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At least 199 records · Page 11Linked to original sources

Prescheduling graphic displays for optimal cancer therapies to reveal possible tumor regression or stabilization.

The paper describes an adaptive control approach to the problem of the treatment of solid tumors. The evolution with time t of the state of a tumor is modelled by a two-compartment system, governed by two differential equations forming an autonomous system under therapy control u, (formula; see text) where y1 and y2 are the number of proliferating and nonproliferating cells, respectively. The output is analyzed in the phase plane y1y2. The control problem is that of restricting the tumor state to a predetermined region of the plane by selecting a suitable change in therapy control u, e.g., modality and dosage, when the state solution intersects the boundary of this region and the ratio y1/y2 of proliferating to nonproliferating cells is displayed together with an elapsed time scale. Then, consequent selection of a suitable therapeutic sequence may be assisted by the use of a data base as part of an expert system. The process is repeated at each intersection of the prescribed boundary. Such sequences may lead to stabilization of the system through the appearance on a computer display screen of a stable equilibrium point or a limit cycle.

Cell Division↗

Rayleigh-Benard convection in a vertically oscillated fluid layer

We report on the first quantitative observations of convection in a fluid layer driven by both heating from below and vertical sinusoidal oscillation. Just above onset, convection patterns are modulated either harmonically or subharmonically to the drive frequency. Single-frequency patterns exhibit nearly solid-body rotations with harmonic and subharmonic states always rotating in opposite directions. Flows with both harmonic and subharmonic responses are found near a codimension-two point, yielding novel coexisting patterns with symmetries not found in either single-frequency states. Predictions from linear stability analysis of the onset Rayleigh and wave numbers compare well with experiment, and phase boundaries for coexisting patterns track single-frequency marginal stability curves.

Journal Article↗

Phase locking in Josephson ladders and the discrete sine-Gordon equation: the effects of boundary conditions and current-induced magnetic fields.

We report on the stability of phase-locked solutions to ladder arrays of underdamped Josephson junctions under both periodic and open boundary conditions and in the presence of current-induced magnetic fields. We calculate the Floquet exponents based on the resistively and capacitively shunted junction (RCSJ) model, as well as on a simplified model of the ladder that leads to a discrete sine-Gordon (DSG) equation for the horizontal, current-biased junctions. In the case of zero induced magnetic fields, we find the DSG equation (commonly applied to parallel arrays) appreciably overestimates the exponents of the full ladder in the overdamped regime (corresponding to the limit of small junction capacitance, beta(c)), and that difference physically results from differing spectra for small-amplitude phase oscillations of the DSG and RCSJ equations. mutual inductance between plaquettes is included we find there are ranges of values for the mutual inductance for which the ladder is in fact unstable. To understand the cause of the observed instabilities, it is crucial to consider the behavior of the vertical junctions.

Journal Article↗

Effect of delay on the boundary of the basin of attraction in a self-excited single graded-response neuron.

Little attention has been paid in the past to the effects of interunit transmission delays (representing axonal and synaptic delays) on the boundary of the basin of attraction of stable equilibrium points in neural networks. As a first step toward a better understanding of the influence of delay, we study the dynamics of a single graded-response neuron with a delayed excitatory self-connection. The behavior of this system is representative of that of a family of networks composed of graded-response neurons in which most trajectories converge to stable equilibrium points for any delay value. It is shown that changing the delay modifies the "location" of the boundary of the basin of attraction of the stable equilibrium points without affecting the stability of the equilibria. The dynamics of trajectories on the boundary are also delay dependent and influence the transient regime of trajectories within the adjacent basins. Our results suggest that when dealing with networks with delay, it is important to study not only the effect of the delay on the asymptotic convergence of the system but also on the boundary of the basins of attraction of the equilibria.

Animals↗

Structural analysis of ternary complexes of Escherichia coli RNA polymerase. Deoxyribonuclease I footprinting of defined complexes.

