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PubMedDate not supplied

An anytime local-to-global optimization algorithm for protein threading in theta (m2ñ2) space.

This paper describes a novel anytime branch-and-bound or best-first threading search algorithm for gapped block protein sequence-structure alignment with general sequence residue pair interactions. The new algorithm (1) returns a good approximate answer quickly, (2) iteratively improves that answer to the global optimum if allowed more time, (3) eventually produces a proof that the final answer found is indeed the global optimum, and (4) always terminates correctly within a bounded number of steps if allowed sufficient space and time. It runs in polynomial space, which is asymptotically dominated by the theta(m2ñ2) space required by the lower bound computation. Using previously published data sets and the Bryant-Lawrence (1993) objective function, the algorithm found the true (proven) global optimum in less than 5 min in all search spaces size 10(25) or smaller (sequences to 478 residues), and a putative (not guaranteed) optimum in less than 5 hr in all search spaces size 10(60) or smaller (sequences to 793 residues, cores to 42 secondary structure segments). The threading in the largest case studied was eventually proven to be globally optimal; the corresponding search speed in that case was the equivalent of 1.5 x 10(56) threadings/sec, a speed-up exceeding 10(25) over previously published batch branch-and-bound speeds, and exceeding 10(50) over previously published exhaustive search speeds, using the same objective function and threading paradigm. Implementation-independent measures of search efficiency are defined for equivalent branching factor, depth, and probability of success per draw; empirical data on these measures are given. The general approach should apply to other alignment methodologies and search methods that use a divide-and-conquer strategy.

Algorithms↗
PubMed2002

Euclidian space and grouping of biological objects.

MOTIVATION: Biological objects tend to cluster into discrete groups. Objects within a group typically possess similar properties. It is important to have fast and efficient tools for grouping objects that result in biologically meaningful clusters. Protein sequences reflect biological diversity and offer an extraordinary variety of objects for polishing clustering strategies. Grouping of sequences should reflect their evolutionary history and their functional properties. Visualization of relationships between sequences is of no less importance. Tree-building methods are typically used for such visualization. An alternative concept to visualization is a multidimensional sequence space. In this space, proteins are defined as points and distances between the points reflect the relationships between the proteins. Such a space can also be a basis for model-based clustering strategies that typically produce results correlating better with biological properties of proteins. RESULTS: We developed an approach to classification of biological objects that combines evolutionary measures of their similarity with a model-based clustering procedure. We apply the methodology to amino acid sequences. On the first step, given a multiple sequence alignment, we estimate evolutionary distances between proteins measured in expected numbers of amino acid substitutions per site. These distances are additive and are suitable for evolutionary tree reconstruction. On the second step, we find the best fit approximation of the evolutionary distances by Euclidian distances and thus represent each protein by a point in a multidimensional space. The Euclidian space may be projected in two or three dimensions and the projections can be used to visualize relationships between proteins. On the third step, we find a non-parametric estimate of the probability density of the points and cluster the points that belong to the same local maximum of this density in a group. The number of groups is controlled by a sigma-parameter that determines the shape of the density estimate and the number of maxima in it. The grouping procedure outperforms commonly used methods such as UPGMA and single linkage clustering.

Algorithms↗
PubMed2004

Omic space: coordinate-based integration and analysis of genomic phenomic interactions.

MOTIVATION: With the recent progress in genomics, various data sets of omic interactions describing networks of omic elements have become available. In order to obtain reliable hypotheses from the data, it is effective to integrate interactions from different sorts of data sets. In order to facilitate a coordinate-based integration and analysis of omic interactions, we introduce the concept of an omic space comprising a comprehensive set of omic planes. Genomic, transcriptomic, proteomic, metabolomic, phenomic and other omic planes are defined by two orthogonal genomic-coordinate axes. RESULTS: We show that the omic space concept helps us to assimilate biological findings comprehensively into hypotheses or models combining higher-order phenomena and lower-order mechanisms by demonstrating that a comprehensive ranking of correspondences among interactions in the space can be used effectively for estimating candidates of responsible gene pairs for epistatic interacting loci of tumors in mice. We also show that the omic space offers a convenient framework for database integration, by presenting a system named the 'Genome <==> Phenome Superhighway' (GPS) that serves as a framework for integration and visualization of omic interactions based on omic spaces of some model species including Homo sapiens, Mus musculus, Caenorhabditis elegans and Arabidopsis thaliana. AVAILABILITY: For the GPS web site, see http://omicspace.riken.jp/gps/.

