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Neural responses to velocity gradients in macaque cortical area MT.

Visual motion, i.e. the pattern of changes on the retinae caused by the motion of objects or the observer through the environment, contains important cues for the accurate perception of the three-dimensional layout of the visual scene. In this study, we investigate if neurons in the visual system, specifically in area MT of the macaque monkey, are able to differentiate between various velocity gradients. Our stimuli were random dot patterns designed to eliminate stimulus variables other than the orientation of a velocity gradient. We develop a stimulus space ("deformation space") that allows us to easily parameterize our stimuli. We demonstrate that a substantial proportion of MT cells show tuned responses to our various velocity gradients, often exceeding the response evoked by an optimized flat velocity profile. This suggests that MT cells are able to represent complex aspects of the visual environment and that their properties make them well suited as building blocks for the complex receptive field properties encountered in higher areas, such as area MST to which many cells in area MT project.

Animals↗

Confirmation of location of epidural catheters by epidural pressure waveform and computed tomography cathetergram.

OBJECTIVE: Epidural pressure has remained a relatively unused test of physiological monitoring for the past 3 decades. It is our hypothesis that epidural pressure waveforms (EPWFs) obtained by transducing an epidural catheter (EC) can be used as a surrogate for the accurate location of the EC. The goal of this study was to validate this new method by comparing it with a more objective radiographic technique such as computed tomography cathetergram (CTC). METHODS: The EPWF and CTC were studied in 13 patients receiving continuous epidural analgesia (12 patients who had postoperative pain and 1 patient who had chronic pain). Of these 13 patients, 8 patients had reported inadequate analgesia, and 5 had reported satisfactory analgesia. First, the end of the EC was connected to a disposable pressure transducer, this was followed by a 5-mL normal saline bolus injection to ensure the patency of the EC, and the EPWF was recorded. Next, the patient was taken to an imaging suite and, after injecting contrast through the EC, the course of the catheter was imaged with computed tomography (CT). The CT images were studied by the neuroradiologist and correlated with the EPWF. RESULTS: The EPWF of 5 patients with clinically adequate analgesia revealed a pulsatile waveform on transducing the EC and a crescentic spread of contrast in the epidural space on CTC. In 8 patients with inadequate epidural analgesia, the EPWF measurement failed to show oscillations, and contrast collections were observed in the paraspinous muscles. The results of EPWF and CTC were compared using Fisher's exact test. CONCLUSIONS: The strong relationship between EPWF and CTC suggests that EPWF can be used reliably to confirm the correct placement of the EC in a selected group of patients.

Aged↗

A unified formalism using effective surface permittivity to study acoustic waves in various anisotropic and piezoelectric multilayers.

A unified formalism is presented that uses the effective surface permittivity (ESP) to study surface acoustic waves (SAW) in layered substrates and guided waves in layered plates. Based on known mathematical tools, such as ordinary differential equation and transfer matrix, a generalized surface impedance (GSI) concept is developed and exploited to investigate the acoustic propagation in various anisotropic and piezoelectric layered structures. The ESP function, originally defined for the surface of a homogeneous and semi-infinite piezoelectric substrate, is extended to both the top surface of and an interface in a layered half space, as well as to either surface of a finite-thickness plate. General ESP expressions for all mentioned configurations are derived in terms of an equivalent GSI matrix. It is shown that, when using the appropriate GSI matrices, the same form of the ESP expressions applies no matter whether the structure is a homogeneous half space alone or coated with a layered plate or a layered plate alone. GSI matrices are explicitly given in terms of the bulk partial mode solutions for a substrate and via the transfer matrix for a plate. Modified GSI matrices for structures consisting of both a plate and a substrate are also specified. Analytical development is fully detailed to suit program implementation. To illustrate its versatility, the formalism is also applied to two-substrate configurations, allowing one to analyze guided waves in a plate sandwiched between and interfacial waves existing along the boundary of two different media. Numerical examples are given to illustrate the spectrum features that the ESP shows for various structures. Deduced ESP expressions allow one to locate directly all piezoelectrically active waves in any structure including at least one piezoelectric layer. Acoustic modes that are not piezoelectrically active and those in non-piezoelectric materials can be also obtained by using the intermediate results, such as derived GSI matrices.

Journal Article↗

Profiled support vector machines for antisense oligonucleotide efficacy prediction.

