460 research outputs found
Propagation of charged particle waves in a uniform magnetic field
This paper considers the probability density and current distributions
generated by a point-like, isotropic source of monoenergetic charges embedded
into a uniform magnetic field environment. Electron sources of this kind have
been realized in recent photodetachment microscopy experiments. Unlike the
total photocurrent cross section, which is largely understood, the spatial
profiles of charge and current emitted by the source display an unexpected
hierarchy of complex patterns, even though the distributions, apart from
scaling, depend only on a single physical parameter. We examine the electron
dynamics both by solving the quantum problem, i. e., finding the energy Green
function, and from a semiclassical perspective based on the simple cyclotron
orbits followed by the electron. Simulations suggest that the semiclassical
method, which involves here interference between an infinite set of paths,
faithfully reproduces the features observed in the quantum solution, even in
extreme circumstances, and lends itself to an interpretation of some (though
not all) of the rich structure exhibited in this simple problem.Comment: 39 pages, 16 figure
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Pairing of Competitive and Topologically Distinct Regulatory Modules Enhances Patterned Gene Expression
Biological networks are inherently modular, yet little is known about how modules are assembled to enable coordinated and complex functions. We used RNAi and time series, whole-genome microarray analyses to systematically perturb and characterize components of a Caenorhabditis elegans lineage-specific transcriptional regulatory network. These data are supported by selected reporter gene analyses and comprehensive yeast one-hybrid and promoter sequence analyses. Based on these results, we define and characterize two modules composed of muscle- and epidermal-specifying transcription factors that function together within a single cell lineage to robustly specify multiple cell types. The expression of these two modules, although positively regulated by a common factor, is reliably segregated among daughter cells. Our analyses indicate that these modules repress each other, and we propose that this cross-inhibition coupled with their relative time of induction function to enhance the initial asymmetry in their expression patterns, thus leading to the observed invariant gene expression patterns and cell lineage. The coupling of asynchronous and topologically distinct modules may be a general principle of module assembly that functions to potentiate genetic switches.Molecular and Cellular Biolog
Evaluation of adapted parent training for challenging behaviour in pre-school children with moderate to severe intellectual developmental disabilities: A randomised controlled trial
Copyright: \ua9 2024 Royston et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. OBJECTIVES: There is limited evidence on the effectiveness of parenting interventions to improve disruptive behaviour in children with intellectual developmental disabilities. This clinical trial evaluated whether an adapted group parenting intervention for preschool children with intellectual developmental disabilities who display challenging behaviour is superior to treatment as usual in England. STUDY DESIGN: 261 children aged 30-59 months with moderate to severe intellectual developmental disabilities and challenging behaviour were randomised to either the intervention (Stepping Stones Triple P) and treatment as usual or treatment as usual alone. The primary outcome was the parent-rated Child Behaviour Checklist at 52 weeks after randomisation. A health economic evaluation was also completed. RESULTS: We found no significant difference between arms on the primary outcome (mean difference -4.23; 95% CI: -9.99 to 1.53; p = 0.147). However, a subgroup analysis suggests the intervention was effective for participants randomised before the COVID-19 pandemic (mean difference -7.12; 95% CI: -13.44 to -0.81; p = 0.046). Furthermore, a complier average causal effects analysis (mean difference -11.53; 95% CI: -26.97 to 3.91; p = 0.143) suggests the intervention requires participants to receive a sufficient intervention dose. The intervention generated statistically significant cost savings (-\ua31,057.88; 95% CI -\ua33,218.6 to -\ua346.67) but the mean point estimate in Quality Adjusted Life Years was similar in both groups. CONCLUSION: This study did not find an effect of the intervention on reducing challenging behaviour, but this may have been influenced by problems with engagement. The intervention could be considered by services as an early intervention if families are supported to attend, especially given its low cost
Systems biology via redescription and ontologies (I): finding phase changes with applications to malaria temporal data
Biological systems are complex and often composed of many subtly interacting components. Furthermore, such systems evolve through time and, as the underlying biology executes its genetic program, the relationships between components change and undergo dynamic reorganization. Characterizing these relationships precisely is a challenging task, but one that must be undertaken if we are to understand these systems in sufficient detail. One set of tools that may prove useful are the formal principles of model building and checking, which could allow the biologist to frame these inherently temporal questions in a sufficiently rigorous framework. In response to these challenges, GOALIE (Gene ontology algorithmic logic and information extractor) was developed and has been successfully employed in the analysis of high throughput biological data (e.g. time-course gene-expression microarray data and neural spike train recordings). The method has applications to a wide variety of temporal data, indeed any data for which there exist ontological descriptions. This paper describes the algorithms behind GOALIE and its use in the study of the Intraerythrocytic Developmental Cycle (IDC) of Plasmodium falciparum, the parasite responsible for a deadly form of chloroquine resistant malaria. We focus in particular on the problem of finding phase changes, times of reorganization of transcriptional control
On reminder effects, drop-outs and dominance: evidence from an online experiment on charitable giving