The structure and properties of ternary complexes of RNA polymerase are of central importance in understanding the mechanisms of transcriptional elongation and termination, and the regulation of these primary steps in gene expression. However, there has been no systematic study of the structure and properties of such complexes along a single transcription unit. Recently, we have described the isolation of a collection of halted ternary complexes of Escherichia coli RNA polymerase bearing transcripts from 11 to 35 nucleotides in length along two different transcription units (accompanying paper). Here, we report structural studies of these complexes using DNase I footprinting. Surprisingly, nearly all of the different ternary complexes have distinctly different footprints along the two DNA strands, and the position of the footprint relative to the 3' end of the transcript also varies for most complexes. Halted complexes bearing transcripts of comparable size do not have identical footprints; hence, DNA sequence as well as transcript length plays a role in determining the size and position of the footprint. These differences in structure are consistent with our earlier findings that ternary complexes can differ considerably in stability and gel mobility. The downstream boundary of the RNA polymerase in ternary complexes does not move forward regularly as successive nucleotide residues are added to the RNA chain. In contrast, the upstream boundary moves forward more or less in concert with the movement of the 3' terminus of the transcript. These factors lead to a general compression of the overall footprint as transcription proceeds, together with a steady movement of the 3' terminus of the RNA toward the downstream boundary of the polymerase. Ultimately, after the length of the RNA transcript has increased from eight to ten nucleotides, the downstream boundary of the complex is found to move downstream along the DNA, suggesting a translocation event. We suggest that RNA chain elongation, like RNA chain initiation, may involve a saltatory process in which net translocation of the complex along the DNA occurs only after addition of a number of ribonucleotides to the RNA chain.

Base Sequence↗

Cross-sectional estimation of Babesia bovis antibody prevalence in an area of Argentina used for extensive cattle breeding as an aid to control babesiosis.

The prevalence of Babesia bovis antibodies was estimated by using an ELISA (98% sensitivity and 95% specificity). Sera were obtained from 165 calves (mean age and standard deviation: 9.7 +/- 2.7 months) from an area in Argentina known to be unfavourable for the development of the vector tick, Boophilus microplus. The area comprised about 300,000 ha used for cattle breeding. The cattle population of 55,000 included 12,000 cattle under 1 year of age. Cattle were maintained mainly on natural grasses in communal lands. The true prevalence of antibodies to Babesia bovis was 12.2% with a confidence interval of 7.6% to 18.2%, and an inoculation rate (h; daily probability of infection) of 0.0004. This confidence interval has its lower boundary in the area of endemic stability due to low h of Babesia bovis by the vector tick and the upper limit in the area of endemic instability. This type of analysis could help to decide the implementation of preventive measures (e.g. vaccination) rationally, even in remote areas (such as the one of the present study) with an extensive cattle industry.

Animals↗

Chiron3D: an interpretable deep learning framework for understanding the DNA code of chromatin looping.

MOTIVATION: Three-dimensional folding of the genome into structures such as chromatin loops is essential for gene regulation. Current experimental methods for mapping these structures, like Hi-C and HiChIP, are labor-intensive and require repeated assays to test hypothesized mutation effects. This motivates the need for predictive approaches that reveal the sequence determinants of chromatin loops. RESULTS: In this work, we present a novel and interpretable computational pipeline for predicting CTCF-mediated chromatin loops. We propose Chiron3D, a DNA-only model trained in a cell-type specific manner to predict CTCF HiChIP contact maps. By leveraging pre-trained embeddings from a foundation model, our approach is competitive with baselines that take CTCF ChIP-seq as additional input, while enabling nucleotide-level attribution to the input DNA sequence. Using our framework, we provide likely mechanistic insights into the physical control of loop dynamics. Specifically, we find that the strength of the loop extrusion anchorage site is largely governed by the amount and binding affinity of CTCF sites at the boundaries. Furthermore, we reveal that loop stability is regulated by the amount of intra-loop CTCF binding sites, where fewer intra-loop sites are associated with greater loop stability. Using targeted, single-nucleotide edit simulations with Chiron3D, we show that both loop strength and stability can be precisely controlled. Together, these results provide novel mechanistic insights into the physical control of genome organization and highlight the potential of decoding the DNA sequence logic in silico. AVAILABILITY: The Chiron3D pipeline is made available at https://github.com/BoevaLab/Chiron3D.

