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PubMed2002

Design of binary long-period fiber grating filters by the inverse-scattering method with genetic algorithm optimization.

An approach is presented to the design of binary long-period fiber grating (LPFG) filters based on the Gel'fand-Levitan-Marchenko (GLM) inverse-scattering method and genetic algorithm optimization. The nonuniform coupling strength of the binary grating can be realized by varying the local duty ratio. A coupled-mode theory combined with the Poisson sum formula for treating the binary index perturbation is developed for the application of the GLM synthesis method. Since the coupled-mode theory, which smears out the discrete coupling nature, can be regarded only as an approximation to the modeling of a binary LPFG, we use instead the transfer-matrix model to analyze the coupling behavior of a nonuniform binary LPFG. Based on the synthesized grating patterns from the GLM method, a real-coded genetic algorithm with the transfer-matrix model is used to compensate for the discrepancies resulting from use of the coupled-mode theory and to optimize the design. We exemplify the above procedure by designing a flatband LPFG filter and a high-visibility all-fiber Mach-Zehnder filter.

Journal Article↗
PubMed1979

Electrocardiographic changes resembling myocardial ischaemia in asymptomatic men with normal coronary arteriograms.

T wave and ST segment abnormalities in 20 asymptomatic men aged 18 to 55 were investigated because they were identical with myocardial ischaemic changes, and the professional livelihood of the subjects was jeopardised. Coronary arteriograms showed unobstructed arteries in all except one in whom a 50 per cent lesion of the left anterior descending artery was present. Left ventricular angiograms showed a normal contraction pattern, Ejection fractions were normal in 12 and increased in 8. Three characteristic electrocardiographic patterns were observed: flat or inverted T waves in leads II, III, aVF, and V4 to 6 designated type 1; deep T inversion particularly evident in leads V2 to 5 designated type 2, and minor ST segment depression in the inferior and lateral leads without T changes designated type 3. Characteristically, type 1 changes were temporarily suppressed by either beta-blockade or an overnight rest and were more abnormal in the standing position. Type 2 and 3 changes were relatively uninfluenced by these manoeuvres. Maximal treadmill exercise tests were positive in 6 and borderline or negative in 14. When repeated after oxprenolol all tests were negative. Echocardiograms showed asymmetric septal hypertrophy in 3 subjects (ratio of greater than 1.5 between ventricular septum and posterior left ventricular wall). After normalisation by an overnight rest, type 1 T wave abnormalities were reproduced by intravenous adrenaline infusion (0.024 to 0.18 microgram/kg/min) but not by noradrenaline or by adrenaline after prior administration of oxprenolol. When the T waves had remained deeply inverted before infusion despite rest (type 2) adrenaline infusion normalised them and again noradrenaline was without effect. This effect was also prevented by oxprenolol. Type 3 changes were uninfluenced by catecholamine infusion. Plasma catecholamine estimations suggest that catecholamine hypersecretion and hypersensitivity may both be relevant, particularly the latter. The apparent bimodal response of the ventricular myocardium to adrenaline infusion is not surprising since in vitro experiments suggest that reversal of T wave polarity in either direction may result from summation of changes in action potential duration in different parts of the heart. Such changes may be unimodal, that is both areas involved show lengthening or shortening of action potential duration, but by occurring at different rates may lead to a bimodal change in the differences in duration which generate the T wave.

Adolescent↗
PubMed1995

Complete sequence of a mariner transposable element from the predatory mite Metaseiulus occidentalis isolated by an inverse PCR approach.

Degenerate primers designed and synthesized based on two conserved regions of the mariner transposase open reading frame were used to amplify a 454 bp DNA fragment from M. occidentalis. Two inverse primers were then synthesized and used to amplify flanking genomic DNA fragments from M. occidentalis by a ligation-mediated inverse PCR. The complete mariner element (Moc1) was 1284 bp long, including the imperfect 28 bp inverted terminal repeat sequences, and shared 59% similarity to an active 1286 bp long D. mauritiana mariner element (Mos1). Insertions, deletions and substitutions were observed in the Moc1 sequence at several positions. No intact open reading frame was detected and the Moc1 element is considered inactive. Stringent Southern blot hybridizations revealed at least twelve copies of mariner sequences similar to Moc1 in the colonies tested.

Animals↗
PubMedDate not supplied

Stability of the braced ankle. A biomechanical investigation.

