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PubMed2003

Haplotyping as perfect phylogeny: a direct approach.

A full haplotype map of the human genome will prove extremely valuable as it will be used in large-scale screens of populations to associate specific haplotypes with specific complex genetic-influenced diseases. A haplotype map project has been announced by NIH. The biological key to that project is the surprising fact that some human genomic DNA can be partitioned into long blocks where genetic recombination has been rare, leading to strikingly fewer distinct haplotypes in the population than previously expected (Helmuth, 2001; Daly et al., 2001; Stephens et al., 2001; Friss et al., 2001). In this paper we explore the algorithmic implications of the no-recombination in long blocks observation, for the problem of inferring haplotypes in populations. This assumption, together with the standard population-genetic assumption of infinite sites, motivates a model of haplotype evolution where the haplotypes in a population are assumed to evolve along a coalescent, which as a rooted tree is a perfect phylogeny. We consider the following algorithmic problem, called the perfect phylogeny haplotyping problem (PPH), which was introduced by Gusfield (2002) - given n genotypes of length m each, does there exist a set of at most 2n haplotypes such that each genotype is generated by a pair of haplotypes from this set, and such that this set can be derived on a perfect phylogeny? The approach taken by Gusfield (2002) to solve this problem reduces it to established, deep results and algorithms from matroid and graph theory. Although that reduction is quite simple and the resulting algorithm nearly optimal in speed, taken as a whole that approach is quite involved, and in particular, challenging to program. Moreover, anyone wishing to fully establish, by reading existing literature, the correctness of the entire algorithm would need to read several deep and difficult papers in graph and matroid theory. However, as stated by Gusfield (2002), many simplifications are possible and the list of "future work" in Gusfield (2002) began with the task of developing a simpler, more direct, yet still efficient algorithm. This paper accomplishes that goal, for both the rooted and unrooted PPH problems. It establishes a simple, easy-to-program, O(nm(2))-time algorithm that determines whether there is a PPH solution for input genotypes and produces a linear-space data structure to represent all of the solutions. The approach allows complete, self-contained proofs. In addition to algorithmic simplicity, the approach here makes the representation of all solutions more intuitive than in Gusfield (2002), and solves another goal from that paper, namely, to prove a nontrivial upper bound on the number of PPH solutions, showing that that number is vastly smaller than the number of haplotype solutions (each solution being a set of n pairs of haplotypes that can generate the genotypes) when the perfect phylogeny requirement is not imposed.

Algorithms↗

PubMed2003

Method for quantitatively assessing physical risk factors during variable noncyclic work.

OBJECTIVES: Assessing exposure to physical risk factors during variable noncyclic work can be problematic. The purpose of this study was to modify an existing data reduction method for directly quantifying physical exposures during variable noncyclic work. METHODS: Myoelectric activity of the finger flexors of two groups of workers, heavy equipment operators (N=25) and mechanics (N=25), was sampled to determine the intensity and duration of forceful exertions during normal tasks. Data were reduced with a modification of the exposure variation analysis (EVA), called clustered EVA (CEVA), using three intensity and two duration categories. A two-way, mixed-effects, repeated-measures analysis of variance evaluated the percentage of sampled work time in each CEVA category. RESULTS: CEVA was able to quantify variable noncyclic work, and it contrasted the work of the two groups, with simple effects significantly different for all the exposure categories. The mechanics performed high-intensity short-duration contractions 9.1% of the time, whereas the operators had similar contractions only 1.8% of the time. Conversely, the operators used low-intensity contractions of prolonged duration over 81% of the time, compared with only 43% for the mechanics. CONCLUSIONS: CEVA is a useful modification of EVA for contrasting the noncyclic work typical of understudied industries like construction. A simplification of electromyography with summary measures such as CEVA provides a comprehensible, yet accurate measure of forceful exertions during worktasks.

Adult↗

PubMed1978

[Levels of axial lesion in severe head injuries (author's transl)].

Over the past few years considerable amount of clinical syndromes describing brain stem levels of lesion were reported. This work was undertaken to establish, if possible, a simplification of criterions of axial lesions in head injuries. 125 patients with severe head injuries were strictly selected. Statistical analysis of careful examination of clinical pattern was performed and correlated, when possible, with anatomical lesions. Only four homogeneous groups were isolated:--group I represents the cortico-sub-cortical level,--group II représents the diencéphalie level,--group III represents the upper brain stem level with two subdivisions dependent upon the mechanism of herniation : central or uncus,--group IV represents the lower brain stem level.

