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Biomedical subjects

N A Clark

Publications and source records attributed to N A Clark.

At least 37 records · Page 2Linked to original sources

Time-resolved infrared spectroscopy of nematic-liquid-crystal electro-optic switching.

Time resolved infrared (IR) vibrational absorption spectroscopy is used to probe the dynamics of electric field-induced reorientation of the biphenyl molecular core and alkyl tail subfragments of the nematic liquid crystal 5CB (4-pentyl-4-cyanobiphenyl). The planar to homeotropic transition, induced by application of an electric field step to high pre-tilt planar aligned cells, is studied for switching times ranging from 200 micros down to 8 micros, the latter a factor of 1000 times faster than any previous nematic IR study. The reorientation rates of the core and tail are found to be the same to within experimental uncertainty, and scale inversely with applied field squared, as expected for the balance of field and viscous torques. Thus any molecular conformation change during switching must relax on a shorter time scale. A simple model shows that these data eliminate the possibility of there being substantial differences between the reorientational dynamics of the tails and cores on the time scales longer than on the order of 10 micros.

Journal Article↗

Influence of ions on the "V-shaped" electro-optic response of ferroelectric liquid crystals.

It has recently been shown that in surface-stabilized ferroelectric liquid crystal cells with high spontaneous polarization, the polarization charge self-interaction leads to a "V-shaped" optical response to an applied voltage. The presence of ionic free charges in the liquid crystal changes the internal electric field, and therefore also the spatial dependence of the polarization and optic axis orientation. We have numerically solved the nonlinear ion diffusion equation in the electric field due to external voltage, spontaneous polarization, and ions, and calculated the electro-optic response to a triangular applied voltage. When the period of the driving voltage is smaller than the zero-field diffusion time of the ions across the cell, and larger than the ion transit time in the applied field, an inverse hysteresis in the electro-optic response is obtained. At these time scales ions also cause characteristic changes in the shape of the electro-optic response.

Journal Article↗

Ring-pattern dynamics in smectic-C* and smectic-C*A freely suspended liquid crystal films.

Ring patterns of concentric 2pi solitons in molecular orientation form in freely suspended chiral smectic-C films in response to an in-plane rotating electric field. We present measurements of the driven dynamics of ring formation under conditions of synchronous winding and of the zero-field relaxation of ring patterns, and propose a simple model which enables their quantitative description in low polarization DOBAMBC. In smectic-C*A TFMHPOBC we observe an odd-even layer number effect, with odd layer number films exhibiting order of magnitude slower relaxation rates than even layer films. We show that this rate difference is due to a much larger spontaneous polarization in odd layer number films.

Journal Article↗

Increased rate of trazodone prescribing with bupropion and selective serotonin-reuptake inhibitors versus tricyclic antidepressants.

OBJECTIVE: To determine whether trazodone is prescribed significantly more often with selective serotonin-reuptake inhibitors (SSRIs) and bupropion than with tricyclic antidepressants (TCAs). METHODS: A retrospective analysis of Iowa City Department of Veteran's Affairs prescription records from March 1, 1995, to March 1, 1998, was performed. Antidepressants prescribed only by psychiatrists were included. Concomitant use was defined as trazodone prescribed on the same date or up to 42 days after the fill date of the primary antidepressant. STATISTICS: All comparisons used 2 x 2 chi 2 contingency table. Significance level was set at p < 0.05. RESULTS: Significantly more patients were prescribed trazodone concurrently with bupropion and SSRI antidepressants than with TCAs. Trazodone was prescribed significantly more often for patients receiving an SSRI (p = 0.0001, chi 2 = 14.59) or bupropion (p = 0.0295, chi 2 = 4.74) than for patients receiving a TCA. There was no significant difference in trazodone use between the patients taking SSRIs or bupropion. The percent of patients that received an SSRI, bupropion, or a TCA in combination with trazodone was 27%, 23%, and 13%, respectively. Overall, 23.7% of patients received trazodone concomitantly with a primary antidepressant. DISCUSSION: The effects of antidepressants on sleep and on sleep scores of depression rating scales are reviewed. The clinical implications of these findings are discussed. The literature addressing the effects of antidepressants on sleep and on sleep scores of depression rating scales is summarized. Although sleep studies suggest that SSRIs may not improve sleep as well as a TCA, clinical studies do not often support these findings. Several studies report that bupropion may not improve sleep parameters as well as doxepin or trazodone. The clinical implications of these findings are discussed. CONCLUSIONS: We have demonstrated that our clinicians prescribe trazodone at a significantly higher rate with an SSRI or bupropion than with a TCA. The exact reason for this difference is not known. If trazodone is used during the first six weeks of an initial antidepressant treatment trial, it should be discontinued to determine whether the patient's sleep disturbance has responded to the primary antidepressant. More comparison studies among the newer antidepressants and between classes of antidepressants concerning their effects on sleep in the depressed patient need to be performed.