We measured the bare ankle and the braced angle-torque relationships in 12 uninjured volunteers under static and dynamic conditions within the full range of inversion motion. These relationships were measured with a specially designed mechanical device that allowed inversion movements with angular velocities up to 850 deg/sec. In testing the bare ankle under static conditions, the torque showed a 10-fold increase within the full range of motion (average, from 0.9 N-m at 7 degrees to about 8 N-m at 48 degrees of inversion). The slope of the angle-torque relationship increased under dynamic conditions giving higher torque values (up to 18 N-m on average). Both orthoses induced similar additional torques that increased linearly, up to about 6 N-m at 45 degrees, with higher angles of inversion. These additional torques are small compared with the amount of stress applied to the foot during a typical ankle sprain situation, such as recovering from a jump. Therefore, we propose that orthotic devices increase the ankle torque, counteracting the inversion movement, and also prevent the start of the inversion movement by preloading and maintaining the ankle in a proper anatomic position with optimal contact between the articular surfaces.

Acceleration↗
PubMedDate not supplied

Efficient algorithms for protein sequence design and the analysis of certain evolutionary fitness landscapes.

Protein sequence design is a natural inverse problem to protein structure prediction: given a target structure in three dimensions, we wish to design an amino acid sequence that is likely fold to it. A model of Sun, Brem, Chan, and Dill casts this problem as an optimization on a space of sequences of hydrophobic (H) and polar (P) monomers; the goal is to find a sequence that achieves a dense hydrophobic core with few solvent-exposed hydrophobic residues. Sun et al. developed a heuristic method to search the space of sequences, without a guarantee of optimality or near-optimality; Hart subsequently raised the computational tractability of constructing an optimal sequence in this model as an open question. Here we resolve this question by providing an efficient algorithm to construct optimal sequences; our algorithm has a polynomial running time, and performs very efficiently in practice. We illustrate the implementation of our method on structures drawn from the Protein Data Bank. We also consider extensions of the model to larger amino acid alphabets, as a way to overcome the limitations of the binary H/P alphabet. We show that for a natural class of arbitrarily large alphabets, it remains possible to design optimal sequences efficiently. Finally, we analyze some of the consequences of this sequence design model for the study of evolutionary fitness landscapes. A given target structure may have many sequences that are optimal in the model of Sun et al.; following a notion raised by the work of J. Maynard Smith, we can ask whether these optimal sequences are "connected" by successive point mutations. We provide a polynomial-time algorithm to decide this connectedness property, relative to a given target structure. We develop the algorithm by first solving an analogous problem expressed in terms of submodular functions, a fundamental object of study in combinatorial optimization.

Algorithms↗
PubMed2006

Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery.

The concept of constitutively active G-protein-coupled receptors is now firmly rooted in receptor pharmacology. Many independent research groups have contributed to its acceptance since its introduction by Costa and Herz in 1989. This concept necessitated a revised ligand classification, and a new category of inverse agonists was introduced alongside existing agonist and antagonist ligands. Initially, it was hoped that new therapeutic modalities would become available. However, the drug industry has not adopted inverse agonism as a design criterion and instead accepted that some compounds emerge as (neutral) antagonists in compound screening, whereas other compounds possess inverse agonistic activity. In this article, we summarize aspects of the impact of constitutive activity on the drug-discovery process: for example, its use in orphan receptor assays, its link with pharmacogenetics and genomics, and its relevance for currently marketed drugs.

Alternative Splicing↗
PubMed2004

Design of short fiber Bragg gratings by use of optimization.

We demonstrate an optimization approach for designing fiber Bragg gratings. A layer-peeling inverse-scattering algorithm is used to produce an initial solution, which is optimized numerically with an iterative optimization method. To avoid problems with local minima, we use merit functions that are zero for wavelengths for which the predefined demands (acceptance limits) are fulfilled, making it possible to alter the local minima under the optimization process without disturbing the global minimum. Because short gratings are difficult to design with inverse scattering, and because the time consume of the optimization increases rapidly with the grating length, the method is particularly useful for designing short gratings. The method is also useful when the demands are complex and difficult to handle with inverse-scattering methods. Design examples are given, including a dispersionless bandpass filter suitable for dense wavelength-division multiplexing and a filter with linear reflectivity.

Journal Article↗
PubMed2005

The preferred conformation of the tripeptide Ala-Phe-Ala in water is an inverse gamma-turn: implications for protein folding and drug design.

