Computer-assisted stereotactic brain operations by means including computerized axial tomography.

With a computerized program system for stereotactic brain operations it becomes possible for the first time to react even before running a possible risk, e.g., in case of punctures in the midbrain, the brain stem, or in the hypothalamus, by simulating the operative procedure even before starting the operation itself. This is effected by the ability to change the penetration angle of the electrode or by choosing a different point of trepanation. The inclusion of computerized axial tomography, especially through the presentation of the CT scan, made to measure with the help of the linear transformation, and of the input of the cranial and ventricular coordinates through a digitizer, together with the coordinates resulting from the X-ray picture, brings the definition of the target point to a still greater optimum. Thus the safety and the precision of the stereotactic operation have been improved even further.     

X-ray and magnetic resonance stereotaxy for functional and nonfunctional neurosurgery

By means of new plastic stereotactic ring and head fixers, stereotactic procedures can be combined with MRI, with stereotactic coordinates obtained from the MRI images. The method was rechecked against CT stereotaxy and shows a good correspondence of the target coordinates. With MRI stereotaxy, structures near bony regions will be more accessible than with CT stereotaxy. Moreover, the MRI procedure seems to have advantages for functional therapy without the necessity of contrast ventriculography.     

A multipurpose CT-guided stereotactic instrument of simple design

The instrument is based upon a radiolucent ring fixed to the skull by four pins. This locks into a frame for CT scanning from which the x, y and z stereotactic coordinates are derived. The head ring may be locked into a compatible support on the operating table for biopsy. A similar support and localization system is used for rotational radiotherapy. With the current 14 MeV apparatus, fields as small as 2 cm in diameter are available with 90% dosage fall-off in the surrounding 1-cm shell.     

Analytically defined surfaces to analyze molecular interaction properties

Molecular surfaces are widely used for characterizing molecules and displaying and quantifying their interaction properties. Here we consider molecular surfaces defined as isocontours of a function (a sum of exponential functions centered on each atom) that approximately represents electron density. The smoothness is advantageous for surface mapping of molecular properties (e.g., electrostatic potential). By varying parameters, these surfaces can be constructed to represent the van der Waals or solvent-accessible surface of a molecular with any accuracy. We describe numerical algorithms to operate on the analytically defined surfaces. Two applications are considered: (1) We define and locate extremal points of molecular properties on the surfaces. The extremal points provide a compact representation of a property on a surface, obviating the necessity to compute values of the property on an array of surface points as is usually done; (2) a molecular surface patch or interface is projected onto a flat surface (by introducing curvilinear coordinates) with approximate conservation of area for analysis purposes. Applications to studies of protein-protein interactions are described.     

Brown-Roberts-Wells stereotactic frame modifications to accomplish magnetic resonance imaging guidance in three planes

The Brown-Roberts-Wells (BRW) computer tomography (CT) stereotactic guidance system has been modified to accommodate magnetic resonance imaging (MRI). A smaller head ring, which fits in standard MRI head coils, is constructed of a non-ferromagnetic aluminum ring that is split to prevent eddy currents and anodized to prevent MRI image distortion and resolution degradation. A new localizing device has been designed in a box configuration, which allows BRW stereotactic coordinates to be calculated from coronal and sagittal MRI images, in addition to axial images. The system was tested utilizing a phantom and T1- and T2-weighted images. Using 5-mm MRI scan slices, targets were localized accurately to a 5-mm cube in three combined planes. Optimized calibration of both low field strength (0.3 T) and high field strength (1.5 T) MRI systems is necessary to obtain thin slice (5 mm) images with acceptable image resolution. To date, 10 patients have had MRI stereotactic localization of brain lesions that were better defined by MRI than CT.     

Microcomputer stereotactic atlas

A stereotactic atlas to determine thalamic target sites has been incorporated into a microcomputer. Variability studies of the thalamus with mean and standard deviations of nuclear borders are depicted graphically for overlay onto operative images. Internal landmarks traditionally used to reference target points for functional stereotaxis may be determined by conventional ventriculography or derived from magnetic resonance scans. Modeling of polyline vertices established from gray scale contour mapping and atlas reconstructions further enhance the spatial understanding of relationships to midline structures. Computer integration of anatomic reference points, graphically depicted images and stereotactic atlas data into head frame coordinates can be accomplished. This method is consistent with established stereotactic techniques and allows the visual conceptualization of imaged and graphic data for functional stereotaxis.     

