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At least 217 records · Page 12Linked to original sources

The N-methyl-D-aspartate receptor inhibitory potencies of aromatic inhaled drugs of abuse: evidence for modulation by cation-pi interactions.

Benzene and several close structural analogs are inhaled drugs of abuse with general anesthetic activity. By virtue of their pi electron clouds, they may engage in attractive electrostatic interactions with cationic atomic charges on protein targets. In this study, we tested the hypothesis that inhaled drugs of abuse inhibit human N-methyl-D-aspartate (NMDA) receptors with potencies that correlate with their abilities to engage in cation-pi interactions. Electrophysiological techniques were used to define the NR1/NR2B NMDA receptor inhibitory concentrations of volatile benzene analogs, and computer modeling was used to quantify their abilities to engage in cation-pi interactions and their molecular volumes. In addition, each compound's octanol/gas partition coefficient (a measure of hydrophobicity) was quantified. All 18 compounds inhibited human NR1/NR2B NMDA receptors reversibly and in a concentration-dependent manner. NMDA receptor inhibitory potency correlated strongly with the ability to engage in cation-pi interactions, weakly with hydrophobicity, and was independent of molecular volume. This is consistent with the hypothesis that cation-pi interactions enhance the binding of inhaled drugs of abuse to the NMDA receptor and suggests that the receptor binding site(s) for these drugs possesses significant cationic character.

Animals↗

A graphic digital database of Drosophila embryogenesis.

Modern studies of the genetic control of development have increased the need for an accurate and comprehensive storage and display of gene expression data. This can be achieved in the form of an electronic graphic database of development. Here, we introduce the first steps towards a database of Drosophila embryogenesis. For each morphologically defined stage, a complete series of histological and/or optical sections are generated (optical sections are generated by laser confocal microscopy). Digitized sections are imported into a drawing program where they serve as templates to define the contours of organs and the position of individual cells. From these data, surface and point cloud models of all developmental stages are generated. Gene expression data can be entered by translating the expression domain of a given gene into the three-dimensional coordinate system of the database.

Analog-Digital Conversion↗

The large millimeter telescope/el Gran Telescopio Milimétrico: a new instrument for astrobiology.

The Instituto Nacional de Astrofísica, Optica y Electrónica in Mexico and the University of Massachusetts in the U.S.A. are collaborating to build the world's largest radio telescope that operates at short millimeter wavelengths. This facility, known as the Large Millimeter Telescope (LMT) or el Gran Telescopio Milimétrico (GTM), is being sited at an altitude of 4600 m on Volcan Sierra Negra in the Mexican state of Puebla. The telescope will be a fully steerable dish with a diameter of 50 m and a surface consisting of 180 panels that are actively adjusted under computer control to correct for deformations due to gravity and temperature gradients. Instruments will include focal plane arrays to image both continuum and spectral line emission from celestial sources. The LMT/GTM will be an extremely powerful facility for studies encompassing almost all areas of astronomy, including astrobiology. In particular, the high sensitivity, angular resolution, and mapping speed will enable detailed investigations of the organic chemistry of interstellar molecular clouds, protoplanetary disks, and comets.

Chemistry, Organic↗

A case of late-onset psychosis: integrating neuropsychological and SPECT data.

We report the case of a 67-year-old woman who experienced a sudden onset of psychotic illness (i.e., prominent delusions and hallucinations) that has endured for approximately 3 years. As part of her neurobehavioral work-up, a SPECT scan revealed right frontal and left anterior temporal-lobe hypoperfusion. Serial neuropsychological evaluations obtained 2 years apart demonstrated a steady decline on tests of executive control (monitoring, allocation of attention, perseveration) and visuospatial abilities, whereas performance in other areas of cognitive functioning have remained steady and in the normal range for the patient's age. Over this same period of time, serial EEG, MRI, and neurology examinations have been within normal limits. Thus, there was little evidence with which to diagnose dementia. It is suggested that concomitant impairment in executive control, coupled with a degraded capacity to process perceptual information, can give rise to enduring psychotic behavior.

Aged↗

Cytochrome b gene for species identification of the conservation animals.

