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At least 469 records · Page 26Linked to original sources

PubMed1997

A molecular switch for biochemical logic gates: conformational studies.

This report presents the computer-assisted design of a molecular switching element, in which a molecular switch regulates the enzymatic activity of Ribonuclease A (RNase A). The molecular switch, an appropriately modified amino acid residue, is constructed with an electron donor group and an electron acceptor group, connected to one another with a conjugated double bond bridge. The switching mechanism is based on the azonium-hydrazo tautomerization, by which a charge separation induced in the excited state causes a rearrangement of the molecular electronic structure, resulting in the exchange of locations of single and double bonds. This rearrangement of bonds leads to different three-dimensional conformations of the switch. Using the electrostatically driven Monte Carlo (EDMC) method and the empirical conformational energy program for peptides (ECEPP/3) potential energy function, we carried out an exhaustive search of the conformational space of the switching element. The results of these calculations reveal two sets of conformations: in one set the access to the active site of the enzyme is preferentially blocked, while in the other set the active site is preferentially accessible. Integration of the designed element into biochemical logic gates operating under the rules of threshold value, and experimental implementation of this system, are considered.

Protein Conformation↗

PubMed2006

High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington's disease.

Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration technique. This is driven by the in-plane point spread function for images acquired in the Fourier domain with data obtained over a bounded region of k-space, namely the sinc interpolation function, where sinc z = (sin z)/z, with z being any complex number (including zero). Computational subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired scan data allows for the determination of structural cerebral changes with great precision, since voxel signals from unchanged structures are almost completely cancelled. Thus changes readily show up against a background of noise. Furthermore, lateral ventricular changes can now be accurately quantified using a semi-automated method involving contour production, threshold computation, binary image creation and ventricular extraction. These techniques have been applied to the investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia, treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and Huntington's disease.

Atrophy↗

PubMed2003

Efficiencies of transgene expression in nociceptive neurons through different routes of delivery of adeno-associated viral vectors.

Transferring therapeutic genes into the nociceptive system, including dorsal root ganglia (DRGs) and the spinal cord, is potentially a powerful approach for the treatment of chronic pain in humans. Adeno-associated viral vectors (AAVs) are particularly useful in delivering foreign genes to targeted tissues because they seldom induce immune responses or produce cytotoxicity. To determine the efficiency of transgene expression and the best route(s) of delivery, a recombinant AAV type 2 vector containing the enhanced green fluorescent protein (EGFP) gene driven by the neuron-specific enolase (NSE) promoter (rAAV-EGFP) was constructed. We injected the vector into subcutaneous tissue, sciatic nerve, DRGs, and subarachnoid space, and examined EGFP expression in the DRG, spinal cord, and nerve fibers. Both sciatic nerve and DRG injection led to strong EGFP expression in a large number of DRG neurons. The expression persisted for more than 6-8 months. We then delivered the mu-opioid receptor (muOR) gene into DRGs through direct DRG or sciatic nerve injection of rAAV-muOR and found a significant increase in morphine efficacy. These results suggest that delivering therapeutic genes to DRGs by the rAAV-NSE vector is a valid strategy for treatment of chronic pain.

Analgesics, Opioid↗

PubMed2003

Observation of nonlinear frequency-sweeping suppression with rf diffusion.

Nonlinear frequency sweeping of unstable waves in a laboratory plasma is suppressed upon application of rf fields. Frequency sweeping is driven by a population of energetic electrons trapped in a magnetic dipole field that excite drift-resonant potential fluctuations and create coherent structures in phase space. Self-consistent numerical simulation reproduces the suppression and suggests an explanation due to rf scattering of energetic electrons that destroys the phase-space structures.

Journal Article↗

PubMed1973

Solute distribution in sugar beet leaves in relation to Phloem loading and translocation.

The distribution of solutes in the various cells of sugar beet (Beta vulgaris L.) source leaves, petioles, and sink leaves was studied in tissue prepared by freeze-substitution. The differences in degree of cryoprotection indicated that sieve elements and companion cells of the source leaf, petiole, and sink leaf contain a high concentration of solute. The osmotic pressure of various types of cells was measured by observing incipient plasmolysis in freeze-substituted tissues equilibrated with a series of mannitol solutions prior to rapid freezing. Analysis of source leaf tissue revealed osmotic pressure values of 13 bars for the mesophyll and 30 bars for the sieve elements and companion cells. The osmotic pressure of the mesophyll of sink leaves was somewhat higher.The sharp concentration increase at the membrane of the sieve element-companion cell complex of the source leaf indicates active phloem loading from the free space at this site. Active loading of the phloem is presumably needed to move the sugar from the chloroplasts of the mesophyll to the sieve tubes against the concentration gradient. The osmotic pressure of the mature sieve element-companion cell complex appears to be approximately the same in source leaf, path, and sink leaf tissue. There is a distinct difference in concentration between the mature sieve element-companion cell complex in the sink and the surrounding mesophyll. The solute distribution suggests that sugar is actively accumulated from the free space by the developing sink leaf tissue.The osmotic values observed in the various cells are consistent with the operation of a mass flow mechanism of translocation driven by active phloem loading and by active accumulation of sugar by sink tissues.

