Biomedical subjects

David G Grier

Publications and source records attributed to David G Grier.

At least 19 recordsLinked to original sources

PubMed2006

Colloidal electroconvection in a thin horizontal cell. II. Bulk electroconvection of water during parallel-plate electrolysis.

We recently have reported [J. Chem. Phys. 122, 164701 (2005)] a family of electroconvective patterns that arise when charge-stabilized colloidal dispersions are driven by constant (dc) vertical electric fields. Competition between gravity and electrokinetic forces acting on the individual spheres in this system leads to the formation of highly organized convective instabilities involving hundreds of spheres. Here, we report a distinct class of electroconvective patterns that emerge in confined aqueous dispersions at higher biases. These qualitatively resemble the honeycomb and labyrinthine patterns formed during thermally driven Rayleigh-Benard convection, but arise from a distinct mechanism. Unlike the localized colloidal electroconvective patterns observed at lower biases, moreover, these system-spanning patterns form even without dispersed colloidal particles. Rather, they appear to result from an underlying electroconvective instability during electrolysis in the parallel plate geometry. This contrasts with recent theoretical results suggesting that simple electrolytes are linearly stable against electroconvection.

Journal Article↗

PubMed2006

Projecting extended optical traps with shape-phase holography.

We describe a method for projecting single-beam optical traps whose potential energy wells are extended along one-dimensional curves. This technique exploits shape-phase holography in which computer-generated phase-only diffractive optical elements are used to implement complex and amplitude-only holograms. The resulting optical traps can have specified intensity and phase profiles along their lengths and can extend along curves in three dimensions. We demonstrate the extended traps' operation and characterize their potential energy profiles through digital video microscopy of trapped colloidal spheres.

Journal Article↗

PubMed2006

Optical traps with geometric aberrations.

We assess the influence of geometric aberrations on the in-plane performance of optical traps by studying the dynamics of trapped colloidal spheres in deliberately distorted holographic optical tweezers. The lateral stiffness of the traps turns out to be insensitive to moderate amounts of coma, astigmatism, and spherical aberration. Moreover holographic aberration correction enables us to compensate inherent shortcomings in the optical train, thereby adaptively improving its performance. We also demonstrate the effects of geometric aberrations on the intensity profiles of optical vortices, whose readily measured deformations suggest a method for rapidly estimating and correcting geometric aberrations in holographic trapping systems.

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PubMed2006

Giant colloidal diffusivity on corrugated optical vortices.

A single colloidal sphere circulating around a periodically modulated optical vortex trap can enter a dynamical state in which it intermittently alternates between freely running around the ringlike optical vortex and becoming trapped in local potential energy minima. Velocity fluctuations in this randomly switching state still are characterized by a linear Einstein-like diffusion law, but with an effective diffusion coefficient that is enhanced by more than 2 orders of magnitude.

Journal Article↗

PubMed2006

Anomalous vibrational dispersion in holographically trapped colloidal arrays.

Colloidal spheres localized in an array of harmonic wells form a thermally excited, viscously damped dynamical system capable of supporting propagating elastic waves. Experimentally realized with micrometer-scale polystyrene spheres localized in a line of holographic optical traps, the hydrodynamically coupled array's behavior is quantitatively explained by a model based on the Oseen superposition approximation. The spheres' purely dissipative coupling is predicted to mediate a crossover to a regime of underdamped propagating elastic waves with uniformly negative group velocities that has yet to be verified experimentally.

Journal Article↗

PubMed2006

Holographic optical trapping.

Holographic optical tweezers use computer-generated holograms to create arbitrary three-dimensional configurations of single-beam optical traps that are useful for capturing, moving, and transforming mesoscopic objects. Through a combination of beam-splitting, mode-forming, and adaptive wavefront correction, holographic traps can exert precisely specified and characterized forces and torques on objects ranging in size from a few nanometers to hundreds of micrometers. Offering nanometer-scale spatial resolution and real-time reconfigurability, holographic optical traps provide unsurpassed access to the microscopic world and have found applications in fundamental research, manufacturing, and materials processing.

Journal Article↗

PubMed2006

HOX genes: seductive science, mysterious mechanisms.

HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life. The 39 human HOX genes are located in four clusters (A-D) on different chromosomes at 7p15, 17q21 [corrected] 12q13, and 2q31 respectively and are assumed to have arisen by duplication and divergence from a primordial homeobox gene. Disorders of limb formation, such as hand-foot-genital syndrome, have been traced to mutations in HOXA13 and HOXD13. Evolutionary conservation provides unlimited scope for experimental investigation of the functional control of the Hox gene network which is providing important insights into human disease. Chromosomal translocations involving the MLL gene, the human homologue of the Drosophila gene trithorax, create fusion genes which exhibit gain of function and are associated with aggressive leukaemias in both adults and children. To date 39 partner genes for MLL have been cloned from patients with leukaemia. Models based on specific translocations of MLL and individual HOX genes are now the subject of intense research aimed at understanding the molecular programs involved, and ultimately the design of chemotherapeutic agents for leukaemia. Investigation of the role of HOX genes in cancer has led to the concept that oncology may recapitulate ontology, a challenging postulate for experimentalists in view of the functional redundancy implicit in the HOX gene network.