A partial DNA sequence of cytochrome b gene was used to identify the remains of endangered animals and species endemic to Taiwan. The conservation of animals species included in this study were: the formosan gem-faced civets, leopard cats, tigers, clouded leopards, lion, formosan muntjacs, formosan sika deers, formosan sambars, formosan serows, water buffalo, formosan pangolins and formosan macaques. The control species used included domestic cats, domestic dogs, domestic sheeps, domestic cattles, domestic pigs and humans. Heteroplasmy was detected in the formosan macaque, domestic pig and domestic cats. The frequencies of heteroplasmy in these animals were about 0.25% (1 in 402bp). Sequences were aligned by Pileup program of GCG computer package, and the phylogenetic tree was constructed by the neighbor-joining method. The results of sequence comparison showed that the percentage range of sequence diversity in the same species was from 0.25 to 2.74%, and that between the different species was from 5.97 to 34.83%. The results of phylogenetic analysis showed that the genetic distance between the different species was from 6.33 to 40.59. Animals of the same species, both the endangered animal species and domestic animals, were clustered together in the neighbor-joining tree. Three unknown samples of animal remains were identified by this system. The partial sequence of cytochrome b gene adopted in this study proved to be usable for animal identification.

Animals↗

First order error propagation of the procrustes method for 3D attitude estimation.

The well-known Procrustes method determines the optimal rigid body motion that registers two point clouds by minimizing the square distances of the residuals. In this paper, we perform the first order error analysis of this method for the 3D case, fully specifying how directional noise in the point clouds affects the estimated parameters of the rigid body motion. These results are much more specific than the error bounds which have been established in numerical analysis. We provide an intuitive understanding of the outcome to facilitate direct use in applications.

Algorithms↗

Robustness of perception of heading from optic flow.

Heading discrimination in optic flow stimuli was investigated in 5 humans. Flow patterns consisted of a computer generated motion sequence which showed a mixture of randomly moving and coherently-moving points. The motion of the coherently-moving fiducial points was completely determined by the changing position of the observer's simulated vantage point. Ego-rotation as well as ego-translation was simulated. Noise and fiducial points were confined to the ground plane in most experiments. In one experiment the points formed a cloud with no visible horizon. The results indicate that heading perception is robust against degradation of the flow-field by the presence of noise or by the reduction of the lifetime of the fiducial points. The results suggest that points, which move independently from the reference frame as formed by the fiducial points, are to a large extent removed from the analysis of optic flow by the visual process which derives the heading. The motion of recognizable points at infinity (like the horizon) appears to be essential for robust heading perception in the presence of ego-rotations.

Adult↗

Development of sun compensation by honeybees: how partially experienced bees estimate the sun's course.

Honeybees and some other insects, in learning the sun's course, behave as if they can estimate the sun's position at times of day when they have never seen it, but there are competing ideas about the computational mechanisms underlying this ability. In an approach to this problem, we provided incubator-reared bees with opportunities to fly and see the sun only during the late afternoon. Then, on a cloudy day, we allowed bees to fly for the first time during the morning and early afternoon, and we observed how they oriented their waggle dances to indicate their direction of flight relative to the sun's position. The clouds denied the bees a direct view of celestial orientation cues and thus forced them to estimate the sun's position on the basis of their experience on previous evenings. During the test days, experience-restricted bees behaved during the entire morning as if they expected the sun to be in an approximately stationary position about 180 degrees from the average solar azimuth that they had experienced on previous evenings; then from about local noon onward they used the evening azimuth. This pattern suggests that honeybees are innately informed of the general pattern of solar movement, such that they can generate an internal representation that incorporates spatial and temporal features of the sun's course that they have never directly seen.

Journal Article↗

The CCPN data model for NMR spectroscopy: development of a software pipeline.

To address data management and data exchange problems in the nuclear magnetic resonance (NMR) community, the Collaborative Computing Project for the NMR community (CCPN) created a "Data Model" that describes all the different types of information needed in an NMR structural study, from molecular structure and NMR parameters to coordinates. This paper describes the development of a set of software applications that use the Data Model and its associated libraries, thus validating the approach. These applications are freely available and provide a pipeline for high-throughput analysis of NMR data. Three programs work directly with the Data Model: CcpNmr Analysis, an entirely new analysis and interactive display program, the CcpNmr FormatConverter, which allows transfer of data from programs commonly used in NMR to and from the Data Model, and the CLOUDS software for automated structure calculation and assignment (Carnegie Mellon University), which was rewritten to interact directly with the Data Model. The ARIA 2.0 software for structure calculation (Institut Pasteur) and the QUEEN program for validation of restraints (University of Nijmegen) were extended to provide conversion of their data to the Data Model. During these developments the Data Model has been thoroughly tested and used, demonstrating that applications can successfully exchange data via the Data Model. The software architecture developed by CCPN is now ready for new developments, such as integration with additional software applications and extensions of the Data Model into other areas of research.

Computer Graphics↗

Meteorological modeling of radioiodine transport and deposition within the continental United States.