BACKGROUND: This paper presents the use of Support Vector Machines (SVMs) for prediction and analysis of antisense oligonucleotide (AO) efficacy. The collected database comprises 315 AO molecules including 68 features each, inducing a problem well-suited to SVMs. The task of feature selection is crucial given the presence of noisy or redundant features, and the well-known problem of the curse of dimensionality. We propose a two-stage strategy to develop an optimal model: (1) feature selection using correlation analysis, mutual information, and SVM-based recursive feature elimination (SVM-RFE), and (2) AO prediction using standard and profiled SVM formulations. A profiled SVM gives different weights to different parts of the training data to focus the training on the most important regions. RESULTS: In the first stage, the SVM-RFE technique was most efficient and robust in the presence of low number of samples and high input space dimension. This method yielded an optimal subset of 14 representative features, which were all related to energy and sequence motifs. The second stage evaluated the performance of the predictors (overall correlation coefficient between observed and predicted efficacy, r; mean error, ME; and root-mean-square-error, RMSE) using 8-fold and minus-one-RNA cross-validation methods. The profiled SVM produced the best results (r = 0.44, ME = 0.022, and RMSE= 0.278) and predicted high (>75% inhibition of gene expression) and low efficacy (<25%) AOs with a success rate of 83.3% and 82.9%, respectively, which is better than by previous approaches. A web server for AO prediction is available online at http://aosvm.cgb.ki.se/. CONCLUSIONS: The SVM approach is well suited to the AO prediction problem, and yields a prediction accuracy superior to previous methods. The profiled SVM was found to perform better than the standard SVM, suggesting that it could lead to improvements in other prediction problems as well.

Databases, Genetic↗

Tris(tert-butoxy)siloxy derivatives of boron, including the boronous acid HOB[OSi(O(t)Bu)(3)](2) and the metal (siloxy)boryloxide complex Cp(2)Zr(Me)OB[OSi(O(t)Bu)(3)](2): a remarkable crystal structure with 18 independent molecules in its asymmetric unit.

Silanolysis of B(O(t)Bu)(3) with 2 and 3 equiv of HOSi(O(t)Bu)(3) led to the formation of (t)BuOB[OSi(O(t)Bu)(3)](2) (1) and B[OSi(O(t)Bu)(3)](3) (2), respectively. Compounds 1 and 2 are efficient single-source molecular precursors to B/Si/O materials via thermolytic routes in nonpolar media, as demonstrated by the generation of BO(1.5).2SiO(2) (BOSi2(xg)) and BO(1.5).3SiO(2) (BOSi3(xg)) xerogels, respectively. Use of a block copolymer template provided B/Si/O materials (BOSi2(epe) and BOSi3(epe)) with a broad distribution of mesopores (by N(2) porosimetry) and smaller, more uniform particle sizes (by TEM) as compared to the nontemplated materials. Hydrolyses of 1 and 2 with excess H(2)O resulted in formation of the expected amounts of (t)BuOH and HOSi(O(t)Bu)(3); however, reaction of 1 with 1 equiv of H(2)O led to isolation of the new boronous acid HOB[OSi(O(t)Bu)(3)](2) (3). This ligand precursor is well suited for the synthesis of new metal (siloxy)boryloxide complexes via proton-transfer reactions involving the BOH group. The reaction of 3 with Cp(2)ZrMe(2) resulted in formation of Cp(2)Zr(Me)OB[OSi(O(t)Bu)(3)](2) (4) in high yield. This rare example of a transition metal boryloxide complex crystallizes in the triclinic space group Ponemacr; and exhibits a crystal structure with an unprecedented number of independent molecules in its asymmetric unit (i.e., Z' = 18 and Z = 36). This unusual crystal structure presented an opportunity to perform statistical analyses of the metric parameters for the 18 crystallographically independent molecules. Complex 4 readily converts to Cp(2)Zr[OSi(O(t)Bu)(3)](2) (5) upon thermolysis or upon dissolution in Et(2)O at room temperature.

Journal Article↗

Fault-tolerant pedigree reconstruction from pairwise kinship relations.

