Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “deep transfer model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1995

A role for quaternary structure in the substrate specificity of leucine dehydrogenase.

BACKGROUND: Glutamate, phenylalanine and leucine dehydrogenases catalyze the NAD(P)(+)-linked oxidative deamination of L-amino acids to the corresponding 2-oxoacids, and sequence homology between these enzymes clearly indicates the existence of an enzyme superfamily related by divergent evolution. We have undertaken structural studies on a number of members of this family in order to investigate the molecular basis of their differential amino acid specificity. RESULTS: We have solved the X-ray structure of the leucine dehydrogenase from Bacillus sphaericus to a resolution of 2.2 A. Each subunit of this octameric enzyme contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle. CONCLUSIONS: Comparison of the structure of leucine dehydrogenase with a hexameric glutamate dehydrogenase has shown that these two enzymes share a related fold and possess a similar catalytic chemistry. A mechanism for the basis of the differential amino acid specificity between these enzymes involves point mutations in the amino acid side-chain specificity pocket and subtle changes in the shape of this pocket caused by the differences in quaternary structure.

Amino Acid Oxidoreductases↗
PubMed1983

Similar binding of the carcinostatic drugs cis-[Pt(NH3)2Cl2] and [Ru(NH3)5Cl] Cl2 to tRNAphe and a comparison with the binding of the inactive trans-[Pt(NH3)2Cl2] complex - reluctance in binding to Watson-Crick base pairs within double helix.

A comparative study of the binding of square planar cis- and trans-[Pt(NH3)2Cl2] complexes and the octahedral [Ru(NH3)5(H2O)]3+ complex to tRNAphe from yeast was carried out by X-ray crystallography. Both of the carcinostatic compounds, cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ show similarities in their mode of binding to tRNA. These complexes bind specifically to the N(7) positions of guanines G15 and G18 in the dihydrouridine loop. [Ru(NH3)5(H2O)]3+ has an additional binding site at N(7) of residue G1 after extensive soaking times (58 days). A noncovalent binding site for ruthenium is also observed in the deep groove of the acceptor stem helix with shorter (25 days) soaking time. The major binding site for the inactive trans-[Pt(NH3)Cl2] complex is at the N(1) position of residue A73, with minor trans-Pt binding sites at the N(7) positions of residues Gm34, G18 and G43. The similarities in the binding modes of cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ are expected to be related to their carcinostatic properties.

Base Composition↗
PubMed1981

Membrane studies in Huntington's disease: steady state and time-dependent fluorescence spectroscopy of intact lymphocytes.

Recent evidence suggests that a membrane abnormality, expressed in peripheral tissues such as the lymphocyte, may be present in Huntington's disease (HD). Both steady state and time-dependent fluorescence spectroscopic methods were performed on lymphocytes from patients with HD and from age- and sex-matched controls. Lymphocyte membrane dynamics were studied, using fluorescence probes with known specificity for certain membrane areas. These probes included 4-phenylspiro(furan-2(3H)-1'-phthalan)-3,3'-dione (fluorescamine), which binds to surface membrane primary amines, 1-8-anilinonaphthalene sulfonate (1,8-ANS), which inserts at the aqueous-hydrocarbon interface, and 12(9) anthroyl stearate (12(9)AS), which inserts deep in the hydrocarbon core. Steady state fluorescence studies, using fluorescamine, 1-8 ANS, or 12(9)AS, revealed no significant difference between intact HD and control lymphocytes. Time-dependent energy-transfer polarization studies for fluorescamine (tryptophan leads to fluorescamine) did, however, reveal a slower time decay of (formula see text) for intact HD lymphocytes as compared with controls. This time-dependent difference may relate to alterations in translational (lateral) and angular mobilities of membrane donors (tryptophan) relative to acceptors (fluorescamine) in intact HD lymphocytes. Such observations support the concept of a membrane abnormality in HD.