A meteorological transport and deposition interpolation model has been employed to estimate radioiodine deposition remote from the Nevada Test Site between points of observed deposition. The movement of the radioactive cloud across the United States is obtained from wind trajectories at various quasi-constant levels up to the top of the initial radioactive cloud. This model deals primarily with depositions beneath the passing cloud that are associated with precipitation. The fraction of radioiodine scavenged was inferred from a relationship derived statistically from fallout at locations having wet deposition. Therefore, estimation of deposition at locations between fallout observations is possible wherever precipitation occurred under the cloud. These estimates use very detailed historical records of precipitation available for virtually every county in the United States. Because significant dry and wet depositions also occur in areas that are not beneath the cloud, interpolation methods, such as kriging, are used to estimate fallout between the radioactivity observation locations. Ground-level radioactivity measurements are required for these alternative methods. Such observations are validated before being used, often by the use of supplementary low-level trajectories.

Computer Simulation↗

The retina in forensic medicine: applications of ophthalmic endoscopy: the first 100 cases.

The retina reflects a variety of diseases in the living patient. However, the retina is not routinely examined in deceased persons, and therefore it is unknown if routine retinal examination would be a useful adjunct to the forensic autopsy. To examine this issue, the retinae of routine medical examiner cases were examined utilizing an ophthalmic endoscope. The results of the first 100 examinations are reported. Specific attention was given to changes that reflected the postmortem interval, the development of petechiae as related to cardiopulmonary resuscitation, and the association of retinal hemorrhages to subconjunctival hemorrhages. The procedure was helpful in cases of suspected shaken baby syndrome, exsanguination, and carbon monoxide poisoning and in cases with sudden increased intracranial pressure (Terson syndrome). It appears that lividity patterns exist in the retina, and this may be potentially useful in determining body position after death. Some natural disease processes, such as hypertension, were also identified. Finally, the utility of the ophthalmic endoscope as a means of circumventing the problem of corneal clouding is discussed, and ideas for further research using this technology are presented.

Adolescent↗

Benzimidazole derivatives. 3. 3D-QSAR/CoMFA model and computational simulation for the recognition of 5-HT(4) receptor antagonists.

A three-dimensional quantitative structure-affinity relationship study (3D-QSAR), using the comparative molecular field analysis (CoMFA) method, and subsequent computational simulation of ligand recognition have been successfully applied to explain the binding affinities for the 5-HT(4) receptor (5-HT(4)R) of a series of benzimidazole-4-carboxamides and carboxylates derivatives 1-24. The K(i) values of these compounds are in the range from 0.11 to 10 000 nM. The derived 3D-QSAR model shows high predictive ability (q(2) = 0.789 and r(2) = 0.997). Steric (contribution of 43.5%) and electrostatic (50.3%) fields and solvation energy (6.1%) of this novel class of 5-HT(4)R antagonists are relevant descriptors for structure-activity relationships. Computational simulation of the complexes between the benzimidazole-4-carboxamide UCM-21195 (5) and the carboxylate UCM-26995 (21) and a 3D model of the transmembrane domain of the 5-HT(4)R, constructed using the reported crystal structure of rhodopsin, have allowed us to define the molecular details of the ligand-receptor interaction that includes (i) the ionic interaction between the NH group of the protonated piperidine of the ligand and the carboxylate group of Asp(3.32), (ii) the hydrogen bond between the carbonyl oxygen of the ligand and the hydroxyl group of Ser(5.43), (iii) the hydrogen bond between the NH group of Asn(6.55) and the aromatic ring of carboxamides or the ether oxygen of carboxylates, (iv) the interaction of the electron-rich clouds of the aromatic ring of Phe(6.51) and the electron-poor hydrogens of the carbon atoms adjacent to the protonated piperidine nitrogen of the ligand, and (v) the pi-sigma stacking interaction between the benzimidazole system of the ligand and the benzene ring of Tyr(5.38). Moreover, the noticeable increase in potency at the 5-HT(4)R sites, by the introduction of a chloro or bromo atom at the 6-position of the aromatic ring, is attributed to the additional electrostatic and van der Waals interaction of the halogen atom in a small cavity located between transmembrane domains 5 and 6.

Animals↗

Severe acute pancreatitis caused by organophosphate poisoning.

Organophosphate intoxication may be caused pancreatitis, but the role of diagnostic imaging for pancreatitis in these patients has not been well defined. We recently encountered a patient with organophosphate poisoning showing hyperamylasemia who was proven to have severe acute pancreatitis by CT findings. The patient was a 69-year-old woman who presented to a local hospital with disturbance of consciousness. She was initially treated for cerebral infarction, but an extremely low level of ChE was noted on Day 3. The patient was then referred to our institution. Examination of the abdomen revealed weak intestinal peristalsis, blood chemistry showed an increased level of serum amylase, and the urinary organophosphate test was positive. Based on the findings obtained by abdominal CT scanning, severe acute pancreatitis was diagnosed. Clouding of her consciousness resolved on day 21, but a pancreatic pseudocyst was detected on day 41.