Brain Stem↗

PubMed2000

Digital pulse processing: new possibilities in nuclear spectroscopy

Digital pulse processing is a signal processing technique in which detector (preamplifier output) signals are directly digitized and processed to extract quantities of interest. This approach has several significant advantages compared to traditional analog signal shaping. First, analyses can be developed which take pulse-by-pulse differences into account, as in making ballistic deficit compensations. Second, transient induced charge signals, which deposit no net charge on an electrode, can be analyzed to give, for example, information on the position of interaction within the detector. Third, deadtimes from transient overload signals are greatly reduced, from tens of micros to hundreds of ns. Fourth, signals are easily captured, so that more complex analyses can be postponed until the source event has been deemed "interesting". Fifth, signal capture and processing may easily be based on coincidence criteria between different detectors or different parts of the same detector. XIAs recently introduced CAMAC module, the DGF-4C, provides many of these features for four input channels, including two levels of digital processing and a FIFO for signal capture for each signal channel. The first level of digital processing is "immediate", taking place in a gate array at the 40 MHz digitization rate, and implements pulse detection, pileup inspection, trapezoidal energy filtering, and control of an external 25.6 micros long FIFO. The second level of digital processing is provided by a digital signal processor (DSP), where more complex algorithms can be implemented. To illustrate digital pulse processing's possibilities, we describe the application of the DGF-4C to a series of experiments. The first, for which the DGF was originally developed, involves locating gamma-ray interaction sites within large segmented Ge detectors. The goal of this work is to attain spatial resolutions of order 2 mm sigma within 70 mm x 90 mm detectors. We show how pulse shape analysis allows ballistic deficit to be significantly reduced in these detectors. A second experiment involves studying exotic nuclei by observing their 1 MeV direct proton decays following implantation in a Si crossed stripe detector at 35 MeV. Whereas the implantation paralyzes analog electronics for almost 10 micros, the DGF allows the study of decay times as short as 1 micros. Initial energy and time resolution results are presented. Finally, we show how the DGF's precise timing and coincidence capabilities lead to significant experimental simplifications in dealing with phoswich detectors, low background counting work, and trace Pb detection by coincident photon detection.

Journal Article↗

PubMed1990

[Outpatient hemorrhoidectomy using the CO2 laser].

In the free standing center of ambulatory surgery of Nice, proctology with carbon dioxide laser is a basic activity. Among 177 cases of proctology operated during 1989, we find 91 hemorroïdectomies realized with CO2 laser in strictly ambulatory surgery (no hospitalisation). This work's interet is demonstrating adaptation to the laser makes many advantages to the classic operation of Milligan and Morgan: simplification of the surgical technique easy post-operative course, no hospitalisation and quicker return to work, leading to a lower cost of this pathology. Complications are rare and excellent results noted.

Female↗

PubMed1999

Bacterivory rate estimates and fraction of active bacterivores in natural protist assemblages from aquatic systems

Unlike the fraction of active bacterioplankton, the fraction of active bacterivores (i.e., those involved in grazing) during a specified time period has not been studied yet. Fractions of protists actively involved in bacterivory were estimated assuming that the distributions of bacteria and fluorescently labeled bacteria (FLB) ingested by protists follow Poisson distributions. Estimates were compared with experimental data obtained from FLB uptake experiments. The percentages of protists with ingested FLB (experimental) and the estimates obtained from Poisson distributions were similar for both flagellates and ciliates. Thus, the fraction of protists actively grazing on natural bacteria during a given time period could be estimated. The fraction of protists with ingested bacteria depends on the incubation time and reaches a saturating value. Aquatic systems with very different characteristics were analyzed; estimates of the fraction of protists actively grazing on bacteria ranged from 7 to 100% in the studied samples. Some nanoflagellates appeared to be grazing on specific bacterial sizes. Evidence indicated that there was no discrimination for or against bacterial surrogates (i.e., FLB); also, bacteria were randomly encountered by bacterivorous protists during these short-term uptake experiments. These analyses made it possible to estimate the ingestion rates from FLB uptake experiments by counting the number of flagellates containing ingested FLB. These results represent the first reported estimates of active bacterivores in natural aquatic systems; also, a proposed protocol for estimating in situ ingestion rates by protists represents a significant improvement and simplification to the current protocol and avoids the tedious work of counting the number of ingested FLB per protist.