Animals↗

PubMed2005

Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells.

Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell (HSC) populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program that determines self-renewal. However, this function cannot be solely attributed to Hoxb4 because Hoxb4(-/-) mice are viable and have an apparently normal HSC number. Quantitative polymerase chain reaction analysis showed that Hoxb4(-/-) c-Kit+ fetal liver cells expressed moderately higher levels of several Hoxb cluster genes than control cells, raising the possibility that normal HSC activity in Hoxb4(-/-) mice is due to a compensatory up-regulation of other Hoxb genes. In this study, we investigated the competitive repopulation potential of HSCs lacking Hoxb4 alone, or in conjunction with 8 other Hoxb genes. Our results show that Hoxb4(-/-) and Hoxb1-b9 (-/-) fetal liver cells retain full competitive repopulation potential and the ability to regenerate all myeloid and lymphoid lineages. Quantitative Hox gene expression profiling in purified c-Kit+ Hoxb1-b9(-/-) fetal liver cells revealed an interaction between the Hoxa, b, and c clusters with variation in expression levels of Hoxa4,-a11, and -c4.Together, these studies show a complex network of genetic interactions between several Hox genes in primitive hematopoietic cells and demonstrate that HSCs lacking up to 30% of the active Hox genes remain fully competent.

Animals↗

PubMed2005

Continuous MLL-ENL expression is necessary to establish a "Hox Code" and maintain immortalization of hematopoietic progenitor cells.

The t[(11;19)(p22;q23)] translocation, which gives rise to the MLL-ENL fusion protein, is commonly found in infant acute leukemias of both the myeloid and lymphoid lineage. To investigate the molecular mechanism of immortalization by MLL-ENL we established a Tet-regulatable system of MLL-ENL expression in primary hematopoietic progenitor cells. Immortalized myeloid cell lines were generated, which are dependent on continued MLL-ENL expression for their survival and proliferation. These cells either terminally differentiate or die when MLL-ENL expression is turned off with doxycycline. The expression profile of all 39 murine Hox genes was analyzed in these cells by real-time quantitative PCR. This analysis showed that loss of MLL-ENL was accompanied by a reduction in the expression of multiple Hoxa genes. By comparing these changes with Hox gene expression in cells induced to differentiate with granulocyte colony-stimulating factor, we show for the first time that reduced Hox gene expression is specific to loss of MLL-ENL and is not a consequence of differentiation. Our data also suggest that the Hox cofactor Meis-2 can substitute for Meis-1 function. Thus, MLL-ENL is required to initiate and maintain immortalization of myeloid progenitors and may contribute to leukemogenesis by aberrantly sustaining the expression of a "Hox code" consisting of Hoxa4 to Hoxa11.

Animals↗

PubMed2005

Flux reversal in a two-state symmetric optical thermal ratchet.

A Brownian particle's random motions can be rectified by a periodic potential-energy landscape that alternates between two states, even if both states are spatially symmetric. If the two states differ only by a discrete translation, the direction of the ratchet-driven current can be reversed by changing their relative durations. We experimentally demonstrate flux reversal in a symmetric two-state ratchet by tracking the motions of colloidal spheres moving through large arrays of discrete potential-energy wells created with dynamic holographic optical tweezers. The model's simplicity and high degree of symmetry suggest possible applications in molecular-scale motors.

Computer Simulation↗

PubMed2005

Colloidal electroconvection in a thin horizontal cell. I. Microscopic cooperative patterns at low voltage.

Applying an electric field to an aqueous colloidal dispersion establishes a complex interplay of forces among the highly mobile simple ions, the more highly charged but less mobile colloidal spheres, and the surrounding water. This interplay can induce a wide variety of visually striking dynamical instabilities even when the applied field is constant. This paper reports on the highly organized patterns that emerge when electrohydrodynamic forces compete with gravity in thin layers of charge-stabilized colloidal spheres subjected to low voltages between parallel-plate electrodes. Depending on the conditions, these spheres can form levitating clusters with morphologies ranging from tumbling clouds to toroidal vortex rings and to writhing labyrinths.

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PubMed2005

Observation of flux reversal in a symmetric optical thermal ratchet.

We demonstrate that a cycle of three holographic optical trapping patterns can implement a thermal ratchet for diffusing colloidal spheres and that the ratchet-driven transport displays flux reversal as a function of the cycle frequency and the intertrap separation. Unlike previously described ratchet models, the approach we describe involves three equivalent states, each of which is locally and globally spatially symmetric, with spatiotemporal symmetry being broken by the sequence of states.