Algorithms↗
PubMed2003

A neural basis for the perception of voices in external auditory space.

We used functional imaging of normal subjects to identify the neural substrate for the perception of voices in external auditory space. This fundamental process can be abnormal in psychosis, when voices that are not true external auditory objects (auditory verbal hallucinations) may appear to originate in external space. The perception of voices as objects in external space depends on filtering by the outer ear. Psychoses that distort this process involve the cerebral cortex. Functional magnetic resonance imaging was carried out on 12 normal subjects using an inside-the-scanner simulation of 'inside head' and 'outside head' voices in the form of typical auditory verbal hallucinations. Comparison between the brain activity associated with the two conditions allowed us to test the hypothesis that the perception of voices in external space ('outside head') is subserved by a temperoparietal network comprising association auditory cortex posterior to Heschl's gyrus [planum temporale (PT)] and inferior parietal lobule. Group analyses of response to 'outside head' versus 'inside head' voices showed significant activation solely in the left PT. This was demonstrated in three experiments in which the predominant lateralization of the stimulus was to the right, to the left or balanced. These findings suggest a critical involvement of the left PT in the perception of voices in external space that is not dependent on precise spatial location. Based on this, we suggest a model for the false perception of externally located auditory verbal hallucinations.

Acoustics↗
PubMed2004

The over-representation of contralateral space in parietal cortex: a positive image of directional motor components of neglect?

The activity of single cells was recorded in behaving monkeys while they performed several eye-hand directional motor tasks. The results revealed that in parietal area 7a there exists a directional representation of eye and hand motor space that, contrary to that of superior parietal, premotor and motor cortex, is highly skewed toward the contralateral workspace. In man, the loss of this representation after parietal lesions might explain the emergence of the directional movement disorders of neglect. In fact, although unilateral neglect is consequence of damage to different brain structures, it is more common and enduring after right inferior parietal cortex lesions. Neglect patients ignore and avoid interacting with events occurring in the contralesional part of their physical and mental space. Current theories distinguish perceptual from motor components of neglect. One key feature of the latter is directional hypokinesia, an impaired representation of space for action, evident as difficulty to plan hand movements toward the contralesional part of egocentric space. An impairment of a similar nature is also observed for eye movements. In this study, we offer an interpretation of directional movement disorders of neglect from a physiological perspective, i.e. by focusing on the mechanisms underlying the representation of visuomotor space in parietal cortex.

Animals↗
PubMed2001

C-SPACE (cleavage-specific amplification of cDNA ends): a novel method of ribozyme-mediated gene identification.

A hairpin ribozyme, RzCR2A, directed against position 323 of the hepatitis C virus 5'-untranslated region (HCV 5'-UTR) was used to establish and validate a novel method for the detection of cellular target molecules for hairpin ribozymes, termed C-SPACE (cleavage-specific amplification of cDNA ends). For C-SPACE, HeLa mRNA containing the transcript of interest was subjected to in vitro cleavage by RzCR2A in parallel with a control ribozyme, followed by reverse transcription using a modified SMART cDNA amplification method and cleavage-specific PCR analysis. C-SPACE allowed identification of the RzCR2A target transcript from a mixture containing the entire cellular mRNA while only requiring knowledge of the ribozyme binding sequence for amplification. In a similar approach, C-SPACE was used successfully to identify human 20S proteasome alpha-subunit PSMA7 mRNA as the cellular target RNA of Rz3'X, a ribozyme originally designed to cleave the negative strand HCV 3'-UTR. Rz3'X was found to substantially inhibit HCV internal ribosome entry site (IRES) activity and PSMA7 was subsequently confirmed to be involved in HCV IRES-mediated translation. Thereby, C-SPACE was validated as a powerful tool to rapidly identify unknown target RNAs recognized and cleaved by hairpin ribozymes.

5' Untranslated Regions↗
PubMedDate not supplied

Effects of irrigation, spacing and fertilization on flowering and growth in young Alnus rubra.