Anilino Naphthalenesulfonates↗
PubMed1989

A new freeze-drying device for platinum replica studies of cell surface and cytoskeleton: an example using immunogold-labeled human erythrocytes.

We designed and built a freeze-drying device that ensures the protection of the specimens against contaminants during mounting on the cold stage of the freeze-fracture machine, transferring into the vacuum chamber and deep etching. The device consists of a copper cap that covers the specimen and a thermal connection that ensures thermal transfer between the microtome arm and the copper cap. This device was used to study the ultrastructural features of the erythrocyte membrane skeleton and the immunocytochemical localization of spectrin in an "in situ" approach, by freeze drying and platinum rotary shadowing. Human erythrocytes adhered to polylysine-coated coverslips and were broken by a stream of buffer that mimics the intracellular ionic environment ("inside buffer"). The samples were prefixed in periodate-lysine-paraformaldehyde fixative, labeled with antispectrin 5-nm gold particles, fixed in glutaraldehyde, mordanted in tannic acid, postfixed in OsO4, repeatedly washed in water, rinsed quickly in 30% ethanol, freeze-dried, and rotary-shadowed. Electron microscopic examination of the replicas revealed the skeletal network on the inner surface of the erythrocyte membrane. Immunocytochemical labeling proved that spectrin represents a fibrillar component of the network. Our data confirm the speculative model of the molecular organization of the erythrocyte skeleton, based on studies on in vitro association of proteic constituents. Both the technique and the device developed by us may lead to a deeper understanding of the spatial organization of the cytoskeletal network of more complex cell types.

Cytoskeleton↗
PubMed2005

Radiation safety assessment of a system of small reactors for distributed energy.

A passively safe small reactor for a distributed energy system, PSRD, is an integral type of light-water reactor with a thermal output of 100 or 300 MW aimed to be used for supplying district heat, electricity to small grids, and so on. Candidate locations for the PSRD as a distributed energy source are on-ground, deep underground, and in a seaside pit in the vicinity of the energy consumption area. Assessments of the radiation safety of a PSRD were carried out for three cases corresponding to normal operation, shutdown and a hypothetical postulated accident for several siting candidates. Results of the radiation safety assessment indicate that the PSRD design has sufficient shielding performance and capability and that the exposure to the general public is very low in the case of a hypothetical accident.

Algorithms↗
PubMed2007

Calcium indicators based on calmodulin-fluorescent protein fusions.

Calmodulin (CaM) is an ubiquitous protein involved in Ca2+-mediated signal transduction. On Ca2+ influx, CaM acquires a strong affinity to various cellular proteins with one or more CaM recognition sequences, resulting in the onset or termination of Ca2+-regulated cascades. Through nuclear magnetic resonance and crystallographic structural studies of these Ca2+-CaM complexes, we have gained a deep understanding of CaM target recognition mechanisms. One immediate application is the creation of protein-based Ca2+ sensors using CaM complexes and green fluorescent proteins, previously named "chameleon." The major advantage of chameleons is that they can be expressed in single cells and targeted to the specific organelles or tissues to measure localized Ca2+ changes. This chapter describes the methods involved in cloning chameleons, characterizing their biochemical and biophysical properties, and imaging them in single cells using a digital fluorescence microscope.

Calcium↗
PubMed2004

Does a tree-like phylogeny only exist at the tips in the prokaryotes?

The extent to which prokaryotic evolution has been influenced by horizontal gene transfer (HGT) and therefore might be more of a network than a tree is unclear. Here we use supertree methods to ask whether a definitive prokaryotic phylogenetic tree exists and whether it can be confidently inferred using orthologous genes. We analysed an 11-taxon dataset spanning the deepest divisions of prokaryotic relationships, a 10-taxon dataset spanning the relatively recent gamma-proteobacteria and a 61-taxon dataset spanning both, using species for which complete genomes are available. Congruence among gene trees spanning deep relationships is not better than random. By contrast, a strong, almost perfect phylogenetic signal exists in gamma-proteobacterial genes. Deep-level prokaryotic relationships are difficult to infer because of signal erosion, systematic bias, hidden paralogy and/or HGT. Our results do not preclude levels of HGT that would be inconsistent with the notion of a prokaryotic phylogeny. This approach will help decide the extent to which we can say that there is a prokaryotic phylogeny and where in the phylogeny a cohesive genomic signal exists.