Journal Article↗

PubMed1999

Adaptation of the differential display RT-PCR technique to isolate sugarcane genes induced by plant association with endophytic nitrogen-fixing bacteria.

Differential Display RT-PCR is a powerful technique that has been used to isolate differentially expressed genes. This technique was first described by Liang & Pardee, in 1992. Afterwards, several modifications were introduced in the original version, including a simplification described by Sokolov & Prockop, in 1994. In this work, we describe an adaptation of the Sokolov & Prockop technique, in order to isolate sugarcane genes induced by plant association with endophytic nitrogen-fixing bacteria. Several modifications were introduced: the use of oligo-dT primer in the first strand cDNA synthesis, replicates of the PCR reactions, analysis of the amplified fragments on silver stained polyacrilamide gel and confirmation of cloning the differentially amplified selected band prior to its molecular characterisation. The methodology established was successfully used to identify a large number of differentially amplified sugarcane cDNAs. So far, one of these cDNAs was already isolated and characterized.

DNA, Complementary↗

PubMed1989

Assumptions of the QALY procedure.

The Quality Adjusted Life Year (QALY) has been proposed as a useful index for those managing the provision of health care because it enables the decision-maker to compare the 'value' of different health care programmes and in a way which, potentially at least, reflects social preferences about the appropriate pattern of provision. The index depends on a combination of a measure of morbidity and the risk of mortality. Methodological debate has tended to concentrate on the technicalities of producing a scale of health; and philosophical argument has concentrated on the ethics of interpersonal comparison. There is little recognition of the fragility of the theoretical assumptions underpinning the proposed combination of morbidity and risk of mortality. The context in which the proposed indices are being developed is examined in Section 2. Whilst most working in the field of health measurement eschew over-simplification, it is clear that the application of micro-economics to management is greatly facilitated if a single index can be agreed. The various approaches to combining morbidity and mortality are described in Section 3. The crucial assumptions concern the measurement and valuation of morbidity; the procedures used for scaling morbidity with mortality; and the role of risk. The nature of the valuations involved are examined in Section 4. It seems unlikely that they could ever be widely acceptable; the combination with death and perfect health poses particular problems; and aggregation across individuals compounds the problem. There are also several technical difficulties of scaling and of allowing for risk which have been discussed elsewhere and so are only considered briefly in Section 5 of this paper.(ABSTRACT TRUNCATED AT 250 WORDS)

Health↗

PubMed2004

Determination of cell capacitance using the exact empirical solution of partial differential Y/partial differential Cm and its phase angle.

Measures of membrane capacitance offer insight into a variety of cellular processes. Unfortunately, popular methodologies rely on model simplifications that sensitize them to interference from inevitable changes in resistive components of the traditional cell-clamp model. Here I report on a novel method to measure membrane capacitance that disposes of the usual simplifications and assumptions, yet is immune to such interference and works on the millisecond timescale. It is based on the exact empirical determination of the elusive partial derivative, partial differential Y/partial differential C(m), which heretofore had been approximated. Furthermore, I illustrate how this method extends to the vesicle fusion problem by permitting the determination of partial differential Y(v)/partial differential C(v), thereby providing estimates of fusion pore conductance and vesicle capacitance. Finally, I provide simulation examples and physiological examples of how the method can be used to study processes that are routinely interrogated by measures of membrane capacitance.

Algorithms↗

PubMed1975

[Research in antitumoral chemotherapy. X. Cytotoxic and antitumoral activity of beta-nitrostyrenes and of composed nitrovinyl derivatives].

In previous work the antitumoral cytotoxicity of beta-nitrostyrenes obtained by simplification of the aristolochic acid molecule was demonstrated. The effect of modifying the three characteristic parts of the beta-nitrostyrene molecule has now been investigated. The results obtained in vitro and in vivo allow hypothesis of a mechanism of action for the various beta-nitrostyrene and nitrovinyl compounds studied and definition of the maximum simplification compatible with retention of biological activity.