The role of computed tomographic and digital radiographic techniques in stereotactic procedures for electrode implantation and mapping, and lesion localization

This paper describes a computer-based system for analyzing stereotactic CT scans and angiograms. Simple Plexiglas frames containing metallic marker pellets and rods are affixed to the sides of the frame during CT scanning and angiography. The images of these markers are recognized by the computer program and used to compute the frame coordinate system. Coordinates of a lesion on CT and angiogram images may be readily computed and coordinate sets specified by the operator may be displayed on the imager, along with positions of implanted electrodes and a numerical indication of recorded activity for each site.     

The Promise of Intravaginal Rings for Prevention: User Perceptions of Biomechanical Properties and Implications for Prevention Product Development

Intravaginal rings (IVRs) are currently under investigation as devices for the delivery of agents to protect against the sexual transmission of HIV and STIs, as well as pregnancy. To assist product developers in creating highly acceptable rings, we sought to identify characteristics that intravaginal ring users consider when making decisions about ring use or non-use. We conducted four semi-structured focus groups with 21 women (aged 18–45) who reported using an IVR in the past 12 months. Participants manipulated four prototype rings in their hands, discussed ring materials, dimensionality, and “behavior,” and shared perceptions and appraisals. Five salient ring characteristics were identified: 1) appearance of the rings’ surfaces, 2) tactile sensations of the cylinder material, 3) materials properties, 4) diameter of the cylinder, and 5) ring circumference. Pliability (or flexibility) was generally considered the most important mechanical property. Several ring properties (e.g., porousness, dimensionality) were associated with perceptions of efficacy. Women also revealed user behaviors that may impact the effectiveness of certain drugs, such as removing, rinsing and re-inserting the ring while bathing, and removing the ring during sexual encounters. As product developers explore IVRs as prevention delivery systems, it is critical to balance product materials and dimensions with use parameters to optimize drug delivery and the user experience. It is also critical to consider how user behaviors (e.g., removing the ring) might impact drug delivery.     

Enantiomeric separation of tetrahydroisoquinoline alkaloids by high-performance liquid chromatography with β-cyclodextrin as chiral selector

Tetrahydroisoquinoline alkaloids, which are known to be present not only in plants but also in animals, including mammals, can be considered as condensation products of 2-phenylethylamines (e.g., catecholamines) with aldehydes (e.g., acetaldehyde) or 2-oxo acids (e.g., pyruvic acid). In this study the possibility of separating the optical isomers of several tetrahydroisoquinolines by high-performance liquid chromatography was investigated. For isosalsoline, tetrahydropapaveroline and laudanosoline a good enantiomeric separation could be achieved by applying β-cyclodextrin-bonded silica as stationary phase in connection with various mobile phases. With respect to laudanosoline, the addition of β-cyclodextrin as chiral selector to the mobile phase using a C₁₈ reversed-phase column as stationary phase revealed an even higher resolution when compared with the chiral columns. All tested tetrahydroisoquinolines which could be well separated into enantiomers bear a hydroxyl group at carbon atom 7 as a common structural feature. Those alkaloids substituted with a methoxy group on position 7 instead of a hydroxyl group (e.g., salsolidine) failed to be resolved into their optical isomers. Therefore, the presence of a hydroxyl group on C7 of the aromatic ring seems to be conducive to steric discrimination. However, the separation results for 1-carboxysalsolinol were unsatisfactory although this molecule possesses a 7-hydroxyl group. In this case the existence of a carboxyl group on C1 reduced the chiral recognition and thus the enantiomeric resolution. © 1995 Wiley-Liss, Inc.     

Lassitude: The emotion of being sick

Our long co-evolutionary history with infectious agents likely began soon after the rise of the first single-celled organisms. This ongoing evolutionary arms race has generated complex host adaptations, many highly conserved, for resisting infection (e.g., innate and acquired immune systems, infection-sensitive developmental programs, sexual reproduction). A large body of evidence suggests that, in humans, pathogen-avoidance disgust is an emotion that motivates avoidance of cues associated with pathogens, thereby reducing infection. However, the question of whether there is an emotion that coordinates resistance to active infection has received less attention. We propose that lassitude is such an emotion. It is triggered by cues of active infection and coordinates the fight against infection by: (a) reducing energetically expensive movement to make more energy available to the immune system, (b) reducing exposure to additional infections and injuries that would compound the immune system's workload, (c) promoting thermoregulatory behaviors that facilitate immunity, (d) regulating food consumption to be beneficial for the host but detrimental to pathogens, and (e) deploying strategies that elicit caregiving behavior from social allies. Lassitude exhibits the core features of an emotion – it is triggered by cues of an adaptive problem (i.e., infection), generates a characteristic facial expression (e.g., slack facial muscles, drooping eyelids, slightly parted lips), and has distinct qualia (e.g., profound tiredness, reduced appetite, feelings of vulnerability, altered temperature perception, increased pain sensitivity). We outline the information-processing structure of lassitude, review existing evidence, suggest directions for future research, and discuss implications of lassitude for models of human evolution.     