MOTIVATION: Pedigrees reconstructed from biologically related ancient genomes have revealed many insights into (pre)history. To our knowledge, all reported ancient pedigrees have been primarily manually reconstructed, as existing pedigree reconstruction methods are ill-suited for the quality and nature of ancient DNA data. RESULTS: We introduce repare, an open-source software method to automatically reconstruct pedigrees from inferred pairwise kinship relations, which are readily obtainable from ancient genomes. This method reconstructs pedigrees by iteratively incorporating pairwise kinship relations into a set of candidate pedigrees, with pruning and sampling to reduce its search space. It optionally considers supporting information such as haplogroups and skeletal age-at-death estimates. We evaluate this method on a variety of simulated pedigrees with varying error rates and missingness. We also use this method to reconstruct several published pedigrees that were originally manually reconstructed; for one, we present a potential alternative topology. repare optionally incorporates user-inferred pedigree constraints, enabling "human-in-the-loop" reconstruction workflows. Especially when used with these user-inferred constraints, we find that repare represents a powerful and flexible tool for ancient pedigree reconstruction. AVAILABILITY AND IMPLEMENTATION: repare is freely available at https://github.com/Narasimhan-Lab/repare. In addition, source code, benchmark scripts, and benchmark results used in this work are archived at https://doi.org/10.5281/zenodo.19716772.

Pedigree↗

Crystallization and preliminary X-ray analysis of a quadruple mutant of staphylococcal nuclease.

A quadruple mutant of staphylococcal nuclease, nuclease (V66L/G79S/G88V/L108V), has been crystallized in a form well suited to moderate-to-high resolution x-ray diffraction analysis. This mutant is highly unstable; only about 20% of the protein in solution at room temperature is in its folded form. Under the crystallization conditions, the protein exhibits circular dichroism properties similar to, but not identical with, those of native wild type protein. The crystals belong to the space group P6(1)22 or P6(5)22 with unit cell dimensions of a = b = 61.1 A, c = 170.1 A and diffract to at least 2.5 A resolution. A data set complete to 3.7 A resolution has been collected and processed; attempts to determine the structure using molecular replacement techniques are under way.

Circular Dichroism↗

A direct approach to the study of the effect of gravity on axis formation in birds.

A system has been developed to enable the normal development of aborted very early uterine avian embryos, outside the female's uterus. The shell-less aborted egg was put into a foster shell of a sister egg, previously laid by the same female. The empty space between the shell and aborted egg was filled with artificial uterine fluid. The reconstructed eggs were incubated at 42 degrees C for 30 hours in a vertical position. The atmosphere contained a high concentration of CO2 (8-10%). At the termination of the 30 h the eggs were transferred to incubation at 37 degrees C in normal atmospheric conditions. Normal development has been recorded for a certain percentage of eggs incubated up to 12 days. In other cases abnormalities, arrested development or development of extraembryonic membranes only, without a sign of an embryonic axis, have been observed. The three important conclusions from the above experiments were: 1. It is possible to develop a closed, self-contained system, disconnected from the female's body, that would support the development of early uterine embryos. 2. The incidence of embryo-less extraembryonic membranes in such a system, is correlated with the degree of detachment of the "yolk" from the outer envelopes. 3. Such a system can be further developed into an experiment suited for microgravity conditions which will be an alternative to an experiment with live birds. The experiment will be aimed at testing the importance of gravity in changing the radially symmetrical avian blastoderm into a bilaterally symmetrical blastoderm.

Animals↗

Decompressive procedures. Indications and techniques.

Hemilaminectomy and dorsal laminectomy are the surgical techniques most suited for decompression of the thoracic, thoracolumbar, lumbar, and lumbosacral spine. Hemilaminectomy is preferred for decompressing the spinal cord before applying fixation devices for fractures/luxations. Dorsal laminectomy is the method of choice for exploration of the spinal canal and for decompression of the lumbosacral region. Either method is applicable to removal of herniated intervertebral disc material and fenestration of other disc spaces.

Animals↗

Determining the effective dimensionality of the genetic variance-covariance matrix.

Determining the dimensionality of G provides an important perspective on the genetic basis of a multivariate suite of traits. Since the introduction of Fisher's geometric model, the number of genetically independent traits underlying a set of functionally related phenotypic traits has been recognized as an important factor influencing the response to selection. Here, we show how the effective dimensionality of G can be established, using a method for the determination of the dimensionality of the effect space from a multivariate general linear model introduced by Amemiya (1985). We compare this approach with two other available methods, factor-analytic modeling and bootstrapping, using a half-sib experiment that estimated G for eight cuticular hydrocarbons of Drosophila serrata. In our example, eight pheromone traits were shown to be adequately represented by only two underlying genetic dimensions by Amemiya's approach and factor-analytic modeling of the covariance structure at the sire level. In contrast, bootstrapping identified four dimensions with significant genetic variance. A simulation study indicated that while the performance of Amemiya's method was more sensitive to power constraints, it performed as well or better than factor-analytic modeling in correctly identifying the original genetic dimensions at moderate to high levels of heritability. The bootstrap approach consistently overestimated the number of dimensions in all cases and performed less well than Amemiya's method at subspace recovery.