Bacteria↗
PubMed1994

Psychotherapy: the search for chaos and the discovery of determinism.

The search for a science of psychoanalysis is introduced by defining three modes of psychoanalytic science: domain, statistical-stochastic, and formal. The paper outlines the domain science propositions of the communicative approach to psychoanalytic psychotherapy and indicates how this version of psychoanalytic theory led to the development of an extensive series of statistical-stochastic and formal science studies of the communications between patients and therapists. The formal science efforts which began as a mathematical search for chaotic attractors revealed instead a deep determinism within the psychotherapeutic dialogue. Three specific laws of the mind and human communication have been identified. The research is centred on how we communicate (the communicative vehicle) rather than what we express (the contents). After describing a wide range of unexpected and unprecedented results, the paper concludes with a discussion of some of the clinical implications of these findings and of the new formal science of psychoanalysis created by these investigations.

Communication↗
PubMed2002

Can intubation harm the brain in critical care situations? A new simple technique may provide a method for controlling brain temperature.

Many animal species are able to keep the brain temperature some degrees centigrade lower than the deep body temperature when exposed to environmental heat stress. The lower temperature is based on cooling of the nasal venous blood through the respiratory airflow and local counter-current transfer of heat between venous and arterial blood in the cavernous sinus-carotid artery complex. Anaesthetized, intubated animals do not have any air flow through the nasal cavities. However, when the nasal cavities were flushed with oxygen, the deep brain temperature dropped within minutes and returned to previous values when the oxygen flushing was stopped. Cooling was found in animals with a rete mirabile (pigs), and in animals without a rete (rats). If a similar cooling mechanism is present in man (no rete) under intensive care, a simple flushing of the nasal cavities with gas will protect the brain against hyperthermal damage.

Animals↗
PubMed2026

Vortex-assisted liquid-liquid microextraction based on natural deep eutectic solvents for the determination of pyrethroid pesticides in urine.

A novel, facile, and environmentally friendly analytical method was developed based on vortex-assisted liquid-liquid microextraction and high-performance liquid chromatography with diode-array detection for detecting pyrethroid pesticides (PPs) in urine. Natural deep eutectic solvents (NADESs) were prepared using plant essential oil-derived monoterpenoids (thymol, carvacrol, and menthol) combined with aromatic primary alcohols (benzyl alcohol, phenethyl alcohol, and phenylpropyl alcohol) as hydrogen bond donors and acceptors. These solvents served as environmentally benign extraction media, thereby avoiding the use of conventional volatile, toxic organic solvents. NADESs are naturally derived, easy to prepare, biodegradable, and environmentally friendly solvents. Hydrophobic and π-π interactions between the NADESs and PPs may contribute to enhancing the affinity of PPs toward the NADESs phase. Vortex technology, accelerating mass transfer between the sample and extractant phases, enables fast extraction of PPs. Under optimized conditions, the method achieved a low detection limit (0.002 mg L-1), satisfactory precision with relative standard deviations (0.3%-2.4%), and acceptable recovery (80.7%-86.2%). The method demonstrated excellent performance in urine analysis and was feasible as a facile and green strategy for monitoring the content of PPs in biological matrices and assessing exposure risk.

Liquid Phase Microextraction↗
PubMed1990

Interaction of RNase P from Escherichia coli with pseudoknotted structures in viral RNAs.