Flowering and vegetative growth were assessed in 19 half-sib families of Alnus rubra Bong. planted in a replicated field trial near Olympia, Washington, USA. The trial consisted of three square spacings (0.5, 1.0 and 2.0 m), two irrigation regimes (low and high), and two fertilization treatments (0 and 300 kg P ha(-1)). Male and female flowers were surveyed in all plots for all families at plantation ages 4 and 5 years. Female strobili were surveyed for seven families in the 2-m spaced plots at plantation age 6 years. The percentage of trees flowering and the number of flowers per tree were always greatest, and height and diameter growth were always least, in the low-irrigation regime. Phosphorus fertilization had no effect on the percentage of trees flowering or on 5-year height or diameter growth; it had a positive but small effect on the number of female flowers per tree at age 5 years. Wider spacing resulted in larger trees, higher rates of flowering, and higher tree survival. Within each irrigation regime, the percentage of trees flowering increased as tree size increased. There was substantial variation in flowering among families, with positive but low correlations between tree size and flowering attributes. At ages 4 and 5 years, the ratio of number of trees flowering in the low-irrigation regime to number of trees flowering in the high-irrigation regime differed among families. By age 6 years, many more trees flowered than in previous years, and differences between irrigation regimes were reduced. Early growth rates were rapid and resulted in substantial crown recession and mortality in the closer spacings by age 5 years. We conclude that spacings less than 2 m should only be used in seed production areas if roguing can be done by age 2 to 3 years.

Journal Article↗
PubMed1995

Perivascular spaces in eccrine spiradenoma. A clue to its histological diagnosis.

Perivascular spaces were found to represent a useful histological clue to the diagnosis of eccrine spiradenoma. They were observed in eight of nine eccrine spiradenomas but not in syringomas, nodular basal cell carcinomas, or glomangiomas. Perivascular spaces in spiradenomas consisted of variably sized spaces around one or more central blood vessels, bordered at the periphery by a palisade of tumor cells and lined at both sides by basement membrane collagen type IV. Perivascular spaces contained variable numbers of T lymphocytes in all cases and could undergo fibrosis, cystic dilatation, or hyalinization. In analogy to similar structures in thymomas, we suggest that perivascular spaces in spiradenomas are involved in the traffic of lymphocytes toward the tumor.

Adenoma, Sweat Gland↗
PubMedDate not supplied

Release of the first web space with the "goalpost" procedure in pediatric burns.

First web-space contractures commonly occur in dorsal and palmar hand burns. Both abduction and extension limitations develop as a result of reduction in thumb motion. Optimal treatment of first web-space contractures should treat both abduction and extension deformities and should minimize the need for reoperation in growing children. Many techniques exist to manage web-space contractures. This article describes a long rectangular flap release ("goalpost" procedure) used to treat first web deformities in pediatric patients with burns. During the period 1987 through 1989, 31 first web-space releases were performed in 23 patients (mean age 9.2 years). The operations were performed a mean of 50 months after burn injury. No wound complications occurred and no patient required repeat operation in the follow-up period. Range of motion in abduction and extension was increased a mean of 10 degrees. The goalpost procedure is a highly acceptable alternative to standard web-space releases and offers advantages in its ability to treat both abduction and extension contractures.

Adolescent↗
PubMed2001

Post retention: the effect of sequence of post-space preparation, cementation time, and different sealers.

Many endodontic sealers contain constituents that have been shown to inhibit the polymerization of resin cements. This may be important when prefabricated posts are cemented at the same appointment as root canal obturation. This study evaluated the effects of cementing posts with a resin cement immediately or at a delayed time period after obturation using Roth's 801 Elite Grade or AH26 sealer cements. The contribution of mechanical post-space preparation was also assessed as a critical variable. One hundred twenty extracted canines were randomly divided into eight experimental groups. The variables evaluated were the order of post preparation (either before or after obturation), the type of sealer used, and the time of post cementation. All teeth received a stainless steel #6 Parapost XP cemented with a resin cement, Panavia 21. Each experimental group underwent tensile testing for retention using an Instron universal testing machine. For both sealers posts cemented in teeth in which the canal was obturated before post-space preparation and thus had sealer-contaminated dentin removed by the space preparation procedure had significantly higher retentive values than those obturated after post-space preparation in which contaminated dentin might remain. Sealer used and time of cementation had no specific effect on retention. Achieving a clean, "freshened" dentinal surface during mechanical post-space preparation seems to be a critical variable for post retention when a resin cement is used.