Optimization of the aromatase inhibitory activities of pyridylthiazole analogues of resveratrol

Aromatase is an established target not only for breast cancer chemotherapy, but also for breast cancer chemoprevention. The moderate and non-selective aromatase inhibitory activity of resveratrol (1) was improved about 100-fold by replacement of the ethylenic bridge with a thiadiazole and the phenyl rings with pyridines (e.g., compound 3). The aromatase inhibitory activity was enhanced over 6000-fold by using a 1,3-thiazole as the central ring and modifying the substituents on the 'A' ring to target the Met374 residue of aromatase. On the other hand, targeting the hydroxyl group of Thr310 by a hydrogen-bond acceptor on the 'B' ring did not improve the aromatase inhibitory activity.     

Conversion from a virtual-bond chain to a complete polypeptide backbone chain

A method for generating a complete polypeptide backbone structure from a set of C^α coordinates is presented. Initial trial values of ? and ψ for a selected residue are chosen (essentially from an identification of the conformational region of the virtual-bond backbone, e.g., and α-helical region), and values of ? and ψ for the remaining residues (both towards the N- and C-terminus) are then computed, subject to the constraint that the chain have the same virtual-bond angles and virtual-bond dihedral angles as the given set of C^α coordinates. The conversion from C^α coordinates to full backbone dihedral angles (?,ψ) involves the solution of a set of algebraic equations relating the virtual-bond angles and virtual-bond dihedral angles to standard peptide geometry and backbone dihedral angles. The procedure has been tested successfully on C^α coordinates taken from standard-geometry full-atom structures of bovine pancreatic trypsin inhibitor (BPTI). Some difficulty was encountered with error-sensitive residues, but on the whole the backbone generation was successful. Application of the method to C^α coordinates for BPTI derived from simplified model calculations (involving nonstandard geometry) showed that such coordinates may be inconsistent with the requirement that ?_Pro be near ?75°. In such a case, i.e., for residues for which the algebraic method failed, a leastsquares minimizer was then used in conjunction with the algebraic method; the mean-square deviation of the calculated C^α coordinates from the given ones was minimized by varying the backbone dihedral angles. Thus, these inconsistencies were circumvented and a full backbone structure whose C^α coordinates had an rms deviation of 0.26 Å from the given set of C^α coordinates was obtained.     

Stereotactic neurosurgery and computerized tomographic scanning

The marriage of computerized tomographic (CT) scanning and stereotactic surgery opens up new technical possibilities, as it becomes feasible to introduce a probe into any lesion which is identified on a CT scan. The various CT stereotactic techniques are reviewed, and generally involve four variations. The head holder of a standard stereotactic apparatus can be adapted to the CT scanner to interdigitate the coordinates of both devices in a known relationship. Second, some types of CT scanners allow the visualization of the vertical coordinate. Third, a stereotactic microdrive can be incorporated into the scanner. Finally, a simple aiming device can be attached to the patient's head and repeated scans taken as the probe is advanced to the target. Various authors have reported the use of techniques for biopsy, aspiration of cysts or hematomas, insertion of radioisotopes, or as an adjunct to open surgery.     

Ab initio molecular orbital calculations on furanose sugars: a study with the 6-31G basis set

Ab initio molecular orbital calculations were performed on 2-deoxy-beta-D-glycero-tetrofuranose (1) using the 6-31G* basis set to evaluate the effect of ring conformation on the molecular parameters (bond lengths, angles, and torsions). Geometric optimizations were conducted on the planar and ten envelope conformers of 1, and these data were compared to those obtained from previous calculations using the STO-3G and 3-21G basis sets. Conformational energy profiles derived from 3-21G and 6-31G* data were found to be qualitatively comparable. The effect of furanose ring conformation on key bond lengths (e.g., C-H, C-O), bond angles (e.g., COC), and bond torsions (e.g., the exoanomeric C-1-O-1 torsion) was examined, and a qualitative agreement was observed between the 3-21G and 6-31G* analyses. The results indicate that, for semi-quantitative ab initio studies of intact carbohydrates, the 3-21G basis set is sufficient, and that the STO-3G basis set should not be employed unless crude structural approximations are desired. The observed concerted behavior of C-O bond lengths in the vicinity of the anomeric carbon of the aldofuranose ring has suggested a possible role of C-1-O-1 bond orientation in affecting the mechanism of glycoside bond hydrolysis.     