Animals↗

Percutaneous vertebroplasty in the management of osteoporotic vertebral compression fractures: initial experience.

INTRODUCTION: Vertebral compression fractures related to osteoporosis may cause persistent pain which impairs mobility and reduces the quality of life. Percutaneous vertebroplasty is a therapeutic interventional radiology procedure which is used in the management of pain relief in such fractures. It involves the injection of bone cement [polymethylmethacrylate (PMMA)] into the collapsed vertebrae under radiological guidance. This provides pain relief as well as increases the strength and stability of the vertebra. MATERIALS AND METHODS: A total of 16 patients with 17 osteoporotic compression fractures which were treated with percutaneous vertebroplasty over an 18-month period were studied. There were all women with the exception of 1 male patient. Their ages ranged from 61 to 87 years. The fracture sites were at the thoracolumbar junction from T12 to L3 levels. The majority of cases only required a unipedicular injection, with bipedicular injections in 3 cases. All cases were performed in the angiographic suite in the radiology departments, with biplanar fluoroscopy in one hospital. PMMA was injected in a semi-solid state under radiological guidance and screening into the collapsed vertebrae. RESULTS: All cases showed good technical success with no mortality or major complications. Only 2 cases had minor complications of cement leakage into the soft tissues of the back and adjacent disc space, respectively. There was sufficient pain relief in all patients and they were well enough to be discharged within 1 to 5 days after the procedure. Patients were followed up to evaluate the degree of long-term pain relief as well as analgesic usage. CONCLUSION: Percutaneous vertebroplasty is a new and minimally-invasive modality of treating pain in patients with osteoporotic compression fractures who are refractory to medical therapy. Under adequate imaging guidance, the risks of complications are minimal while the potential benefit to patients and their care-givers are significant.

Aged↗

[Comparative anatomical studies on the Jacobson organs of Nycticebus coucang Boddaert, 1785 (Prosimiae, Lorisidae) and Galago crassicaudatus E. Geoffroy, 1812 (Prosimiae, Lorisidae). I. Nycticebus coucang].

The goal of this research was to study the macroscopic and microscopic anatomy of the vomeronasal organ in Nycticebus coucang. Based on numerous measurements in cross-sections of all parts of the organ, three-dimensional graphs of the vomeronasal cartilage, the organ and the system of blood-vessels, situated around the organ, were drawn. Nycticebus has a well developed vomeronasal organ exhibiting a well developed sensory epithelium. The oral end of the organ opens into the middle part of the nasopalatine duct, which has an open connection with the cavum nasi and the cavum oris. The cartilago paraseptalis is connected with the cartilago ductus nasopalatini by the sickle-shaped part of the cartilago paraseptalis. An "outer bar", which is present in the vomeronasal cartilage of Tupaia, is absent in Nycticebus. The oral part of the organ contains nonciliated, pseudostratified epithelium with secretory crypts and goblet cells. In the main part of the organ the dorso-lateral wall consists of nonsensory, nonciliated, pseudostratified epithelium, while the sensory epithelium is situated in the dorsolateral wall. Serous glands, which are situated dorsal to the organ, open into the organ at its dorsal margin. Caudal to this part there is a long part of the organ without sensory epithelium. At its caudal end the organ is branched. The sensory epithelium of the vomeronasal organ is thicker than the sensory epithelium of the nose. It contains a nucleus-free space between the nuclei of supporting cells and the nuclei of sensory cells. The sensory epithelium contains about 92 000 receptor cells/mm2. Capillaries could not be seen in the epithelia of the organ. The vessels, which accompany the organ, are veins and capillaries. The dorsal veins exhibit thicker walls and a wider lumen than the ventral ones and are therefore better suited for the pumping-mechanism, as suggested by BROMAN (1920). Connective tissue, surrounding the organ, aids the pumping-mechanism of the veins.

Animals↗

Explorotory study of proton radiation therapy using large field techniques and fractionated dose schedules.