Journal Article↗

PubMed1995

Functional effects of a natural polymorphism in the transcriptional regulatory sequence of HLA-DQB1.

DNA sequence polymorphism in the genes encoding HLA class II proteins accounts for allelic diversity in antigen recognition and presentation and, thus, in the role of these cell surface glycoproteins as determinants of the scope of the T-cell repertoire. In addition, sequence polymorphism in the promoter-proximal transcriptional regulatory regions of these genes has been described, particularly for the HLA-DQB1 locus, where these differences may contribute to variation in locus- and allele-specific expression. In this study, we measured the effect of such regulatory sequence polymorphism on the expression of endogenous alleles of DQB1 in heterozygous cells. Quantitative reverse transcriptase-mediated PCR analysis showed that expression of the DQB1*0301 allele responded more rapidly to gamma interferon induction than that of DQB1*0302. We have analyzed functional effects of a prominent allelic polymorphism that consists of a TG dinucleotide present between the W and X1 consensus elements in the DQB1*0302 allele but missing in the DQB1*0301 allele. The dominant effect of this polymorphism was to introduce a variation in the spacing between the W and X1 elements of these two alleles. A secondary compensatory effect was specific for the TG dinucleotide itself, which was essential for the binding of a nuclear protein complex to the *0302 regulatory region immediately 5' of the X1 element. Derivatives of the DQB1 5' regulatory region were used to drive expression of the chloramphenicol acetyltransferase gene in transient transfections of human B-lymphoblastoid and gamma interferon-treated melanoma cell lines, demonstrating that the additional spacing between the W and X1 elements caused by the presence of the TG dinucleotide in the *0302 allele resulted in reduced expression compared with that driven by the *0301 fragment; this difference overshadowed an up-regulating effect on expression which corresponded to the binding of the TG-dependent nuclear protein complex. The presence of this polymorphism in multiple HLA-DQB1 alleles and in several species suggests selection for two alternative transcriptional regulatory mechanisms influencing expression of alleles of the same HLA locus.

Alleles↗

PubMed1990

Development of a new microsurgical robot for stereotactic neurosurgery.

The robot technology was introduced into a new stereotactic neurosurgery system for applications to biopsy, blind surgery, and functional neurosurgery. The authors have developed a newly designed prototype microsurgical robot, designed to allow a biopsy needle to reach the target such as a cerebral tumor within a brain automatically on the basis of the X, Y, and Z coordinates obtained by CT scanner. This robot is so small that it can be driven in a CT scanner gantry. It consists mainly of the link mechanism and the insertion mechanism. We constructed the link mechanism and investigated its working space.

Biopsy, Needle↗

PubMed2006

The great intimidators.

After Disney's Michael Eisner, Miramax's Harvey Weinstein, and Hewlett-Packard's Carly Fiorina fell from their heights of power, the business media quickly proclaimed thatthe reign of abrasive, intimidating leaders was over. However, it's premature to proclaim their extinction. Many great intimidators have done fine for a long time and continue to thrive. Their modus operandi runs counter to a lot of preconceptions about what it takes to be a good leader. They're rough, loud, and in your face. Their tactics include invading others' personal space, staging tantrums, keeping people guessing, and possessing an indisputable command of facts. But make no mistake--great intimidators are not your typical bullies. They're driven by vision, not by sheer ego or malice. Beneath their tough exteriors and sharp edges are some genuine, deep insights into human motivation and organizational behavior. Indeed, these leaders possess political intelligence, which can make the difference between paralysis and successful--if sometimes wrenching--organizational change. Like socially intelligent leaders, politically intelligent leaders are adept at sizing up others, but they notice different things. Those with social intelligence assess people's strengths and figure out how to leverage them; those with political intelligence exploit people's weaknesses and insecurities. Despite all the obvious drawbacks of working under them, great intimidators often attract the best and brightest. And their appeal goes beyond their ability to inspire high performance. Many accomplished professionals who gravitate toward these leaders want to cultivate a little "inner intimidator" of their own. In the author's research, quite a few individuals reported having positive relationships with intimidating leaders. In fact, some described these relationships as profoundly educational and even transformational. So before we throw out all the great intimidators, the author argues, we should stop to consider what we would lose.

