361 research outputs found
Human Chromosomes: Evaluation of Processing Techniques for Scanning Electron Microscopy
Methods for scanning electron microscopy (SEM) of chromosomes have been developed in the last two decades. Technical limitations in the study of human chromosomes, however, have hindered the routine use of SEM in clinical and experimental human cytogenetics. We compared different methodologies, including metal impregnation, air drying and specimen coating. SEM preparation of human chromosomes in which osmium impregnation is mediated by tannic acid, yielded more reproducible results when compared with osmium impregnation protocols previously described. The level of osmium impregnation was systematically evaluated by imaging chromosomes in the backscattering mode. Critical point drying and a light gold-palladium coating were essential for appropriate secondary electron imaging of chromosomes. With this method, and in a preliminary quantitative analysis, we show that our SEM technique is mere sensitive than light microscopy for the detection of aphidicolin-induced fragile sites. This technical approach is useful for chromosomal studies requiring resolution higher than that obtained by light microscopy. Also, it allows the use of clinical and archival chromosomal samples prepared by routine cytogenetic techniques
Evolutionary Trajectories are Contingent on Mitonuclear Interactions
Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the mitochondrial and nuclear genomes. The fitness of eukaryotic organisms depends on a tight collaboration between both genomes. In the face of an elevated rate of evolution in mtDNA, current models predict that the maintenance of mitonuclear compatibility relies on compensatory evolution of the nuclear genome. Mitonuclear interactions would therefore exert an influence on evolutionary trajectories. One prediction from this model is that the same nuclear genome evolving with different mitochondrial haplotypes would follow distinct molecular paths toward higher fitness. To test this prediction, we submitted 1,344 populations derived from 7 mitonuclear genotypes of Saccharomyces cerevisiae to >300 generations of experimental evolution in conditions that either select for a mitochondrial function or do not strictly require respiration for survival. Performing high-throughput phenotyping and whole-genome sequencing on independently evolved individuals, we identified numerous examples of gene-level evolutionary convergence among populations with the same mitonuclear background. Phenotypic and genotypic data on strains derived from this evolution experiment identify the nuclear genome and the environment as the main determinants of evolutionary divergence, but also show a modulating role for the mitochondrial genome exerted both directly and via interactions with the two other components. We finally recapitulated a subset of prominent loss-of-function alleles in the ancestral backgrounds and confirmed a generalized pattern of mitonuclear-specific and highly epistatic fitness effects. Together, these results demonstrate how mitonuclear interactions can dictate evolutionary divergence of populations with identical starting nuclear genotypes
Towards Multidisciplinary HIV-Cure Research: Integrating Social Science with Biomedical Research
The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multi-disciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community
A shadowing problem in the detection of overlapping communities: lifting the resolution limit through a cascading procedure
Community detection is the process of assigning nodes and links in
significant communities (e.g. clusters, function modules) and its development
has led to a better understanding of complex networks. When applied to sizable
networks, we argue that most detection algorithms correctly identify prominent
communities, but fail to do so across multiple scales. As a result, a
significant fraction of the network is left uncharted. We show that this
problem stems from larger or denser communities overshadowing smaller or
sparser ones, and that this effect accounts for most of the undetected
communities and unassigned links. We propose a generic cascading approach to
community detection that circumvents the problem. Using real and artificial
network datasets with three widely used community detection algorithms, we show
how a simple cascading procedure allows for the detection of the missing
communities. This work highlights a new detection limit of community structure,
and we hope that our approach can inspire better community detection
algorithms.Comment: 14 pages, 12 figures + supporting information (5 pages, 6 tables, 3
figures
Phase-field approach to heterogeneous nucleation
We consider the problem of heterogeneous nucleation and growth. The system is
described by a phase field model in which the temperature is included through
thermal noise. We show that this phase field approach is suitable to describe
homogeneous as well as heterogeneous nucleation starting from several general
hypotheses. Thus we can investigate the influence of grain boundaries,
localized impurities, or any general kind of imperfections in a systematic way.
We also put forward the applicability of our model to study other physical
situations such as island formation, amorphous crystallization, or
recrystallization.Comment: 8 pages including 7 figures. Accepted for publication in Physical
Review
Multi-stakeholder consensus on a target product profile for an HIV cure
Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures
Theory and applications of atomic and ionic polarizabilities
Atomic polarization phenomena impinge upon a number of areas and processes in
physics. The dielectric constant and refractive index of any gas are examples
of macroscopic properties that are largely determined by the dipole
polarizability. When it comes to microscopic phenomena, the existence of
alkaline-earth anions and the recently discovered ability of positrons to bind
to many atoms are predominantly due to the polarization interaction. An
imperfect knowledge of atomic polarizabilities is presently looming as the
largest source of uncertainty in the new generation of optical frequency
standards. Accurate polarizabilities for the group I and II atoms and ions of
the periodic table have recently become available by a variety of techniques.
These include refined many-body perturbation theory and coupled-cluster
calculations sometimes combined with precise experimental data for selected
transitions, microwave spectroscopy of Rydberg atoms and ions, refractive index
measurements in microwave cavities, ab initio calculations of atomic structures
using explicitly correlated wave functions, interferometry with atom beams, and
velocity changes of laser cooled atoms induced by an electric field. This
review examines existing theoretical methods of determining atomic and ionic
polarizabilities, and discusses their relevance to various applications with
particular emphasis on cold-atom physics and the metrology of atomic frequency
standards.Comment: Review paper, 44 page
Multi-stakeholder consensus on a target product profile for an HIV cure
Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures
Imbibition in Disordered Media
The physics of liquids in porous media gives rise to many interesting
phenomena, including imbibition where a viscous fluid displaces a less viscous
one. Here we discuss the theoretical and experimental progress made in recent
years in this field. The emphasis is on an interfacial description, akin to the
focus of a statistical physics approach. Coarse-grained equations of motion
have been recently presented in the literature. These contain terms that take
into account the pertinent features of imbibition: non-locality and the
quenched noise that arises from the random environment, fluctuations of the
fluid flow and capillary forces. The theoretical progress has highlighted the
presence of intrinsic length-scales that invalidate scale invariance often
assumed to be present in kinetic roughening processes such as that of a
two-phase boundary in liquid penetration. Another important fact is that the
macroscopic fluid flow, the kinetic roughening properties, and the effective
noise in the problem are all coupled. Many possible deviations from simple
scaling behaviour exist, and we outline the experimental evidence. Finally,
prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe
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