Antidepressive Agents, Tricyclic↗

Titration of antiplatelet treatment in pregnant women at risk of preeclampsia.

We recruited 111 patients who were considered to be at significantly increased risk of preeclampsia on the basis of previous obstetric history or preexisting medical disorders. All patients were treated with low dose aspirin (75 mg/day) from the first occasion the patient attended the antenatal clinic, regardless of gestational age. If the maternal mean platelet volume (MPV) increased significantly (by > 0.8 fl) from the baseline, antiplatelet treatment was increased. Five pregnancies were lost during the second trimester and 106 of the treated patients had live infants. The incidence of neonatal death (3/106 infants) was much lower than in the previous pregnancies in these patients (32/134 infants). Patients who were treated from the first trimester of pregnancy (group A, 89 patients) did substantially better than those treated from the second trimester (group B, 17 patients) as assessed by the incidence of pre-eclampsia or intrauterine growth restriction (IUGR), gestational age and birthweight at delivery. These data suggest that longitudinal monitoring of the MPV may identify the women who could benefit from increased antiplatelet treatment, and that antiplatelet treatment may be more effective when initiated in the first trimester rather than later in pregnancy.

Abortion, Spontaneous↗

Applications of S-layers.

The wealth of information existing on the general principle of S-layers has revealed a broad application potential. The most relevant features exploited in applied S-layer research are: (i) pores passing through S-layers show identical size and morphology and are in the range of ultrafiltration membranes; (ii) functional groups on the surface and in the pores are aligned in well-defined positions and orientations and accessible for binding functional molecules in very precise fashion; (iii) isolated S-layer subunits from many organisms are capable of recrystallizing as closed monolayers onto solid supports at the air-water interface, on lipid monolayers or onto the surface of liposomes. Particularly their repetitive physicochemical properties down to the subnanometer scale make S-layers unique structures for functionalization of surfaces and interfaces down to the ultimate resolution limit. The following review focuses on selected applications in biotechnology, diagnostics, vaccine development, biomimetic membranes, supramolecular engineering and nanotechnology. Despite progress in the characterization of S-layers and the exploitation of S-layers for the applications described in this chapter, it is clear that the field lags behind others (e.g. enzyme engineering) in applying recent advances in protein engineering. Genetic modification and targeted chemical modification would allow several possibilities including the manipulation of pore permeation properties, the introduction of switches to open and close the pores, and the covalent attachment to surfaces or other macromolecules through defined sites on the S-layer protein. The application of protein engineering to S-layers will require the development of straightforward expression systems, the development of simple assays for assembly and function that are suitable for the rapid screening of numerous mutants and the acquisition of structural information at atomic resolution. Attention should be given to these areas in the coming years.

Bacteria↗

Automating Veterans Administration libraries: I. National planning and development.

The Veterans Administration Library Network (VALNET) needed an automated library system that could interface with the agency's national automation activities. The Library Special Interest Users Group was established to oversee the selection of appropriate automated systems. The Massachusetts General Hospital Utility Multi-Programming System (MUMPS) computer language and VA FILEMAN, a database management system, are being used to create new library software, which will be in the public domain.

Computer Communication Networks↗

X-ray diffraction and electron microscope study of phase separation in rod outer segment photoreceptor membrane multilayers.