Commerce↗

PubMed1998

Ontogenetic scaling of foraging rates and the dynamics of a size-structured consumer-resource model.

The ontogenetic scaling of foraging capacity strongly influences the competitive ability of differently sized individuals within a species. We develop a physiologically structured model to investigate the effect of different ontogenetic size scalings of the attack rate on the population dynamics of a consumer-resource system. The resource is assumed to reproduce continuously whereas the consumer only reproduces at discrete time instants. Depending on the ontogenetic size scaling, the model exhibited recruit-driven cycles, stable fixed point dynamics, non-recruit juvenile-driven cycles, quasiperiodic orbits, or chaotic dynamics. The kind of dynamics observed was related to the maintenance resource levels required of differently sized individuals. Stable fixed point dynamics was, besides at the persistence boundary, only observed when the minimum resource levels were similar for newborns and mature individuals. The tendency for large population fluctuations over a wide range of the parameter space was due to the consumer's pulsed reproduction. Background mortality and length of season were major determinants of cycle length. Model dynamics strongly resembled empirically observed dynamics from fish and Daphnia populations with respect to both patterns and mechanisms. The non-recruit juvenile-driven dynamics is suggested to occur in populations with size-dependent interference or preemptive competition like cicada populations.

Animals↗

PubMed2006

Structural phase transition and hydrogen ordering of TlH2PO4 at low temperature.

The crystal structure of TlH(2)PO(4) (TDP) has been studied at low temperature. The lattice parameters were derived from high-resolution X-ray powder diffraction in the temperature range between 8 and 300 K. A detailed crystal structure analysis of the antiferroelectric low-temperature phase TDP-III has been performed based on neutron diffraction data measured at 210 K on a twinned crystal consisting of two domain states. The structure model in the triclinic space group P\bar 1 is characterized by a complete ordering of all the H atoms in the asymmetric O-H...O hydrogen bonds. The phase transition from the ferroelastic TDP-II to the antiferroelectric TDP-III phase at 229.5 +/- 0.5 K is only slightly of first order and shows no detectable hysteresis effects. Its mechanism is driven by the hydrogen ordering between the partially ordered TDP-II state and the completely ordered TDP-III state. The polymorphism of TDP and the fully deuterated TlD(2)PO(4) (DTDP) is presented in the form of group-subgroup relations between the different space groups.

Journal Article↗

PubMed2004

Philosophical instruments and toys: optical devices extending the art of seeing.

Philosophical instruments were designed to examine phenomena experimentally, rather than by naturalistic observation alone. In the nineteenth century, some instruments were called philosophical toys because they provided popular amusement as well as experimental assistance. They were applied widely in natural philosophy, but attention here is directed particularly to manipulations of perceived space and time and their influence on art. One of the earliest instruments, which had a profound impact on art as well as science, was the camera obscura. It assisted image formation in art before it was applied as an analogy to the eye at the beginning of the seventeenth century. Later philosophical toys were used to address visual perception of motion and depth. Development was initially driven by the need for stimulus control so that the methods of physics could be applied to the study of perceptual phenomena. The principal instruments were invented in the first half of the nineteenth century, and they consisted of simple contrivances that manipulated time and space in ways that had not previously been appreciated. They included thaumatropes, phenakistoscopes, stroboscopes, anorthoscopes, stereoscopes, tachistoscopes, and chronoscopes. Several of these philosophical toys proved to be phenomenally popular, particularly when combined with photography.

History, 16th Century↗

PubMed1994

Tomorrow's library.

The buildings in which we house libraries are like other special purpose structures; the needs they fill are significantly influenced by technology. A prime function of the library building is to house collections (of people, material, and systems) as well as collections of collections (networks). Electronic formats for library material offer new approaches to information service delivery. An example, the information access station, typifies how traditional functions can be reconfigured with respect to space. Flexible design can help ensure that tomorrow's libraries meet the users' needs, but we need to question all our assumptions about building design including those driven by our understanding of the browsing process.

Facility Design and Construction↗

PubMed2006

Animal models of obesity-associated chronic kidney disease.

Dramatic advances in basic science have been made in the past 50 years on the basis of animal models of obesity and type II diabetes. Positional-cloning strategies in rodents with spontaneous obesity have enabled landmark scientific breakthroughs and defined the molecular scaffolding for the regulation of energy homeostasis. Recently, studies in the general population suggest that obesity is an independent risk factor for chronic kidney disease. To date, most of the animal studies that investigated chronic kidney disease associated with obesity and type II diabetes have largely been descriptive. We aim to provide an overview of animal models used to investigate the mechanisms of obesity-associated chronic kidney disease. Our overview is not meant to be an exhaustive list of all animal models in the literature on this subject, but rather to illustrate the experimental approaches. Because of space limitations, we have chosen to concentrate on rodent models. These animal models will provide excellent tools for in vivo testing of molecular mechanisms. Further hypothesis-driven research into the mechanism of chronic kidney disease and their progression by use of these models will provide important insights necessary to develop therapeutic strategies for this significant complication of the worldwide epidemic of obesity and type II diabetes.