Chromatin↗

Dynamical models for dissipative localized waves of the complex Ginzburg-Landau equation.

Finite-dimensional dynamical models for solitons of the cubic-quintic complex Ginzburg-Landau equation (CGLE) are derived. The models describe the evolution of the pulse parameters, such as the maximum amplitude, pulse width, and chirp. A clear correspondence between attractors of the finite-dimensional dynamical systems and localized waves of the continuous dissipative system is demonstrated. It is shown that stationary solitons of the CGLE correspond to fixed points, while pulsating solitons are associated with stable limit cycles. The models show that a transformation from a stationary soliton to a pulsating soliton is the result of a Hopf bifurcation in the reduced dynamical system. The appearance of moving fronts (kinks) in the CGLE is related to the loss of stability of the limit cycles. Bifurcation boundaries and pulse behavior in the regions between the boundaries, for a wide range of system parameters, are found from analysis of the reduced dynamical models. We also provide a comparison between various models and their correspondence to the exact results.

Journal Article↗

The mechanism of diamond nucleation from energetic species.

A model for diamond nucleation by energetic species (for example, bias-enhanced nucleation) is proposed. It involves spontaneous bulk nucleation of a diamond embryo cluster in a dense, amorphous carbon hydrogenated matrix; stabilization of the cluster by favorable boundary conditions of nucleation sites and hydrogen termination; and ion bombardment-induced growth through a preferential displacement mechanism. The model is substantiated by density functional tight-binding molecular dynamics simulations and an experimental study of the structure of bias-enhanced and ion beam-nucleated films. The model is also applicable to the nucleation of other materials by energetic species, such as cubic boron nitride.

Journal Article↗

Structure of the 70S ribosome complexed with mRNA and tRNA.

The crystal structure of the bacterial 70S ribosome refined to 2.8 angstrom resolution reveals atomic details of its interactions with messenger RNA (mRNA) and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that demarcates the boundary between A and P sites, which is potentially important to prevent slippage of mRNA. Metal ions also stabilize the intersubunit interface. The interactions of E-site tRNA with the 50S subunit have both similarities and differences compared to those in the archaeal ribosome. The structure also rationalizes much biochemical and genetic data on translation.

Anticodon↗

"Mixing" as an ethnoetiology of HIV/AIDS in Malaysia's multinational factories.

Minah Karan, the stigmatizing label appended to Malay factory women in the 1980s, signaled a dangerous female sexuality that risked spreading beyond the factory gates and infecting Malaysia's idea(l)s of its traditional kampung culture. This article narrates how Minah Karan, as the former antihero of development, was reconstituted in the 1990s, with the government's labeling of factories as "high-risk settings" for HIV/AIDS. This is an ethnoetiology based not on any evidential epidemiological data but on the racial and gendered "mixing" that transpires behind factory walls: a fear that the "mixing of the sexes" means ipso facto "sexual mixing" among the races. The article demonstrates how importation of the high-risk label articulates at the local level the new and contested linkages, economic, religious, and scientific, constitutive of globalization. The pragmatic nature and imperatives of this high-risk process are discerned in factory women's accounts of how they negotiate the interactional imperatives of factory work, because transnational structures of productivity violate the social boundaries that have long connoted political stability, moral integrity, ethnic community, and individual safety. The article concludes by questioning whether ethnoetiologies, especially when they concern sexual networks, become social etiologies, because this would locate ethnoetiologies as central to conventional public health praxis rather than as ethnographic exotica in the margins.