In a previous study it was shown that RNase P from E. coli cleaves the tRNA-like structure of turnip yellow mosaic virus (TYMV) RNA in vitro (Guerrier-Takada et al. (1988) Cell, 53, 267-272). Cleavage takes place at the 3' side of the loop that crosses the deep groove of the pseudoknot structure present in the aminoacyl acceptor domain. In the present study fragments of TYMV RNA with mutations in the pseudoknot, generated by transcription in vitro, were tested for susceptibility to cleavage by RNase P. Changes in the specificity with respect to the site of cleavage and decreases in the rate of cleavage were observed with most of these substrates. The behaviour of various mutants in the reaction catalyzed by RNase P is in agreement with the present model of the TYMV RNA pseudoknot (Dumas et al. (1987), J. Biomol. Struct. Dyn. 263, 652-657). Base substitutions in the loop that crosses the shallow groove of the pseudoknot structure resulted, however, in an unexpected decrease in the rate of cleavage, probably due to conformational changes in the substrates. Studies on other tRNA-like structures revealed an important role in the reaction with RNase P for both the nucleotide at the 3' side of the loop that spans the deep groove and the nucleotide at position 4, which correspond to positions--1 and 73, respectively, in tRNA precursors.

Base Sequence↗
PubMed2006

Ionisation density dependence of the optically and thermally stimulated luminescence from Al2O3:C.

This paper presents an overview of recent results on ionisation density dependence of the thermally stimulated luminescence (TL) and optically stimulated luminescence (OSL) signals from Al2O3:C, with emphasis on the sensitivity, efficiency, shape of the TL/OSL curves and the emission spectrum. High-ionisation densities are created uniformly by accumulated high doses of low-linear energy transfer radiation (gamma, beta, X rays) or non-uniformly in heavy charged particle tracks, even at low fluences, as in the case of space radiation fields. Significant deep trap filling, which occurs at these high-ionisation densities, ultimately results in changes in the concentration of recombination centres (F+-centres) and, consequently, in sensitivity changes and other effects. An OSL emission band at 335 nm has been observed in addition to the main F-centre luminescence band, and the relative intensities of these bands have been observed to be dependent on the ionisation density. The implications of these results and open issues are discussed.

Aluminum Oxide↗
PubMedDate not supplied

MR imaging-related heating of deep brain stimulation electrodes: in vitro study.

BACKGROUND AND PURPOSE: Recent work has shown a potential for excessive heating of deep brain stimulation electrodes during MR imaging. This in vitro study investigates the relationship between electrode heating and the specific absorption rate (SAR) of several MR images. METHODS: In vitro testing was performed by using a 1.5-T MR imaging system and a head transmit-receive coil, with bilateral deep brain stimulation systems positioned in a gel saline-filled phantom, and temperature monitoring with a fluoroptic thermometry system. Standardized fast spin-echo sequences were performed over a range of high, medium, and low SAR values. Several additional, clinically important MR imaging techniques, including 3D magnetization prepared rapid acquisition gradient-echo imaging, echo-planar imaging, quantitative magnetization transfer imaging, and magnetization transfer-suppressed MR angiography, were also tested by using typical parameters. RESULTS: A significant, highly linear relationship between SAR and electrode heating was found, with the temperature elevation being approximately 0.9 times the local SAR value. Minor temperature elevations, <1 degrees C, were found with the fast spin-echo, magnetization prepared rapid acquisition gradient-echo, and echo-planar clinical imaging sequences. The high dB/dt echo-planar imaging sequence had no significant heating independent of SAR considerations. Sequences with magnetization transfer pulses produced temperature elevations in the 1.0 to 2.0 degrees C range, which was less than theoretically predicted for the relatively high SAR values. CONCLUSION: A potential exists for excessive MR imaging-related heating in patients with deep brain stimulation electrodes; however, the temperature increases are linearly related to SAR values. Clinical imaging sequences that are associated with tolerable temperature elevations in the <or=2.0 degrees C range at the electrode tips can be performed safely within an SAR range <2.4 W/kg local (0.9 W/kg whole body averaged).

Body Temperature↗
PubMed2004

Arabidopsis to rice. Applying knowledge from a weed to enhance our understanding of a crop species.