A New Method for the Analysis of Soft Tissues with Data Acquired under Field Conditions

Analyzing soft-tissue structures is particularly challenging due to the lack of homologous landmarks that can be reliably identified across time and specimens. This is particularly true when data are to be collected under field conditions. Here, we present a method that combines photogrammetric techniques and geometric morphometrics methods (GMM) to quantify soft tissues for their subsequent volumetric analysis. We combine previously developed methods for landmark data acquisition and processing with a custom program for volumetric computations. Photogrammetric methods are a particularly powerful tool for field studies as they allow for image acquisition with minimal equipment requirements and for the acquisition of the spatial coordinates of points (anatomical landmarks or others) from these images. For our method, a limited number of homologous landmarks, i.e., points that can be found on any specimen independent of space and time, and further distinctive points, which may vary over time, space and subject, are identified on two-dimensional photographs and their three-dimensional coordinates estimated using photogrammetric methods. The three-dimensional configurations are oriented by the spatial principal components (PCs) of the homologous points. Crucially, this last step orients the configuration such that x and y-information (PC1 and PC2 coordinates) constitute an anatomically-defined plane with the z-values (PC3 coordinate) in the direction of interest for volume computation. The z-coordinates are then used to estimate the volume of the tissue. We validate our method using a physical, geometric model of known dimensions and physical (wax) models designed to approximate perineal swellings in female macaques. To demonstrate the usefulness and potential of our method, we use it to estimate the volumes of Barbary macaque sexual swellings recorded in the field with video images. By analyzing both the artificial data and real monkey swellings, we validate our method''s accuracy and illustrate its potential for application in important areas of biological research.     

The geometry of shape space: application to influenza

Shape space was proposed over 20 years ago as a conceptual formalism in which to represent antibody/antigen binding. It has since played a key role in computational immunology. Antigens and antibodies are considered to be points in an abstract "shape space", where coordinates of points in this space represent generalized physico-chemical properties associated with various (unspecified) physical properties related to binding, such as geometric shape, hydrophobicity, charge, etc. Distances in shape space between points representing antibodies and (the shape complement) of antigens are assumed to be related to their affinity, with small distances corresponding to high affinity. In this paper, we provide algorithms, related to metric and ordinal multidimensional scaling algorithms first developed in the mathematical psychology literature, which construct explicit, quantitative coordinates for points in shape space given experimental data such as hemagglutination inhibition assays, or other general affinity assays. Previously, such coordinates had been conceptual constructs and totally implicit. The dimension of shape space deduced from hemagglutination inhibition assays for influenza is low, approximately five dimensional.The deduction of the explicit geometry of shape space given experimental affinity data provides new ways to quantify the similarity of antibodies to antibodies, antigens to antigens, and the affinity of antigens to antibodies. This has potential utility in, e.g. strain selection decisions for annual influenza vaccines, among other applications. The analysis techniques presented here are not restricted to the analysis of antibody-antigen interactions and are generally applicable to affinity data resulting from binding assays.     

Single-scan stereotactic tumor biopsy and brachytherapy

Stereotactic tumor biopsy and brachytherapy catheter implantation can be accomplished with targets derived from computed axial tomography and magnetic resonance scans. Computer manipulation of image data allows both diagnostic and therapeutic procedures to be carried out from a single set of scan slices. This eliminates the need for repeat scanning as part of the surgical procedure. Microcomputer technology is sufficiently advanced to handle the images and graphics necessary for stereotactic neurosurgery. A system based on the IBM PC/AT designed for this purpose uses readily available graphics software and custom-designed imaging programs. Direct loading of computed axial or magnetic resonance scan images from magnetic tape can be accomplished. Determination of points, contours and volumes in three-dimensional space allows intraoperative alignment of image data and patient landmarks within the stereotactic head frame using pattern recognition overlays. Three-axis scaling for magnification correction along with rotational and linear data transformations provide the basis for single-scan stereotaxis. Interactive computer graphics integrate image, patient and frame coordinates for target determination. This method eliminates the need to design and fabricate nonmagnetic or radiolucent scanner-compatible devices.     

Himbacine derived thrombin receptor (PAR-1) antagonists: structure-activity relationship of the lactone ring

The structure-activity relationship (SAR) of the lactone ring of himbacine derived thrombin receptor (PAR-1) antagonists (e.g., 2-5) is described. The effect of the lactone carbonyl group on binding to PAR-1 is dependent on the substitution pattern of the pyridine ring. A stereoselective intramolecular Michael addition reaction to the vinyl pyridine group was observed for these pyridine analogs of himbacine in basic conditions at elevated temperature.