Phase separation in artificially stacked multilayers of isolated bovine retinal rod outer segment (ROS) membranes has been examined via x-ray diffraction and electron microscopy. Specimens were prepared by isopotential spin drying followed with partial hydration by equilibration against moist gas streams. Upon dehydration, the multilamellar membrane phase assumes a binary phase composition consisting of concentrated protein-containing lamellae interspersed with microdomains of hexagonally packed tubes of lipid in a HII configuration. The HII lattice is geometrically coupled to the lamellar phase with one set of hexagonal crystal planes co-planar to the local membrane lamellae. The hexagonal microdomains bear a striking resemblance to the "paracrystalline inclusions" observed in fast-frozen, intact frog ROS (Corless and Costello. 1981. Exp. Eye Res. 32:217). The lamellar lattice is characterized by an unusually small degree of disorder. Sharp lamellar diffraction with a 120 A unit cell is observed (at near total dehydration) to a resolution of 6 A. A model consistent with the data is that a multilamellar array of ROS disks is stable as long as the external disk surfaces are kept sufficiently far apart. If the distance between the membranes is allowed to shrink below a certain critical value, the disk lipids spontaneously convert to a nonbilayer phase. This suggests that the structure of the ROS is stabilized by an internal framework that acts to keep the disks apart from one another and from the plasmalemma. Thus, the necessity of avoiding phase separations may provide a rationale for the peculiar morphology of the ROS.

Animals↗

Incorporation of photoreceptor membrane into a multilamellar film.

Multilamellar arrays of photoreceptor membrane up to 50 micrometer thick have been produced using a new method. Rhodopsin chromophore orientation in the films was studied using optical linear dichroism. The rhodopsin appears to be structurally intact and capable of photobleaching and regeneration. The production of biologically active liquid-crystal films offers a promising new approach to the study of biomembranes.

Animals↗

A spectroscopic study of rhodopsin alpha-helix orientation.

Polarized Fourier transform infrared spectroscopy and far ultraviolet circular dichroism of oriented multilamellar films of photoreceptor membranes indicate rhodopsin alpha-helices are predominantly oriented perpendicular to the bilayer plane.

Animals↗

Surface-induced lamellar orientation of multilayer membrane arrays. Theoretical analysis and a new method with application to purple membrane fragments.

The orientation of membrane fragments into a lamellar array by a flat surface is analyzed. This analysis includes processes such as centrifugation and drying and physical effects due to membrane fragment steric interactions, finite size, elasticity, and thermal fluctuations. Several model calculations of optimal orientational order in multilayer membrane arrays are presented. The predictions of a smectic A model agree quantitatively with the measured spatial dependence of the fluctuations in layer orientation in a multilamellar arrays. A new technique, based in part on this analysis, for the preparation of well-oriented multilamellar arrays of natural and artificial membranes, isopotential spin-dry centrifugation, is described. The method involves the use of specially designed inserts for the buckets of a standard vacuum ultracentrifuge. The membrane fragments to be oriented are sedimented from solution or suspension onto a substrate of a convenient material which forms a gravitational isopotential surface at high g. Sedimentation is accompanied by removal of the suspending medium at high g to produce oriented films with a selected degree of solvation. In addition, a method is described whereby small solute molecules can be maintained in constant concentration with the membrane fragments during this process. Initial application of the method to the orientation of purple membrane fragments is described. The degree of orientation obtained in this system is evaluated using freeze-fracture and scanning electron microscopy, optical birefringence, linear dichroism, and microscopy.

Bacteriorhodopsins↗

Anomalous amide I infrared absorption of purple membrane.

Infrared absorption of purple membrane reveals an amide I frequency that falls outside the range normally found for alpha helices. This may indicate along with x-ray diffraction the existence of bacteriorhodopsin alpha helices with unusual structure.

Amides↗

Polarized infrared spectroscopy of oriented purple membrane.

Polarized Fourier transform infrared spectroscopy has been used to study the structure of purple membrane from Halobacterium halobium. Membranes were oriented by drying a suspension of membrane fragments onto Irtran-4 slides. Dichroism measurements of the amide I, II and A peaks were used to find the average spatial orientation of the bacteriorhodopsin alpha-helices. By deriving a function that relates the observed dichroism to the orientational order parameters for the peptide groups, helical axis distribution, and mosaic spread of the membranes, the average orientation of the alpha-helices was found to lie in a range of less than 26 degrees away from the membrane normal, agreeing with electron microscopic measurements. The frequency of the amide I and A peaks is at least 10 cm-1 higher than values found for most alpha-helical polypeptides and proteins. This may indicate that bacteriorhodopsin contains distorted alpha-helical conformations.

Bacteriorhodopsins↗