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PubMed2005

Structure and scaling of helical modes of light.

Modes of light that contain topological defects such as screw dislocations can be focused into optical traps with interesting and useful properties. The way in which the intensity distribution within helical modes of light varies with topological charge is discussed, and new scaling predictions for their radial profiles that are consistent with experimental observations are introduced.

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PubMed2005

Configurational temperatures and interactions in charge-stabilized colloid.

A system's temperature can be expressed in terms of its constituents' instantaneous positions rather than their momenta. Such configurational temperature definitions offer substantial benefits for experimental studies of soft condensed matter systems, most notably their applicability to overdamped systems whose instantaneous momenta may not be accessible. We demonstrate that the configurational temperature formalism can be derived from the classical hypervirial theorem, and introduce a hierarchy of hyperconfigurational temperature definitions, which are particularly well suited for experimental studies. We then use these analytical tools to probe the electrostatic interactions in monolayers of charge-stabilized colloidal spheres confined by parallel glass surfaces. The configurational and hyperconfigurational temperatures, together with a thermodynamic sum rule, provide previously lacking self-consistency tests for interaction measurements based on digital video microscopy, and thereby cast light on controversial reports of confinement-induced like-charge attractions. We further introduce a method to determine unknown parameters in a model potential by using consistency of the configurational and hyperconfigurational temperatures as a set of constraints. This approach, in principle, also should provide the basis for a model-free estimation of the pair potential.

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PubMed2005

Management of bronchopulmonary dysplasia in infants: guidelines for corticosteroid use.

Bronchopulmonary dysplasia (BPD) is a common cause of morbidity and mortality in preterm neonates and at present its management is unclear. Over the past three decades there has been a growing use of corticosteroids in the postnatal period; first for the treatment and then, more recently, for the prevention of BPD. The first published use of corticosteroids to treat neonatal lung disease was in 1956; however, it was only in the 1980s and 1990s that their use in neonates became commonplace. Concerns about their long-term neurodevelopmental consequences arose in the late 1990s when follow-up of randomised controlled trials indicated an increased risk of cerebral palsy after postnatal dexamethasone exposure. Dexamethasone has been the most frequently used corticosteroid in neonatal units, although others, including hydrocortisone, prednisolone and methylprednisolone, have been studied, as have inhaled corticosteroids. Systematic reviews indicate that systemic corticosteroids improve respiratory function in the short term and expedite extubation in preterm neonates. However, there is a high risk of hypertension, hyperglycaemia and gastrointestinal complications in corticosteroid-treated neonates and, if administered in the first 4 days of life, an association with long-term neurodevelopmental delay. There should be emphasis on prevention of BPD by reducing the risk factors associated with its development. There is no role for use of corticosteroids in the first 4 days of life as the high risk of long-term adverse effects outweighs any likely short-term benefits. Corticosteroid use should be limited to exceptional clinical circumstances, such as a ventilator-dependent infant after the second week of life who cannot be weaned from ventilation and whose condition is worsening. If used, they should be prescribed at the lowest effective dose for the shortest possible time. Further randomised trials of low-dose corticosteroids given after the first week of life are warranted and should assess both short- and long-term outcomes.

Adrenal Cortex Hormones↗

PubMed2004

Transport and fractionation in periodic potential-energy landscapes.

Objects driven through periodically modulated potential-energy landscapes in two dimensions can become locked in to symmetry-selected directions that are independent of the driving force's orientation. We investigate this problem in the overdamped limit, and demonstrate that the crossover from free-flowing to locked-in transport can depend exponentially on an object's size, with this exceptional selectivity emerging from the landscape's periodicity.

Journal Article↗

PubMed2004

Configurational temperature of charge-stabilized colloidal monolayers.

Recent theoretical advances show that the temperature of a system in equilibrium can be measured from static snapshots of its constituents' instantaneous configurations, without regard to their dynamics. We report the first measurements of the configurational temperature in an experimental system. In particular, we introduce a hierarchy of hyperconfigurational temperature definitions, which we use to analyze monolayers of charge-stabilized colloidal spheres. Equality of the hyperconfigurational and bulk thermodynamic temperatures provides previously lacking thermodynamic self-consistency checks for the measured colloidal pair potentials, and thereby casts new light on anomalous like-charge colloidal attractions induced by geometric confinement.

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PubMed2004

Statistically locked-in transport through periodic potential landscapes.

Classical particles driven through periodically modulated potential energy landscapes are predicted to follow a devil's staircase hierarchy of commensurate trajectories depending on the orientation of the driving force. Recent experiments on colloidal spheres flowing through arrays of optical traps do indeed reveal such a hierarchy, but not with the predicted structure. The microscopic trajectories, moreover, appear to be random, with commensurability emerging only in a statistical sense. We introduce an idealized model for periodically modulated transport in the presence of randomness that captures both the structure and statistics of such statistically locked-in states.

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