Recent studies have provided evidence that peptides as short as tripeptides do adopt preferred conformations. Here we report that the tripeptide Ala-Phe-Ala (AFA) in aqueous solution preferentially forms an inverse gamma-turn. Circular dichroism (CD) indicated the presence of a predominant turn structure, and Fourier transform infrared (FTIR) bands suggested the presence of a gamma-turn forming a bifurcated H-bond with the solvent molecules. The high-resolution structure was obtained by a combined use of NMR spectroscopy and calculations. On the basis of 30 unambiguous ROESY-derived distance restraints (including the Halpha-NH NOE between Ala(1) and Ala(3) and a hydrogen bond between the CO group of Ala(1) and the NH group of Ala(3)), calculations clearly demonstrated the presence of an inverse gamma-turn centered on Phe(2). From NOE data, we estimated a mole fraction for the gamma-turn of 0.65. Since for AFA an extended beta-strand was also reported [Eker, F., Griebenow, K., Cao, X., Nafie, L. A., and Schweitzer-Stenner, R. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 10054-10059], we investigated the possibility that gamma-turn and beta-strand may represent two major conformations. By using a best-fit procedure that calculated experimental NOEs as weighted averages of the effects originating from both structures, we were able to calculate with good accuracy the backbone NOEs at 280 K in terms of the two limiting conformers, yielding a mole fraction for the gamma-turn and beta-strand conformations of 0.60 and 0.40, respectively, in good agreement with those found by NOE data. The implication of the existence of a preferred conformation by a small structural element is discussed in the context of the nucleation of protein folding events and the design of small peptide and peptidomimetic drugs.

Alanine↗
PubMed2001

Neural-network compensation methods for capacitive micromachined accelerometers for use in telecare medicine.

Transducers represent a key component of medical instrumentation systems. In this paper, sensors that perform the task of measuring the physical quantity of acceleration are discussed. These sensors are of special significance since, by integrating their output signal, accelerometers can additionally provide a measure of velocity and position. Applications for such measurements and, thus, of accelerometers, range from early diagnosis procedures for tremor-related diseases (e.g., Parkinson's) to monitoring daily patterns of patient activity using telemetry systems. The system-level requirements in such applications are considered and two novel neural-network transducer designs developed by the authors are presented, which aim to satisfy such requirements. Both designs are based on a micromachined sensing element with capacitive signal pickoff. The first is an open-loop design utilizing a direct-inverse-control strategy, while the second is a closed-loop design, where electrostatic actuation is used as a form of feedback. Both transducers are nonlinearly compensated, capable of self-test, and provide digital outputs.

Acceleration↗
PubMed1996

Sample size for the exact conditional test under inverse sampling.

Inverse sampling is a sampling design in which one continues sampling subjects until one obtains a predetermined number of index subjects. This paper derives a procedure for calculation of the minimum required number of index subjects on the basis of the exact conditional test under inverse sampling. This paper studies quantitatively the effect on power calculations of the number of index subjects. To facilitate use of inverse sampling in study designs, this paper further provides a table that summarizes, in a variety of situations, the minimum required number of index subjects for powers equal to 0.90 and 0.80 at 0.05-level. It also includes a discussion on use of the approximation sample size formula derived on the basis of a variance-stabilizing transformation and large sample theory.

Analysis of Variance↗
PubMed2003

Design of artificial nucleobases for the recognition of the AT inversion by triple-helix forming oligonucleotides: a structure-stability relationship study and neighbour bases effect.

We report herein on the synthesis, the incorporation into triplex forming oligonucleotides (TFO) and the recognition properties of a series of synthetic nucleosides designed for the specific recognition of an inverted A x T base pair in a pyrimidine triple helix motif. These analogues were designed on the basis of the results obtained with our previously reported compounds S and B(t), in order to define a structure-stability relationship. We report also on the chemical nature effect of the bases flanking S in the case of S-containing TFOs, in order to get further informations about the recognition process within the A x TxS triplet. This study establishes guidelines for the conception of more potent analogues for the recognition of both A x T and G x C inverted base pairs.

Adenine↗
PubMed2005

Errors in two-point sound reproduction.

This paper deals with the problem of reproducing two signals at two points in space by using two acoustic sources. While much is now known about the techniques available for the design of matrices of inverse filters that enable this objective to be achieved in practice, it is still the basic physics of the sound field produced that controls the effectiveness of such systems and which ultimately dictates their design. The basic physical processes involved in producing the cross-talk cancellation that enables the reproduction of the desired signals is revisited here by using a simple two source/two field point free field model. The singular value decomposition is used to identify those frequencies where the inversion problem becomes ill-conditioned and to explain physically the origin of the ill-conditioning. As observed previously, it is found that cross-talk cancellation becomes problematic when the path length difference between the two sources and one of the field points becomes equal to one half the acoustic wavelength. The ill-conditioned frequencies are also found to be associated with a limited spatial region of cross-talk cancellation and with large source outputs manifested in the time domain by responses of long duration.