Analysis of Variance↗
PubMed1996

The strength of plate fixation in relation to the number and spacing of bone screws.

Our purpose was to study the relationship between the number of plate holes filled and the spacing between the screws and the resultant strength of plated constructs. Broad regular DC plates were anchored with 4.5-mm cortical screws to blocks of polyurethane foam. Six constructs were tested: (a) screws in holes 1, 2, and 3; (b) screws in holes 1 and 3; (c) screws in holes 1 and 4; (d) screws in holes 1 and 5; (e) screws in holes 1 and 6; (f) screws in holes 1, 3, and 5. The strength was quantified using a material-testing system. In cantilever and four-point bending, the constructs were loaded in both gap-closing and gap-opening modes. Screws in holes 1, 2, and 3 were tested against other constructs. For cantilever bending (gap opening and gap closing), construct (a) was stronger than construct (b), as strong as construct (c), but weaker than the constructs with more widely spaced screws (p < 0.0001). In terms of four-point bending, for gap opening, the standard fixation (construct (a) was stronger than construct (b) but weaker than the more widely spaced constructs. For gap closing, construct (a) was stronger than constructs (b) and (c) but weaker than the rest. Regardless of the spacing of screws and the plate length, strength in torsion was dependent on the number of screws securing the plate. In a laboratory fracture model of plate-bone constructs tested to failure by screw pullout, wider spacing of bone screws increases the bending strength of screw-plate fixation and can be more effective than increasing the number of screws. Torsional strength is independent of screw placement in plates of a given width and depends on the number of screws used.

Bone Plates↗
PubMed1996

Surgical anatomy of the anterior cervical spine: the disc space, vertebral artery, and associated bony structures.

OBJECTIVE: To elucidate the relationships between the neurovascular structures and surrounding bone, which are hidden from the surgeon by soft tissue, and to aid in avoiding nerve root and vertebral artery injury in anterior cervical spine surgery. METHODS: Using six cadaveric spines, we measured important landmarks on the anterior surface of the spine, the bony housing protecting the neurovascular structures in the lateral disc space, and the changes that occur during the discectomy with interbody distraction of the vertebral bodies. The measurements included the distance between the medial borders of the longus colli muscle at the level of each interspace; the width and height of each disc space at the midline; the width and height of the costal process; the distances between the cranial tip of the uncinate process (UP) and the vertebral body (VB) above and from the tip of the UP to the vertebral artery; the anteroposterior diameter or the extent of the disc spaces in the midline; the height at the midpoint of the distracted disc space; the UP-VB distance in distraction; and the width of the visible nerve root. RESULTS: The distance between the medial borders of the longus colli muscles increased in a rostral to caudal direction. The height of the UP was shortest at C4-C5 and greatest at C5-C6; the width was narrowest at C4-C5 and widest at C6-C7. The width of the costal process measured from the VB to the anterior tubercle was narrowest at C2-C3 and widest at C6-C7. The midpoint height of the costal process was smallest at C6-C7 and tallest at C4-C5 and C5-C6. The nondistracted UP-vertebral artery distance was the shortest at C2-C3 and longest at C4-C5. The nondistracted UP-VB distance averaged 1 mm at C2-C3 and C6-C7 and 1.5 mm at C4-C5. The height of the distracted disc space was shortest at C2-C3 and C6-C7. The UP-VB distance after distraction was greatest at C4-C5. Only at the C2-C3 interspace was the nerve always above the process. The vertebral artery entered the foramen transversarium of C6 in all the specimens. CONCLUSION: Although avoiding unfortunate injury is not always possible, understanding the locations and relations among the anatomic features is the only safeguard against unwarranted damage.

Aged↗
PubMed1999

Zygomatic-transmandibular approach for giant tumors of the infratemporal fossa and parapharyngeal space.