Animals↗

PubMedDate not supplied

Points for consideration: transferring and changing hospital clinical laboratories.

BACKGROUND: The laboratories of Carmel Medical Centre were located in the main hospital building since its establishment (1977). Due to expansion of the clinical wards, the laboratories were relocated to a nearby building. The project was utilized for reorganization of the laboratories. METHODS: The basic design addressed the existing hospital needs based mainly on the original organization of the laboratories. The project allowed for the prospective organizational changes. The planning, design, and erection were performed by teams of the hospital and by outside parties, headed by the hospital management and the laboratories' director. The laboratories' staff was involved in all phases of the project. RESULTS: The project laid the foundations for future consolidation, i.e., establishment of a central reception station and merging of chemistry, endocrinology, pharmacology, and segments of immunology. The merging involved performance but not validation of tests. Separation between research and routine work was achieved. By-products attained were as follows: simplification of tube handling, reduction in volume of blood needed, improvements in safety, employees' amenities, general atmosphere, and communication within personnel. CONCLUSION: The successful transfer resulted from appropriate design, close cooperation between management and personnel, and the ability to pinpoint problems at early stages with ad hoc solutions.

Hospital Design and Construction↗

PubMed1998

[Models of arterial pressure using a Windkessel type model: role of the functional arterial properties].

UNLABELLED: The Windkessel model is a linear model which does not take into account the structural and functional variations of the arteries related to the pulsatility of the blood pressure (BP) and its variations between systole and diastole. OBJECTIVE: To analyse the performance of a BP modelisation where the parameters of AC are adjusted in a dynamic fashion according to a curvilinear relationship of the arterial properties (compliance) in relationship to the BP between systole and diastole. DESIGN AND METHODS: 9 control subjects (age 25 +/- 3). The non invasive measures of the radial BP waveform (Millar tonometry) was compared to that constructed by an electric simulator reproducing the model in a sysmetrical network subdivised into 121 segments where we introduced for each subject: at cardiac level, the aortic stroke volume (Doppler echocardiography), and at the radial level, the dynamic values of compliance and diameter according to an arc-tangent model (measured by arterial echography NiUS02). RESULTS: The BP obtained by the adjusted model, where the AC parameter follows the curvilinear, relationship dV/dP measured experimentally, was not significantly different from the experimental, while in the constant model (AC at mean BP level) the systolic BP was different. CONCLUSION: This work shows in an experimental way the limits inherent in simplification in the Windkessel modelisation of the vascular system with constant parameters. It shows in a conduction artery the influence of the functional properties of the arterial wall on the level of systolic and diastolic BP.

Adult↗

PubMed1976

[The immunologic tumor diagnosis].

Issuing from a possibility of classification of tumour-associated antigens (TAA), corresponding to themodern state of recognition, the present situation of the immunological tumour diagnostics is discussed. The direct proof of tumour-associated antigens in the blood or in other body fluids, as one of the fundamental possibilities, is hitherto practically matured only for the alpha-fetoprotein and in this case only contribute to the diagnostics of liver carcinomas and malignant teratoblastomas. The determination of the carcinoembryonal antigen (CEA) in the serum or plasm has at present no essential diagnostic significance, may however, be used for the control of the therapeutic effect of cancer of the colon, rectum as well as the stomach. It is reserved for prospective studies to estimate the valency of the determination of CEA or fetal sulphoglycoproteid antigen in the gastric juice for the recognition of early carcinomas of the stomach. At present the proof of an immune response of the tumor carrier to TAA in vitro seems to be more favourable as a second way of the immunological tumour diagnostics. Sensitivity as well as specificity might here at first higher be estimated, when they are theoretically established. Whereas the inhibition test of leucocyte migration and technically similar variants in apparently sufficient specifity have an insufficient sensitivity and thus give too many falsely negative results the mobility test of the electrophoresis of macrophages in the modification of the immunological tumour profile distinguishes itself by a high certainty and by evidence on the probable localisation of the organ and the primary tumour (up to now verified for the cancer of colon and rectum, carcinomas of the stomach). Apart from the research of further principles, however, even for this test technological simplifications are to be found, before a broader use in routine work becomes practicable.