Ethnicity↗

[Correlations of the indicators of biochemical composition and physico-chemical properties of the bile in chronic cholecystitis].

The study of the factors relevant to the bile colloid stability in aggravation of calculous or ++non-calculous cholecystitis demonstrated changes in aggregative-kinetic stability of bile presenting with low boundary of the phase transition, electrokinetic potential, mass and growing size of macromolecular compounds. This is much coupled with high bile levels of protein, calcium and iron which exhibited mutually potentiating effect. At the same time, hydrolysis of protein-containing bile components +determined by the increment of amine and sulfhydryl groups evidences for colloid destabilizing active role of calcium and iron. In view of this finding elevated concentration of iron and calcium in exacerbations of cholecystitis may have both diagnostic significance and be indicator of the role of inflammation in lithogenesis.

Bile↗

Dynamics and equilibria of nucleosomes at elevated ionic strength.

We have prepared chicken erythrocyte nucleosomes lacking proteins other than the inner histones and containing long DNA. Our nucleosomes' DNA has mean length +/- SD = 190 +/- 15 base pairs. No DNA less than 155 base pairs is present. Nucleosome stability in salt was examined by boundary and band sedimentation and by particle gel electrophoresis. We find the following. (i) A second species is slowly generated by treatment with salt. This species sediments with S20,w = 5.5 S (as does purified mononucleosomal DNA), is not associated with histones, and electrophoretically migrates as mononucleosomal DNA. We conclude it is free DNA. Thus, salt causes nucleosomes to dissociate, independently of either noncore proteins, or of any nucleosome population with DNA less than 146 base pairs. (ii) Dissociation is reversible, and is enhanced by nucleosome dilution. Thus, it appears to follow the law of mass action. (iii) The equilibrium extent of dissociation increases with salt. A second effect of salt is a fast, reversible 10% decrease in S20,w of the nucleosomes left intact. From hydrodynamic calculations, this is consistent with either a slight unfolding of the entire nucleosome, or an unbinding of the terminal DNA regions from the histone core.

Animals↗

Exocyclic amine of the conserved G.U pair at the cleavage site of the Tetrahymena ribozyme contributes to 5'-splice site selection and transition state stabilization.

A phylogenetically conserved guanine.uracil (G.U) pair defines the 5'-exon/intron boundary of precursor RNAs containing group I introns. In this wobble base pair, the G forms two hydrogen bonds with U in a base pairing geometry shifted from that of a canonical Watson-Crick pair. On the basis of thermodynamic measurements of synthetic base pair analogs (inosine, diaminopurine riboside, guanosine, or adenosine paired with U, C, or isocytidine) in place of the G.U pair, we have previously reported that the N2 exocyclic amine of the G is important for docking the 5'-exon into the active site of the Tetrahymena ribozyme [Strobel, S. A., & Cech, T. R. (1995) Science 267, 675-679]. Here we describe kinetic characterization of ribozyme-substrate combinations containing the same series of analogs. By measuring the rate constants of 5'-exon miscleavage (cleavage at incorrect phosphates), we demonstrate that the 5'-exon/intron boundary is primarily defined by the exocyclic amine of the G. The amine makes its contribution (2.5 kcal.mol-1) in the context of all three wobble pairs tested but fails to make a significant contribution (< 0.8 kcal.mol-1) when presented in a Watson-Crick base pairing geometry. We also demonstrate that the exocyclic amine makes a modest contribution to chemical transition state stabilization (1.0 kcal.mol-1 relative to an inosine-U pair). The majority of this transition state contribution (0.7 kcal.mol-1) is independent of that contributed by the 2'-hydroxyl of the neighboring U. This argues against the model in which substantial transition state stabilization is derived from a water molecule bridging between the exocyclic amine of G and the 2'-hydroxyl of U. Instead it suggests that the tertiary interaction between the exocyclic amine and its hydrogen bonding partner in the active site is slightly improved during the chemical transition. We conclude that the exocyclic amine of G is the primary contributor to many characteristics of reactivity that have been ascribed to the conserved G.U pair, including stabilization of the chemical transition state and definition of the 5'-exon/intron boundary.