OBJECTIVE: The surgical anatomy of the infratemporal fossa and parapharyngeal space is often not properly understood by neurosurgeons, because these areas are more related to other medical disciplines. This article provides a detailed description of the infratemporal fossa and parapharyngeal space anatomy in cadaveric specimens and offers a neurosurgical perspective on a surgical approach that allows wide exposure and complete resection of giant tumors in this location. METHODS: Ten cadaveric specimens were prepared for anatomic study. Dissections were performed to emphasize the relationship between bone, muscles, and neurovascular structures and to simultaneously expose the middle cranial fossa, the infratemporal fossa, and the parapharyngeal space. Ten patients with giant lesions in these areas (with maximum tumor diameter >8 cm) were treated via this approach. RESULTS: The main obstacles to approaching the infratemporal fossa and the parapharyngeal space are the zygomatic arch, the parotid gland, the facial nerve, and the ascending ramus of the mandible. Thus, by combining a pterional-zygomatic craniotomy with transmandibular access, working up and down the parotid gland, the exposure is wider and safer. Among the 10 patients treated, tumors were totally resected in 7, subtotally resected in 2, and partially resected in 1. Morbidity was unremarkable, and, in 8 patients, clinical status improved dramatically. CONCLUSION: The zygomatic-transmandibular approach allows resection of giant lesions in the middle cranial base, when they are invading the infratemporal fossa and parapharyngeal space, with a low morbidity rate.

Adolescent↗
PubMed1996

Monobloc and facial bipartition osteotomies for reconstruction of craniofacial malformations: a study of extradural dead space and morbidity.

This study evaluated the presence of extradural dead space following a monobloc or facial bipartition osteotomy and examined its natural history and relationship to postoperative infection and the presence of a ventriculoperitoneal shunt at the time of osteotomy in a consecutive series of patients with craniofacial dysostosis, frontonasal dysplasia, midline cranio-orbital clefts, and orbital hypertelorism. Only patients followed for at least 1 year were included in the study (range 1.3 to 5.5 years). The 23 patients studied were divided into three groups: 10 patients (mean age 9 years) underwent a monobloc osteotomy with advancement, 7 (mean age 8 years) a facial bipartition osteotomy with advancement, and 6 (mean age 7 years) a facial bipartition osteotomy without advancement. Standard craniofacial computed tomographic (CT) scans were obtained for each patient early after surgery (within 2 weeks in 13 patients and at 6 to 8 weeks in 10 patients) and again 1 year after surgery in every case. The extradural dead space was measured from a reproducible axial CT scan slice for each patient at each postoperative interval. An initial dead space was documented in the retrofrontal region of the anterior cranial fossa when the reconstruction incorporated forward projection of the osteotomy parts. This space was found to be obliterated by the expanded brain by 6 to 8 weeks in the patients examined by CT scan slice for each patient at each postoperative in all patients. Perioperative complications also were documented. The presence of a ventriculoperitoneal shunt at the time of osteotomy (7 of 23 patients) did not increase the risk of complications or alter the pattern of dead space closure after operation. Two patients developed infectious complications that were managed without long-term consequences.

Adolescent↗
PubMed1999

Classification of the first web space free flap of the foot and its applications in reconstruction of the hand.

Owing to its unique anatomic arterial supply and dual nerve innervation, the first web space of the foot can be used to harvest various sizes and shapes of flaps, which the authors have classified into four types according to their usage in hand reconstruction. This in turn depends on the site, shape, and size of the soft-tissue defect in the hand. Web skin flaps (n = 8) were used in prevention of contracture in the first web space and for proximal finger reconstruction. Two-island skin flaps (n = 4) were used to resurface the pulp defect in two adjacent fingers. In severe adduction contracture of the first web space, fill-up web flaps (n = 10) were used to replace the volume defect after a release procedure in the hand. Adjuvant web flaps (n = 9) were used in wrap-around procedures, in dorsalis pedis flap transfer, and in vascularized joint transfer to supplement the main flaps and to restore sensation in the reconstructed area. In the past 10 years up to February of 1998, a total of 31 patients with soft-tissue defects in the hand and fingers were reconstructed using the web space free flap with flap survival rate of 100 percent. The mean static 2-point discrimination was 8.5 (7.2 to 10) mm, and the mean first web angle was 86 degrees. The advantage of the first web space flap from the foot is that it can easily be harvested to match various sizes and shapes of defects in the hand and fingers. In addition, because of the anatomic similarity in contour, thickness, texture, and nerve innervation with the hand, the sensory restoration is excellent with minimal morbidity at the donor site. By classifying the flaps into four types according to various sizes, shapes, and the site from which the flap are harvested, clinical usefulness in various types of hand and finger reconstruction was confirmed.