Antibodies, Neoplasm↗

PubMedDate not supplied

Simplification of immune adherence hemagglutination test for detection of rabies antibodies in human serum.

In the present work the immune adherence hemagglutination test (IAHA) was standardized in a simplified procedure. This test showed good reproducibility, better than the classical mice serum neutralization test (SN). The tests showed high correlation degree: high titers in one test corresponded to high titers in the other one, and the same occurred with low titers. The IAHA test is extremely simple, fast to perform, and of low cost when compared to tests such as SN or indirect immunofluorescence (IIF). It also proved to be useful in less sophisticated laboratories or even as a screening test for the titration of rabies antibodies.

Antibodies, Viral↗

PubMed1997

[The updated guideline 'Gastric complaints' o the Dutch College of General Practitioners; a reaction from a gastroenterologist].

This update has been well thought-out, and is a useful basis for further investigation in general practice. Further simplification may enhance its usefulness, however, e.g. by reducing the proposed three working diagnoses (aspecific gastric complaints, ulcer complaints, reflux complaints) to two: reflux complaints and gastric complaints. In addition, medication in the guideline might be restricted to acid inhibitory treatment and early serological determination of Helicobacter pylori infection might be included.

Gastroesophageal Reflux↗

PubMed1996

Capture and RT-PCR of hepatitis C virus RNA with safety primers.

The principle and practice of the polymerase chain reaction (PCR) has had a major impact on medical research. This is a powerful method but it does have its limitations, especially for clinical diagnostic work. We describe some improvements of hepatitis C virus (HCV) amplification such as simplification of specimen preparation, elimination of false negative reactions influenced by point mutations, and fluorimetric detection. The aim of the method is to make the procedure as easy and as inexpensive as possible for routine laboratories and for blood screening. After rapid chemical denaturation of the clinical specimen with guanidine thiocyanate and simultaneous hybridization of biotinylated primers to template HCV RNA, the product was fixed to streptavidin-coated magnetic beads and potential inhibitors were removed in easy washing steps. To eliminate the influence of point mutations within the primer binding sites, primer sets with different lengths at their 3'-end were developed for capture, reverse transcription, and amplification of genomic fragments by PCR. Positive results were identified by fluorescence staining. The low cost of the method allows the quantitation of templates by testing of dilution series as is common in microbiological laboratories.

DNA Primers↗

PubMed1998

Models of protein interactions: how to choose one.

BACKGROUND: There have been many attempts to approximate realistic protein interaction energies by coarse graining (i.e. considering interactions between amino acids rather than those between atoms). In particular, many 20-letter models have been derived (corresponding to the 20 naturally occurring amino acids). Because such models remain computationally infeasible, many two-letter models have been proposed as further simplifications. The choice of which model to use remains arbitrary, however. In this work, we formulate the framework within which the quality of approximate interaction potentials with respect to folding can be defined explicitly. RESULTS: Using a recently proposed criterion for comparing interaction matrices, we compare various 20 x 20 interaction matrices and obtain the two-letter model that most closely approximates each 20 x 20 matrix. We find that there are considerable differences among the 20 x 20 matrices. In particular, some matrices are much more similar to the hydrophobic model than others. Furthermore, we find that although the best two-letter approximation of a 20-letter model is a significantly better approximation than a random two-letter model, it is still a poor approximation of realistic protein interactions. CONCLUSIONS: The determination of the best two-letter approximations of various 20-letter models of protein interaction energies reveals the degree to which hydrophobic interactions dominate in each of the models and hence in proteins.

Models, Chemical↗

PubMed1990

An immunoenzymoassay for histamine.

The clinical diagnosis of allergies needs appropriate tools for the measurement of histamine release from leukocyte suspension of affected patients. In the last few years the established fluorometric procedure has been challenged by alternatives like histamine radioimmunoassays (RIA). Although measurements of histamine with the latter methods make this procedure more accessible as a diagnostic tool, further simplifications are always welcomed. A newly developed immunoenzymoassay for histamine is described in the present work and compared to a recent radioimmunoassay. Sensitivity and specificity are shown to be comparable in both procedures.

Acetylcholinesterase↗