stretching overtone].

The Fourier transform spectrometer (FTS) is used to record the high resolution spectrum of V = 3 stretching overtone for two isotopic species: CH35Cl3 and CH35Cl2(37)Cl. The rotational constants of CH35Cl2(37) Cl are calculated approximately from its isotope, CH35Cl3. The ground states combination difference method is used to assign the observed transitions. Because of the relatively small rotational constant, the resolution of 0.02 cm(-1) is still not enough to resolve the rotational K structure of CHCl3. So, all the observed transitions are assigned as parallel band transitions arising from the k = 0 rotational states. A weighted non-linear least-square fitting program is developed to fit the assigned transitions and derive the rotational constants. The result of the fitting for the CH35Cl2(37)Cl spectrum indicates that it is reasonable and reliable to derive the spectroscopic parameters using the isotopic effect.

English Abstract↗
PubMed1991

[Individual choice of ribonuclease and fluorofur doses in the treatment of patients with acute pancreatitis].

A method is suggested for individual calculation of optimal doses of ribonuclease and fluorofur on the basis of a standardized index--the degree of severity. A CM 1404 computer was used in solving the problem. From analysis of 500 case records by means of programs of discriminant and multidimensional linear regressive analysis a mathematical dependence was found between some parameters indirectly reflecting the severity of the patient's condition, the ribonuclease dose, and the efficacy of the treatment. A similar dependence for fluorofur was also studied. The discovered statistical regularity was realized as a nomogram for calculating the degree of severity and individual optimal doses of ribonuclease and fluorofur. The method was used in 114 patients. All the compared indices were found to be better than those in the group of patients for whom the dose of the agents (ribonuclease) was calculated on the basis of a constant dose per kg weight.

Acute Disease↗