Adolescent↗
PubMed1994

Blood levels in macular cystoid spaces and their relationship to retinal vein obstruction.

BACKGROUND: Blood levels in macular cystoid spaces are commonly seen in patients with branch or central retinal vein obstruction, but have not been previously reported. METHODS: To determine blood levels in cystoid spaces, a retrospective study was conducted of 102 eyes with branch retinal vein obstruction, 54 eyes with central retinal vein obstruction, 207 eyes with clinically significant diabetic macular edema, and 109 eyes with aphakic or pseudophakic cystoid macular edema seen over a 5-year period. RESULTS: Definite blood levels in cystoid spaces were found in 26 eyes (25%) with branch vein obstruction and in 4 eyes (8%) with central vein obstruction. In contrast, this clinical change was detected in only 1 of 207 eyes (1%) with diabetic cystoid macular edema, and in only 2 of 109 eyes (2%) with aphakic or pseudophakic cystoid macular edema (P < 0.001). When blood levels in cystoid spaces were detected in patients with branch vein obstruction, the site of obstruction tended to be superotemporal (P < 0.05). CONCLUSION: Blood levels in cystoid spaces are an important sign of retinal vein obstruction, and may help establish the diagnosis in certain cases.

Adult↗
PubMed1989

Comparison of disc space heights after anterior lumbar interbody fusion.

Thirty-one consecutive patients underwent anterior interbody fusion of 40 levels of the lumbar spine using autogenous, autologous, or mixed iliac crest graft. Each patient's disc space height was measured preoperatively, immediately postoperatively, and an average of 29 months postoperatively. The immediate postoperative radiograph demonstrated an average increase in disc space height of 89%, or 9.5 mm for each operated level. The late radiographic evaluation, from 7 to 54 months postoperatively, showed an average decrease of 1%, or 0.1 mm for each level. At late follow-up, no correlation could be found between the time from the operation and disc space height. One hundred percent of patients developed disc space height decreases during the postoperative period, with 46% of levels being narrower than their preoperative height at last follow-up. Loss of distraction is a normal postoperative occurrence of the procedure. Disc space distraction is temporary with anterior interbody fusion.

Adult↗
PubMed1995

The role of distraction in improving the space available for the cord in cervical spondylosis.

STUDY DESIGN: This study analyzed the effects of distraction via strut graft insertion on the canal dimensions in spondylotic human cadaver cervical spines. Transverse and anteroposterior diameters and cross-sectional areas were measured by transverse computed tomography imaging before and after distraction without direct decompression. OBJECTIVES: This experiment was designed to address whether distraction across the disc space without direct canal decompression can improve the space available for the cord. SUMMARY OF BACKGROUND DATA: Smith-Robinson anterior discectomy and fusion have been shown to improve clinical symptoms of radiculopathy and myelopathy even in the absence of direct decompression. This has been postulated to be the result of gradual resorption of intruding osteophytes. However, the immediate effects of indirect distraction alone have not been previously investigated. METHODS: Four cadaver spines from elderly donors were harvested intact. The transverse diameter, anteroposterior diameter, and cross-sectional area of the spinal canal were measured before and after discectomy and distraction via insertion of fibular strut graft by digitization of contiguous computed tomography scan slices. RESULTS: The spinal canal dimensions before distraction were found to vary in a sinusoidal pattern around the disc space, with the maximum measurements located at the pedicle and the minimum measurements at the spondylotic ridge above or below the disc space. Distraction via strut graft insertion significantly increased the anteroposterior diameter and cross-sectional area, but had a negligible effect on transverse diameter. CONCLUSIONS: Anterior discectomy and distraction with a strut graft can significantly improve the space available for the cord in cervical spondylosis. Osteophyte debridement, which risks iatrogenic injury to the cord, may not always be necessary for improving clinical radiculopathy and myelopathy.

Aged↗