Animals↗

Traveling waves in rotating Rayleigh-Bénard convection.

A combined analytical, numerical, and experimental study of the traveling-wave wall mode in rotating Rayleigh-Bénard convection is presented. No-slip top and bottom boundary conditions are used for the numerical computation of the linear stability, and the coefficients of the linear complex Ginzburg-Landau equation are then computed for various rotation rates. Numerical results for the no-slip boundary conditions are compared with free-slip calculations and with experimental data, and detailed comparison is made at a dimensionless rotation rate Omega=274. It is found that the inclusion of the more realistic no-slip boundary conditions for the top and bottom surfaces brings the numerical linear stability analysis into better agreement with the experimental data compared with results using free-slip top/bottom boundary conditions. Some remaining discrepancies may be accounted for by the finite conductivity of the sidewall boundaries.

Journal Article↗

Long-wave theory for a new convective instability with exponential growth normal to the wall.

A linear stability theory is presented for the boundary-layer flow produced by an infinite disc rotating at constant angular velocity in otherwise undisturbed fluid. The theory is developed in the limit of long waves and when the effects of viscosity on the waves can be neglected. This is the parameter regime recently identified by the author in a numerical stability investigation where a curious new type of instability was found in which disturbances propagate and grow exponentially in the direction normal to the disc, (i.e. the growth takes place in a region of zero mean shear). The theory describes the mechanisms controlling the instability, the role and location of critical points, and presents a saddle-point analysis describing the large-time evolution of a wave packet in frames of reference moving normal to the disc. The theory also shows that the previously obtained numerical solutions for numerically large wavelengths do indeed lie in the asymptotic long-wave regime, and so the behaviour and mechanisms described here may apply to a number of cross-flow instability problems.

Journal Article↗

Wear of retrieved cemented polyethylene acetabula with alumina femoral heads.

Four yttrium-stabilized alumina ceramic-on-polyethylene articulations obtained from patients who were undergoing revision surgery for sepsis (3) or recurrent dislocation (I) between 34 and 73 months were evaluated to assess their in vivo wear performance. The annual volumetric wear of the acetabular components determined directly by a fluid displacement method ranged from 58 to 140 mm3/y. Scanning electron microscope examination of these four ceramic heads revealed similar surface damage in all cases from a variety of causes. These included differential granular wear (alumina grains and yttrium-stabilized alumina grains at different depths), multidirectional scratches with heaped up boundaries, and incompletely sintered grains, as well as the formation of craters and separation of grain boundaries. The femoral heads in this small series of revision cases show that yttrium-stabilized alumina ceramic heads may develop surface irregularities from either manufacturing processes or in vivo use. The wear rates of this type of alumina-on-polyethylene articulation up to the time of revision were not substantially different from those found in other metal-on-polyethylene articulations retrieved at revision surgery.

Acetabulum↗

The sharkskin instability of polymer melt flows.

Flows of polymeric liquids undergo instabilities whose origins are quite different from those of Newtonian flows, due to their elastic character and the complexity of the fluid/solid boundary condition. This article reviews recent studies of one such instability, the sharkskin phenomenon observed during extrusion of many linear polymers. Key experimental observations are summarized; one important fact that has become clear is the importance of the interaction between the molten polymer and the solid walls of the flow channel, especially near the contact line at the exit of the channel. Recent developments in understanding the relationship between wall slip and disentanglement of wall-adsorbed polymers from the bulk flow are briefly described, and putative heuristic mechanisms relating the instability to slip and contact line motion are presented. Finally, we review mathematical analyses of the stability of viscoelastic shear flows with slip boundary conditions. Some recent analyses yield instability predictions that are consistent with experiments, but further work is required to discriminate between the various mechanisms that have been proposed. (c) 1999 American Institute of Physics.

Journal Article↗