Animals↗

PubMed2004

Field of genes: the politics of science and identity in the Estonian Genome Project.

This case study of the Estonian Genome Project (EGP) analyses the Estonian policy decision to construct a national human gene bank. Drawing upon qualitative data from newspaper articles and public policy documents, it focuses on how proponents use discourse to link the EGP to the broader political goal of securing Estonia's position within the Western/European scientific and cultural space. This dominant narrative is then situated within the analytical notion of the "brand state", which raises potentially negative political consequences for this type of market-driven genomic research. Considered against the increasing number of countries engaging in gene bank and/or gene database projects, this analysis of Estonia elucidates issues that cross national boundaries, while also illuminating factors specific to this small, post-Soviet state as it enters the global biocybernetic economy.

Databases, Nucleic Acid↗

PubMed2004

Sonoelastographic imaging of interference patterns for estimation of the shear velocity of homogeneous biomaterials.

The shear wave velocity is one of a few important parameters that characterize the mechanical properties of bio-materials. In this paper, two noninvasive methods are proposed to measure the shear velocity by inspecting the shear wave interference patterns. In one method, two shear wave sources are placed on the opposite two sides of a sample, driven by the identical sinusoidal signals. The shear waves from the two sources interact to create interference patterns, which are visualized by the vibration sonoelastography technique. The spacing between the pattern bands equals half of the shear wavelength. The shear velocity can be obtained by taking the product of the wavelength and the frequency. An alternative method is to drive the two vibration sources at slightly different frequencies. In this case, the interference patterns no longer remain stationary. It is proved that the apparent velocity of the moving patterns is proportional to the shear velocity in the medium. Since the apparent velocity of the patterns can be measured by analysing the video sequence, the shear velocity can be obtained thereafter. These approaches are validated by a conventional shear wave time-of-flight approach, and they are accurate within 4% on various homogeneous tissue-mimicking phantoms.

Connective Tissue↗

PubMed2002

Interface view of directed sandpile dynamics.

We present a directed unloading sand-box-type avalanche model, driven by slowly lowering the retaining wall at the bottom of the slope. The avalanche propagation in the two-dimensional surface is related to the space-time configurations in one-dimensional Kardar-Parisi-Zhang (KPZ) interface growth. We relate the scaling exponents of the avalanche cluster distribution to those for the growing surface. The numerical results are close but deviate significantly from the exact KPZ values. This might reflect stronger than usual corrections to scaling or be more fundamental, due to correlations between subsequent space-time interface configurations.

Journal Article↗

PubMed2004

Global simulation for laser-driven MeV electrons in fast ignition.

A comprehensive examination of the interaction of a picosecond-long ignition pulse on high-density (40 times critical density) pellets using a two-dimensional particle-in-cell model is described. The global geometry consists of a 50 mum diameter pellet surrounded by a corona which is isolated by a vacuum region from the boundary. For cone-attached targets, as much as 67% of the incident laser energy is absorbed with 12% sent forward as fast electrons in a 23 degrees cone. The current filaments are driven by the Weibel instability of the forward-going fast electron flux and its return current with the ions playing an important role of neutralizing the space charge. No global current filament coalescence has been observed. The electron distribution function obeys a power law, which begins at E approximately 0.2 MeV and falls off as E-(2-3).

Journal Article↗

PubMed2005

Reviewing models of auxin canalization in the context of leaf vein pattern formation in Arabidopsis.

In both plants and animals vein networks play an essential role in transporting nutrients. In plants veins may also provide mechanical support. The mechanism by which vein patterns are formed in a developing leaf remains largely unresolved. According to the canalization hypothesis, a signal inducing vein differentiation is transported in a polar manner and is channeled into narrow strands. Since inhibition of auxin transport affects venation patterns, auxin is likely to be part of the signal involved. However, it is not clear whether the canalization hypothesis, initially formulated over 25 years ago, is compatible with recent experimental data. In this paper we focus on three aspects of this question, and show that: (i) canalization models can account for an acropetal development of the midvein if vein formation is sink-driven; (ii) canalization models are in agreement with venation patterns resulting from inhibited auxin transport and (iii) loops and discontinuous venation patterns can be obtained assuming proper spacing of discrete auxin sources.

Arabidopsis↗