We present the results of an experiment that (a) shows the usefulness of screening out drop-outs and (b) tests whether different methods of payment and reminder intervals affect charitable giving. Following a lab session, participants could make online donations to charity for a total duration of three months. Our procedure justifying the exclusion of drop-outs consists in requiring participants to collect payments in person flexibly and as known in advance and as highlighted to them later. Our interpretation is that participants who failed to collect their positive payments under these circumstances are likely not to satisfy dominance. If we restrict the sample to subjects who did not drop out, but not otherwise, reminders significantly increase the overall amount of charitable giving. We also find that weekly reminders are no more effective than monthly reminders in increasing charitable giving, and that, in our three months duration experiment, standing orders do not increase giving relative to one-off donations
The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket
P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism
Ballistic matter waves with angular momentum: Exact solutions and applications
An alternative description of quantum scattering processes rests on
inhomogeneous terms amended to the Schroedinger equation. We detail the
structure of sources that give rise to multipole scattering waves of definite
angular momentum, and introduce pointlike multipole sources as their limiting
case. Partial wave theory is recovered for freely propagating particles. We
obtain novel results for ballistic scattering in an external uniform force
field, where we provide analytical solutions for both the scattering waves and
the integrated particle flux. Our theory directly applies to p-wave
photodetachment in an electric field. Furthermore, illustrating the effects of
extended sources, we predict some properties of vortex-bearing atom laser beams
outcoupled from a rotating Bose-Einstein condensate under the influence of
gravity.Comment: 42 pages, 8 figures, extended version including photodetachment and
semiclassical theor
NIBBS-Search for Fast and Accurate Prediction of Phenotype-Biased Metabolic Systems
Understanding of genotype-phenotype associations is important not only for furthering our knowledge on internal cellular processes, but also essential for providing the foundation necessary for genetic engineering of microorganisms for industrial use (e.g., production of bioenergy or biofuels). However, genotype-phenotype associations alone do not provide enough information to alter an organism's genome to either suppress or exhibit a phenotype. It is important to look at the phenotype-related genes in the context of the genome-scale network to understand how the genes interact with other genes in the organism. Identification of metabolic subsystems involved in the expression of the phenotype is one way of placing the phenotype-related genes in the context of the entire network. A metabolic system refers to a metabolic network subgraph; nodes are compounds and edges labels are the enzymes that catalyze the reaction. The metabolic subsystem could be part of a single metabolic pathway or span parts of multiple pathways. Arguably, comparative genome-scale metabolic network analysis is a promising strategy to identify these phenotype-related metabolic subsystems. Network Instance-Based Biased Subgraph Search (NIBBS) is a graph-theoretic method for genome-scale metabolic network comparative analysis that can identify metabolic systems that are statistically biased toward phenotype-expressing organismal networks. We set up experiments with target phenotypes like hydrogen production, TCA expression, and acid-tolerance. We show via extensive literature search that some of the resulting metabolic subsystems are indeed phenotype-related and formulate hypotheses for other systems in terms of their role in phenotype expression. NIBBS is also orders of magnitude faster than MULE, one of the most efficient maximal frequent subgraph mining algorithms that could be adjusted for this problem. Also, the set of phenotype-biased metabolic systems output by NIBBS comes very close to the set of phenotype-biased subgraphs output by an exact maximally-biased subgraph enumeration algorithm ( MBS-Enum ). The code (NIBBS and the module to visualize the identified subsystems) is available at http://freescience.org/cs/NIBBS
Machine Learning in Automated Text Categorization
The automated categorization (or classification) of texts into predefined
categories has witnessed a booming interest in the last ten years, due to the
increased availability of documents in digital form and the ensuing need to
organize them. In the research community the dominant approach to this problem
is based on machine learning techniques: a general inductive process
automatically builds a classifier by learning, from a set of preclassified
documents, the characteristics of the categories. The advantages of this
approach over the knowledge engineering approach (consisting in the manual
definition of a classifier by domain experts) are a very good effectiveness,
considerable savings in terms of expert manpower, and straightforward
portability to different domains. This survey discusses the main approaches to
text categorization that fall within the machine learning paradigm. We will
discuss in detail issues pertaining to three different problems, namely
document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey
Pairwise maximum entropy models for studying large biological systems: when they can and when they can't work
One of the most critical problems we face in the study of biological systems
is building accurate statistical descriptions of them. This problem has been
particularly challenging because biological systems typically contain large
numbers of interacting elements, which precludes the use of standard brute
force approaches. Recently, though, several groups have reported that there may
be an alternate strategy. The reports show that reliable statistical models can
be built without knowledge of all the interactions in a system; instead,
pairwise interactions can suffice. These findings, however, are based on the
analysis of small subsystems. Here we ask whether the observations will
generalize to systems of realistic size, that is, whether pairwise models will
provide reliable descriptions of true biological systems. Our results show
that, in most cases, they will not. The reason is that there is a crossover in
the predictive power of pairwise models: If the size of the subsystem is below
the crossover point, then the results have no predictive power for large
systems. If the size is above the crossover point, the results do have
predictive power. This work thus provides a general framework for determining
the extent to which pairwise models can be used to predict the behavior of
whole biological systems. Applied to neural data, the size of most systems
studied so far is below the crossover point
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