8,003 research outputs found
Zebrafish Model of MLL-Rearranged Acute Myeloid Leukemia
Background: Acute myeloid leukemia (AML) is the second most common type of leukemia. Standard treatment includes chemotherapy as well as stem cell transplantation, but for aging patients and those with impaired immune function these rigorous therapies are not always possible. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) exhibit far worse prognoses than patients without. Given these circumstances new therapies must be developed.
Methods: Danio rerio (zebrafish) has emerged as a powerful model organism for investigating human blood malignancies due to the conservation of hematopoiesis between humans and zebrafish. We developed a transient transgenic model exhibiting AML characteristics by microinjecting single-cell zebrafish embryos with a tissue specific MLL-ENL expression construct.
Results: We found that the expression of MLL-ENL induced a clustered expansion of MLL+ and pu.1+ myeloid cells on the yolk sac at 48 and 72 hours post fertilization (hpf). To characterize our transient AML model, we treated MLL-ENL expressing embryos with either one of or a combination of two drugs that are currently being used in human AML drug trials, Venetoclax and Flavopiridol. We found that treatment with either drug reduced the myeloid expansion induced by the expression of MLL-ENL, and that co-treatment reduced the observed myeloid expansion even further.
Conclusions: Although further analysis is required, these data suggest that we successfully developed a transient transgenic AML model in zebrafish. Furthermore, these data suggest that Venetoclax and Flavopiridol co-treatment could yield better outcomes for AML patients than treatment with either drug individually.https://scholarscompass.vcu.edu/gradposters/1112/thumbnail.jp
Elicitation of protective immune responses using a bivalent H5N1 VLP vaccine
<p>Abstract</p> <p>Background</p> <p>Currently licensed human vaccines are subtype-specific and do not protect against pandemic H5N1 viruses. Previously, our group has reported on the construction of an influenza virus-like particle (VLP) as a new generation candidate vaccine. A mixture of influenza H5N1 VLPs representing clade 1 and 2 viruses were examined for the ability to elicit protective immunity against isolates from various clades and subclades of H5N1.</p> <p>Results</p> <p>Mice were vaccinated intramuscularly with each VLP individually, the mixture of VLPs, a mixture of purified recombinant hemagglutinin (rHA), or mock vaccinated. Elicited antibodies were assayed for the hemagglutination-inhibition (HAI) activity against clades 1 and clade 2 isolates. Mice vaccinated with each VLP individually or in a mixture had robust HAI responses against homologous viruses and HAI responses against the clade 2.3 virus, Anh/05. However, these vaccines did not induce an HAI response against the clade 2.2 virus, WS/05. Interestingly, clade 2 VLP vaccinated mice were protected against both clade 1 and 2 H5/PR8 viruses, but clade 1 VLP vaccinated mice were only protected against the clade 1 virus. Mice vaccinated with a mixture of VLPs were protected against both clade 1 and 2 viruses. In contrast, mice vaccinated with a mixture of rHA survived challenge, but lost ~15% of original weight by days 5–7 post-challenge.</p> <p>Conclusion</p> <p>These results demonstrate that a multivalent influenza VLP vaccine representing different genetic clades is a promising strategy to elicit protective immunity against isolates from emerging clades and subclades of H5N1.</p
Mental Illness and Mental Health: The Two Continua Model Across the Lifespan