Although Arabidopsis is well established as the premiere model species in plant biology, rice (Oryza sativa) is moving up fast as the second-best model organism. In addition to the availability of large sets of genetic, molecular, and genomic resources, two features make rice attractive as a model species: it represents the taxonomically distinct monocots and is a crop species. Plant structural genomics was pioneered on a genome-scale in Arabidopsis and the lessons learned from these efforts were not lost on rice. Indeed, the sequence and annotation of the rice genome has been greatly accelerated by method improvements made in Arabidopsis. For example, the value of full-length cDNA clones and deep expressed sequence tag resources, obtained in Arabidopsis primarily after release of the complete genome, has been recognized by the rice genomics community. For rice >250,000 expressed sequence tags and 28,000 full-length cDNA sequences are available prior to the completion of the genome sequence. With respect to tools for Arabidopsis functional genomics, deep sequence-tagged lines, inexpensive spotted oligonucleotide arrays, and a near-complete whole genome Affymetrix array are publicly available. The development of similar functional genomics resources for rice is in progress that for the most part has been more streamlined based on lessons learned from Arabidopsis. Genomic resource development has been essential to set the stage for hypothesis-driven research, and Arabidopsis continues to provide paradigms for testing in rice to assess function across taxonomic divisions and in a crop species.

Arabidopsis↗
PubMed1996

A three-compartment open pharmacokinetic model can explain variable toxicities of cobra venoms and their alpha toxins.

The pharmacokinetic profiles of labelled Naja melanoleuca, Naja nivea, Naja nigricollis and Naja haje venoms and their alpha neurotoxins were determined following rapid i.v. injection into rabbits. The data obtained fitted a triexponential equation characteristic of a three-compartment open pharmacokinetic model comprising a central compartment 'blood', a rapidly equilibrating 'shallow' tissue compartment and a slowly equilibrating 'deep' tissue compartment. The distribution half-lives for the shallow compartment ranged from 3.2 to 5 min, reflecting the rapid uptake of venoms and toxins compared with 22-47 min for the deep tissue compartment denoting much slower uptake. The overall elimination half-lives, t1/2 beta, ranged from 15 to 29 hr, indicating a slow body elimination. Peak tissue concentration was reached within 15-20 min in the shallow tissue compartment. The corresponding values for the deep tissue compartment were 120 min for N. melanoleuca and N. nigricollis venoms and their toxins and 240 min for N. nivea and N. haje venoms and their toxins. Steady-state distribution between the shallow tissue compartment and the blood gave values of 0.50 and 0.92 (N. melanoleuca), 1.64 and 1.05 (N. nivea), 0.78 and 0.92 (N. nigricollis) and 1.70 and 1.03 (N. haje) for the venoms and their toxins, respectively. The corresponding values for the deep tissue compartment gave ratios of 3.31 and 3.44 (N. melanoleuca), 2.99 and 1.68 (N. nivea), 3.74 and 3.79 (N. nigricollis) and 1.39 and 2.46 (N. haje) for the venoms and their toxins, respectively. Ratios lower than unity indicate lower venom and toxin concentrations in the tissues than in the blood, while larger ratios denote higher tissue concentrations. The values thus reflect a higher affinity of the venoms and their toxins for the central than the shallow tissue compartment and for the deep tissue than the central compartment. The sites of action of the venoms seem to be located in the deep tissue compartment since most of the pharmacological, biochemical and electrocardiographic effects of the venoms started 30-60 min after i.v. injection. The mean residence time in the body, MRTb, ranged from 20.8 to 51.8 hr, which correlated well with the long duration of the pharmacological and biochemical effects induced by the venoms. The tissue distribution of the venoms and toxins was similar, with the highest uptake being in the kidneys, followed by the stomach, lungs, liver, spleen, intestine, heart and diaphragm. Very high radioactivity was found in the stomach contents, which reached values higher than the kidneys. Some of the biochemical markers were significantly changed by one or more venoms but the grouped parameters did not reflect significant changes in cardiac, renal, hepatic or electrolyte profiles as a function of time. It is concluded that antivenom, even if injected several hours after a cobra bite, is still capable of neutralizing the slowly eliminating venom. To speed up neutralization of the venom effects, doses of antivenom higher than the calculated in vitro neutralizing dose ought to be injected to compensate for the slow rate of transfer of antivenom to the tissues.