Three patients have been treated with 160-MeV protons combined with high-energy photons to examine the advantages and difficulties associated with the clinical implementation of a program of large-field, fractionated-dose, protonradiation therapy. We havefound it necessary to 1) obtain an accurate three-dimensional determination of the treatment volume including the density of all tissues in the beam path; 2) construct an adequate bolus to compensate for tissue heterogeneities; 3) use much more precise and accurate immobilization and patient positioning devices than used in photon irradiation; 4) treat with both protons and photons so as to keep the skin dose within an acceptable level. IN TISSUES WITHOUT SIGNIFICANT INHOMOGENETIES DUE TO BONE AND AIR SPACES WE HAVE DELIVEREDA WELL-DEFINED DOSE TO INVOLVED TISSUES WHILE SPARING DISTAL SENSITIVE STRUCTURES. However, in those regions where there is much "fine structure" of tissue density, it has been difficult to compensate satisfactorily for the inhomogeneties.

Adult↗

Radial maze type as a determinant of the choice behavior of rats.

Spatial memory of rats was examined in two types of radial mazes in which animals had to obtain food from 6-, 8-, or 12-different arms without repeating choices. In Maze 1 with tubular channels closed at the far end rats returned to the central platform by backing out from the just visited alley. In Maze 2 the tubular channels were equipped with one-way doors at both ends and the central platform was raised 5 cm above the floor. Rats leaving the far end of the alley returned to the central platform through a circular hole in its center. Performance was almost perfect in both apparatuses, but rats preferred to enter adjacent alleys in Maze 1 and widely separated alleys in Maze 2. These behaviors were significantly different from computer-simulated random choice from the set of correct solutions of the task. It is concluded that Maze 2 is better suited for repeated experiments with the same animal because the obligatory return to the center of the platform precludes the simplification of the task by response chaining.

Animals↗

Virtual reality for orthognathic surgery: the augmented reality environment concept.

PURPOSE: The objective of this study was to apply virtual reality technology to osteotomies of the facial skeleton. MATERIALS AND METHODS: Augmented reality can be considered a hybrid of virtual and real environment spaces, which are coregistered and simultaneously visualized. Using a see-through HMD (head-mounted display) and Interventional Video Tomography intraoperatively, partial visual immersion into a patient-related virtual data space augments the surgeon's perception as shown in an experimental study and clinical applications. RESULTS: Without limiting the surgical judgment, offering continuous observation of the operating field, the presented technology additionally provides visual access to invisible data of anatomy, physiology, and function and thus guarantees unencumbered and fluent surgery. CONCLUSION: Despite current shortcomings, augmented reality technology proved to be particularly well suited for use in osteotomies of the facial skeleton.

Anatomy, Cross-Sectional↗

Synthetic antibodies from a four-amino-acid code: a dominant role for tyrosine in antigen recognition.

Antigen-binding fragments (Fabs) with synthetic antigen-binding sites were isolated from phage-displayed libraries with restricted complementarity-determining region (CDR) diversity. Libraries were constructed such that solvent-accessible CDR positions were randomized with a degenerate codon that encoded for only four amino acids (tyrosine, alanine, aspartate, and serine). Nonetheless, high-affinity Fabs (K(d) = 2-10 nM) were isolated against human vascular endothelial growth factor (hVEGF), and the crystal structures were determined for two distinct Fab-hVEGF complexes. The structures revealed that antigen recognition was mediated primarily by tyrosine side chains, which accounted for 71% of the Fab surface area that became buried upon binding to hVEGF. In contrast, aspartate residues within the CDRs were almost entirely excluded from the binding interface. Alanine and serine residues did not make many direct contacts with antigen, but they allowed for space and conformational flexibility and thus played an auxiliary role in facilitating productive contacts between tyrosine and antigen. Tyrosine side chains were capable of mediating most of the contacts necessary for high-affinity antigen recognition, and, thus, it seems likely that the overabundance of tyrosine in natural antigen-binding sites is a consequence of the side chain being particularly well suited for making productive contacts with antigen. The findings shed light on the basic principles governing the evolution of natural immune repertoires and should also aid the development of improved synthetic antibody libraries.

Amino Acid Sequence↗

Applying futuristic technology to the priorities of the past.

The hot topic in health care executive suites across the nation is outcomes management: measuring the effects of interventions on the quality of life of patients. The halls of our institutions are buzzing about the shifting focus from the board room to the bedside, and from the balance sheet to the patient's chart. Is outcomes management just another fad that will result in an additional layer of space-age overhead with little relevance to our patients' goals? Aren't we already concerned enough about our patients? What happened to the old saw, "If it ain't broke, don't fix it?"

Outcome and Process Assessment, Health Care↗