Mental health has long been defined as the absence of psychopathologies, such as depression and anxiety. The absence of mental illness, however, is a minimal outcome from a psychological perspective on lifespan development. This article therefore focuses on mental illness as well as on three core components of positive mental health: feelings of happiness and satisfaction with life (emotional well-being), positive individual functioning in terms of self-realization (psychological well-being), and positive societal functioning in terms of being of social value (social well-being). The two continua model holds that mental illness and mental health are related but distinct dimensions. This model was studied on the basis of a cross-sectional representative internet survey of Dutch adults (N = 1,340; 18–87 years). Mental illness was measured with the Brief Symptom Inventory and mental health with the Mental Health Continuum Short Form. It was found that older adults, except for the oldest-old, scored lower on psychopathological symptoms and were less likely to be mentally ill than younger adults. Although there were fewer age differences for mental health, older adults experienced more emotional, similar social and slightly lower psychological well-being. In sum, today’s older adults have fewer mental illness problems, but they are not in a better positive mental health than today’s younger adults. These findings support the validity of the two continua model in adult development
Intrinsic Optical and Electronic Properties from Quantitative Analysis of Plasmonic Semiconductor Nanocrystal Ensemble Optical Extinction
The optical extinction spectra arising from localized surface plasmon
resonance in doped semiconductor nanocrystals (NCs) have intensities and
lineshapes determined by free charge carrier concentrations and the various
mechanisms for damping the oscillation of those free carriers. However, these
intrinsic properties are convoluted by heterogeneous broadening when measuring
spectra of ensembles. We reveal that the traditional Drude approximation is not
equipped to fit spectra from a heterogeneous ensemble of doped semiconductor
NCs and produces fit results that violate Mie scattering theory. The
heterogeneous ensemble Drude approximation (HEDA) model rectifies this issue by
accounting for ensemble heterogeneity and near-surface depletion. The HEDA
model is applied to tin-doped indium oxide NCs for a range of sizes and doping
levels but we expect it can be employed for any isotropic plasmonic particles
in the quasistatic regime. It captures individual NC optical properties and
their contributions to the ensemble spectra thereby enabling the analysis of
intrinsic NC properties from an ensemble measurement. Quality factors for the
average NC in each ensemble are quantified and found to be notably higher than
those of the ensemble. Carrier mobility and conductivity derived from HEDA fits
matches that measured in the bulk thin film literature
Single-Shot Electron Diffraction using a Cold Atom Electron Source
Cold atom electron sources are a promising alternative to traditional
photocathode sources for use in ultrafast electron diffraction due to greatly
reduced electron temperature at creation, and the potential for a corresponding
increase in brightness. Here we demonstrate single-shot, nanosecond electron
diffraction from monocrystalline gold using cold electron bunches generated in
a cold atom electron source. The diffraction patterns have sufficient signal to
allow registration of multiple single-shot images, generating an averaged image
with significantly higher signal-to-noise ratio than obtained with unregistered
averaging. Reflection high-energy electron diffraction (RHEED) was also
demonstrated, showing that cold atom electron sources may be useful in
resolving nanosecond dynamics of nanometre scale near-surface structures.Comment: This is an author-created, un-copyedited version of an article
published in Journal of Physics B: Atomic, Molecular and Optical Physics. IOP
Publishing Ltd is not responsible for any errors or omissions in this version
of the manuscript or any version derived from it. The Version of Record is
available online at http://dx.doi.org/10.1088/0953-4075/48/21/21400
Geometrical families of mechanically stable granular packings
We enumerate and classify nearly all of the possible mechanically stable (MS)
packings of bidipserse mixtures of frictionless disks in small sheared systems.