Animals↗
PubMed1989

Optimization of the absorbed power distribution for an annular phased array hyperthermia system.

One of the systems under investigation for producing hyperthermia noninvasively for treating deep-seated tumors is the annular phased array. This device consists of two rings of eight electromagnetic apertures that are placed concentrically about the long axis of the patient and radiate energy toward the center. Previous theoretical and clinical studies have concentrated primarily on systems where the amplitude and phase of the signal applied to each aperture were the same, and these studies have shown that the system is capable of depositing power deep within the patient. Nevertheless, in many situations the system was not capable of producing desirable temperature distributions in the tumor and normal tissue. In this paper we report on a 2-dimensional theoretical investigation where an optimization routine was used to select the amplitude and phases of each of eight apertures. The optimization procedure and resulting calculations were based on CT scans of patients with tumors. The electrical and thermal properties of the different organs and tissues were taken into account. The optimization routine tried to achieve uniform absorbed power in the tumor region with zero absorbed power outside. Using the optimized amplitudes and phases, the SAR (specific absorption rate, W/kg) was calculated for the array. The results show that in general the optimization procedure was successful in that the power deposited within the tumor volume was increased with less power deposited into normal tissue when compared to the equal amplitude and phase case. This SAR data was then used as the input to a program based on the bioheat transfer equation, which calculated the temperature distribution in the patient model for an assumed set of blood perfusion rates. Depending on the location, size of the tumor, and blood perfusion rates, the improvement in the percentage of the tumor brought to therapeutic temperature varied from 0% to as much as 80%.

Humans↗
PubMed1998

Assessment and requirements of nuclear reaction databases for GCR transport in the atmosphere and structures.

The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) are of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.

Aerospace Medicine↗
PubMed1996

Photophysics of Supercomplexes. Adduct between Ru(bpy)(CN)(4)(2-) and the [32]ane-N(8)H(8)(8+) Polyaza Macrocycle.

The formation of a supercomplex between the Ru(bpy)(CN)(4)(2-) (bpy = 2,2'-bipyridine) complex and the [32]ane-N(8)H(8)(8+) macrocycle (1) has been studied in water and in acetonitrile. In acetonitrile, supercomplex formation is accompanied by (i) large hypsochromic shifts in the absorption spectrum (color changes from deep violet to yellow) and in the emission spectrum, (ii) large anodic shifts in standard oxidation (0.73 V) and reduction (0.37 V) potentials, (iii) typical shifts of (1)H-NMR signals for the macrocycle N-bound protons and the complex bipyridine protons, and (iv) a large increase in the MLCT excited-state lifetime of the complex. In water, the spectral shifts and the changes in standard potential are much less pronounced, but supercomplex formation is evidenced by (13)C-NMR (and (1)H-NMR) and by emission lifetime changes. In both solvents, supercomplex formation is complete in 1:1, 1.0 x 10(-4) M solutions, indicating very large stability constant values. A structure of the supercomplex with the macrocycle bound in a "boat" conformation to the four cyanide ligands of the complex, plausible in terms of molecular models, is consistent with all the experimental data. In water, the supercomplex further associates with added negative species containing carboxylate functions, as shown by partial reversal of the lifetime changes. When the added species is also a potential electron transfer quencher (such as, e.g., Rh(dcb)(3)(3-), dcb = 4,4'-dicarboxy-2,2'-bipyridine), however, association is not accompanied by quenching. This behavior is attributed to the structure of the supercomplex-quencher adduct, in which the macrocycle acts as an insulating spacer between the excited complex and the quencher.

Journal Article↗