Acoustics↗
PubMed1999

Configural errors on WISC-III block design.

This study describes two experiments undertaken to explore the clinical significance and cognitive substrates of Block Design broken configurations in children. Broken configurations were defined as instances in which the child placed a block outside the 2 x 2 or 3 x 3 square matrix. In Experiment 1, 336 normal children between the ages of 6 and 14 were administered WISC-III Block Design. Broken configurations were fairly common, but almost always self-corrected. The tendency to break configurations was inversely related to overall Block Design performance and mother's level of education, and directly related to the perceptual cohesiveness of the design. In Experiment 2, children were administered WISC-III Block Design and a global-local similarity judgment task. The frequency of broken configurations was inversely related to global perceptual bias. Taken together, the results of these experiments indicate that while broken configurations are common, particularly on designs with high perceptual cohesiveness, a high number of broken configurations or final answers containing broken configuration are associated with weaker visuospatial skills. Broken configurations are also made more frequently by children whose perception is less influenced by the global properties of spatial stimuli.

Adolescent↗
PubMed2000

Increase in spinal canal area after inverse laminoplasty: an anatomical study.

STUDY DESIGN: In vitro measurement of the area of the spinal canal in the rostral and caudal portions of lumbar vertebrae before and after application of a new technique called "inverse laminoplasty." OBJECTIVES: To quantify the normal area of the spinal canal in the rostral and caudal portions of lumbar vertebrae and the amount of enlargement gained after inverse laminoplasty. SUMMARY AND BACKGROUND DATA: Other types of laminoplasty have been proven to increase the area of the spinal canal. Inverse laminoplasty has been performed in 10 patients but has not been evaluated in vitro. METHODS: The transverse and anteroposterior diameter of the spinal canal was measured in 34 vertebrae from seven cadavers using digital calipers. In each vertebra, the laminae and spinous process were removed en bloc using a high-speed drill. The removed piece was inverted and reattached with titanium mini-plates. The area of the spinal canal was again measured and compared with the prelaminoplasty measurements using paired Student's t tests. RESULTS: The anteroposterior diameter and area of the spinal canal were significantly smaller before surgery in the rostral than in the caudal part of the vertebrae (P <10(-3)). The rostral and caudal areas of the spinal canal increased by 61% and 17%, respectively, after the laminae were inverted (P <10(-3)). CONCLUSION: Because inverse laminoplasty is simple and increases the area of the spinal canal, it may prove to be a useful surgical technique for the treatment of lumbar spinal stenosis. Further studies are needed to determine whether the technique is biomechanically sound and whether it helps prevent perineural scarring.

Adult↗
PubMed2004

Acute puerperal uterine inversion.

OBJECTIVE: To determine the frequency, causes, clinical presentations, management and maternal mortality associated with acute puerperal inversion of the uterus. DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: The Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, over eight years period from 1st January 1995 to 31st December 2002. MATERIALS AND METHODS: All the patients who developed acute puerperal inversion of the uterus either in or outside the JPMC were included in the study. Patients of chronic uterine inversion were not included in the present study. Abdominal and vaginal examination was done to confirm and classify inversion into first, second or third degrees. RESULTS: 57036 deliveries and 36 acute uterine inversions occurred during the study period, so the frequency of uterine inversion was 1 in 1584 deliveries. Mismanagement of third stage of labour was responsible for uterine inversion in 75% of patients. Majority of the patients presented with shock, either hypovolemic (69%) or neurogenic (13%) in origin. Manual replacement of the uterus under general anaesthesia with 2% halothane was successfully done in 35 patients (97.5%). Abdominal hysterectomy was done in only one patient. There were three maternal deaths due to inversion. CONCLUSION: Proper education and training regarding placental delivery, diagnosis and management of uterine inversion must be imparted to the maternity care providers especially to traditional birth attendants and family physicians to prevent this potentially life-threatening condition.

Acute Disease↗
PubMed2002

Improved recognition of native-like protein structures using a family of designed sequences.

The goal of the inverse protein folding problem is to identify amino acid sequences that stabilize a given target protein conformation. Methods that attempt to solve this problem have proven useful for protein sequence design. Here we show that the same methods can provide valuable information for protein fold recognition and for ab initio protein structure prediction. We present a measure of the compatibility of a test sequence with a target model structure, based on computational protein design. The model structure is used as input to design a family of low free energy sequences, and these sequences are compared with the test sequence by using a metric in sequence space based on nearest-neighbor connectivity. We find that this measure is able to recognize the native fold of a myoglobin sequence among different globin folds. It is also powerful enough to recognize near-native protein structures among non-native models.

Amino Acid Sequence↗