We find that MS packings form continuous geometrical families, where each
family is defined by its particular network of particle contacts. We also
monitor the dynamics of MS packings along geometrical families by applying
quasistatic simple shear strain at zero pressure. For small numbers of
particles (N < 16), we find that the dynamics is deterministic and highly
contracting. That is, if the system is initialized in a MS packing at a given
shear strain, it will quickly lock into a periodic orbit at subsequent shear
strain, and therefore sample only a very small fraction of the possible MS
packings in steady state. In studies with N>16, we observe an increase in the
period and random splittings of the trajectories caused by bifurcations in
configuration space. We argue that the ratio of the splitting and contraction
rates in large systems will determine the distribution of MS-packing
geometrical families visited in steady-state. This work is part of our
long-term research program to develop a master-equation formalism to describe
macroscopic slowly driven granular systems in terms of collections of small
subsystems.Comment: 18 pages, 23 figures, 5 table
Characterization and cloning of fasciclin I and fasciclin II glycoproteins in the grasshopper
Monoclonal antibodies were previously used to identify two glycoproteins, called fasciclin I and II (70 and 95 kDa, respectively), which are expressed on different subsets of axon fascicles in the grasshopper (Schistocerca americana) embryo. Here the monoclonal antibodies were used to purify these two membrane-associated glycoproteins for further characterization. Fasciclin II appears to be an integral membrane protein, where fasciclin I is an extrinsic membrane protein. The amino acid sequences of the amino terminus and fragments of both proteins were determined. Using synthetic oligonucleotide probes and antibody screening, we isolated genomic and cDNA clones. Partial DNA sequences of these clones indicate that they encode fasciclins I and II
Measurements of the Yield Stress in Frictionless Granular Systems
We perform extensive molecular dynamics simulations of 2D frictionless
granular materials to determine whether these systems can be characterized by a
single static yield shear stress. We consider boundary-driven planar shear at
constant volume and either constant shear force or constant shear velocity.
Under steady flow conditions, these two ensembles give similar results for the
average shear stress versus shear velocity. However, near jamming it is
possible that the shear stress required to initiate shear flow can differ
substantially from the shear stress required to maintain flow. We perform
several measurements of the shear stress near the initiation and cessation of
flow. At fixed shear velocity, we measure the average shear stress
in the limit of zero shear velocity. At fixed shear force, we
measure the minimum shear stress required to maintain steady flow
at long times. We find that in finite-size systems ,
which implies that there is a jump discontinuity in the shear velocity from
zero to a finite value when these systems begin flowing at constant shear
force. However, our simulations show that the difference , and thus the discontinuity in the shear velocity, tend to zero in
the infinite system size limit. Thus, our results indicate that in the large
system limit, frictionless granular systems are characterized by a single
static yield shear stress. We also monitor the short-time response of these
systems to applied shear and show that the packing fraction of the system and
shape of the velocity profile can strongly influence whether or not the shear
stress at short times overshoots the long-time average value.Comment: 7 pages and 6 figure
The calcium current in inner segments of rods from the salamander (Ambystoma tigrinum) retina.
Solitary rod inner segments were isolated from salamander retinae. Their Ca current was studied with the 'whole-cell, gigaseal' technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). The soluble constituents of the cytoplasm exchanged with the solution in the pipette. The external solution could be changed during continuous perfusion. Membrane voltage was controlled with a voltage clamp. After permeant ions other than Ca were replaced with impermeant ions (i.e. tetraethylammonium as a cation, and aspartate or methanesulphonate as an anion), an inward current remained. It activated at approximately -40 mV, reached a maximum at approximately 0 mV, and decreased as the membrane was further depolarized. The size of the current increased when Ba was substituted for external Ca. The current was blocked when Ca was replaced with Co. The voltage at which the current was half-maximum shifted from approximately -22 to -31 mV during the initial 3 min of an experiment. The maximum amplitude of the current continuously declined during the entire course of an experiment. The time course for activation of the Ca current following a step of depolarization could be described by the sum of two exponentials. The time constant of the slower exponential was voltage dependent. Deactivation following repolarization could also be described by the sum of two exponentials. Both time constants for deactivation were independent of voltage (between -30 and 0 mV) and faster than the slower time constant for activation. When the internal Ca concentration was buffered by 10 mM-EGTA, the Ca current did not inactivate during several seconds of maintained depolarization. When the concentration of EGTA was reduced to 0.1 mM, the Ca current declined and the membrane conductance decreased during several seconds of maintained depolarization. This inactivation was incomplete and only occurred after a substantial quantity of Ca entered. Following repolarization the Ca conductance recovered from inactivation. In contrast, the continuous decline observed during the course of an experiment (item 3) was not reversible. The difference suggests that inactivation and the decline are distinct processes
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