Acute Disease↗

Direct observation of completely processed calcium carbonate dust particles.

This study presents, for the first time, field evidence of complete, irreversible processing of solid calcium carbonate (calcite)-containing particles and quantitative formation of liquid calcium nitrate particles apparently as a result of heterogeneous reaction of calcium carbonate-containing mineral dust particles with gaseous nitric acid. Formation of nitrates from individual calcite and sea salt particles was followed as a function of time in aerosol samples collected at Shoresh, Israel. Morphology and compositional changes of individual particles were observed using conventional scanning electron microscopy with energy dispersive analysis of X-rays (SEM/EDX) and computer controlled SEM/EDX. Environmental scanning electron microscopy (ESEM) was utilized to determine and demonstrate the hygroscopic behavior of calcium nitrate particles found in some of the samples. Calcium nitrate particles are exceptionally hygroscopic and deliquesce even at very low relative humidity (RH) of 9-11% which is lower than typical atmospheric environments. Transformation of non-hygroscopic dry mineral dust particles into hygroscopic wet aerosol may have substantial impacts on light scattering properties, the ability to modify clouds and heterogeneous chemistry.

Journal Article↗

Is interstellar detection of higher members of the linear radicals CnCH and CnN feasible?

Rotational constants and dipole moments for linear-chain radicals CnCH and CnN are estimated using a combination of ab initio molecular orbital calculations and observed data on the starting members of the series. CnCH with n = 0-5 have been observed by radioastronomy in carbon-rich interstellar clouds; higher members of the series have 2 pi ground states with large dipole moments and are strong candidates for observation. CN and C3N have also been observed by radioastronomy; higher members of the series, with the possible exception of C5N, have 2 pi ground states with near-zero dipole moments making their interstellar detection hopeless under present observational conditions. C5N can be a strong candidate only if it has a 2 sigma ground state, and our best computations so far indicate that this is not the case.

Acetylene↗

Medical planning for toxic releases into the community: the example of chlorine gas.

Emergency planning for a major accidental release of chlorine gas from industrial installations into the community is outlined for emergency services and hospitals. Realistic planning has been made possible with the advent of computer models for gas dispersion which may be used to estimate the numbers of deaths and casualties, according to their severity. For most purposes sufficient accuracy may be obtained by using a small number of computer analyses for the most serious reasonably foreseeable events under typical day and night weather conditions, and allowing for the emergency response to be scaled up or down according to the size of an actual release. In highly populated areas triage should be preplanned to deal with a large number of victims; field stations will be needed for the treatment and observation of minor casualties. The management and treatment of casualties is summarised. The best protection against a gas cloud is afforded by buildings whose windows, doors, and ventilation systems have been closed. Hospitals in the vicinity of an installation should draw up plans to protect patients and staff. Coordination in a disaster will require toxicological and epidemiological expertise and hospital plans should allow for this.

Accidents, Occupational↗

Robot-enhanced fetoscopic surgery.

BACKGROUND: Fetoscopic surgery carries with it less maternal morbidity than open fetal surgery. Robotic surgery facilitates endoscopic surgery through tremor filtration, motion scaling, indexed movement, articulation, and improved ergonomics. The goal of the authors was to explore using a robotic surgery platform in a fetal animal model. METHODS: Using the Zeus Robotic Surgery System (Computer Motion, Santa Barbara, CA), fetoscopic surgery in pregnant sheep was performed using a variety of techniques: uterus exteriorized or totally percutaneous and with liquid or gas insufflation. Using the percutaneous technique and gas insufflation, the authors created and sutured fetal skin and fascial defects. The ewes were recovered and killed 2 weeks postoperatively, and autopsies were performed on them and their fetuses. RESULTS: In the exteriorized uterus model, instrument movement was unpredictable and fluid leaked. In the fluid environment, clouding of the visual field and difficulty in immobilizing the fetus were major difficulties. In the survival model, 4 of the 6 fetuses survived to autopsy at 2 weeks and showed good healing grossly and histologically. CONCLUSIONS: The Zeus Robotic Surgery System can be used for fetoscopic surgery in a sheep model. The percutaneous approach with a nitrous oxide environment is the most effective. Advantages of robotic surgery may be applicable in fetoscopic surgery, but further work in a primate model is required.

Animals↗