397 research outputs found
Engineering nanomedicines using stimuli-responsive biomaterials
The ability to engineer particles has the potential to shift the paradigm in the creation of new medicines and diagnostics. Complete control over particle characteristics, such as size, shape, mechanical property, and surface chemistry, can enable rapid translation and facilitate the US Food and Drug Administration (FDA) approval of particle technologies for the treatment of cancer, infectious diseases, diabetes, and a host of other major illnesses. The incorporation of natural and artificial external stimuli to trigger the release of drugs enables exquisite control over the release profiles of drugs in a given environment. In this article, we examine several readily scalable top-down methods for the fabrication of shape-specific particles that utilize stimuli-responsive biomaterials for controlled drug delivery. Special attention is given to Particle Replication In Nonwetting Templates (PRINT®) technology and the application of novel triggered-release synthetic and natural polymers
More Effective Nanomedicines through Particle Design
Nanomedicine is an emerging field that applies concepts in nanotechnology to the development of novel diagnostics and therapeutics. Physical and chemical properties of particles, including size, shape, modulus, surface charge and surface chemistry, play important roles in the efficacy of nanomedicines. This review focuses on the effect of particle physical and chemical properties on their interactions with cells in vitro and their pharmacokinetics and biodistribution in vivo
Tunable Bifunctional Silyl Ether Cross-Linkers for the Design of Acid-Sensitive Biomaterials
Responsive polymeric biomaterials can be triggered to degrade using localized environments found in vivo. A limited number of biomaterials provide precise control over the rate of degradation, the release rate of entrapped cargo, and yield a material that is intrinsically non-toxic. Here we design non-toxic acid-sensitive biomaterials based on silyl ether chemistry. A host of silyl ether cross-linkers were synthesized and molded into relevant medical devices including Trojan horse particles, sutures, and stents. The resulting devices were engineered to degrade under acidic conditions known to exist in tumor tissue, inflammatory tissue, and within diseased cells. The implementation of silyl ether chemistry gave precise control over the rate of degradation, and depending upon the steric bulk around the silicon atom, afforded devices that could degrade over the course of hours, days, weeks, or months. These novel materials could be useful for numerous biomedical applications including drug-delivery, tissue repair, and general surgery
Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer
Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. Thi..
The 74MHz System on the Very Large Array
The Naval Research Laboratory and the National Radio Astronomy Observatory
completed implementation of a low frequency capability on the VLA at 73.8 MHz
in 1998. This frequency band offers unprecedented sensitivity (~25 mJy/beam)
and resolution (~25 arcsec) for low-frequency observations. We review the
hardware, the calibration and imaging strategies, comparing them to those at
higher frequencies, including aspects of interference excision and wide-field
imaging. Ionospheric phase fluctuations pose the major difficulty in
calibrating the array. Over restricted fields of view or at times of extremely
quiescent ionospheric ``weather'', an angle-invariant calibration strategy can
be used. In this approach a single phase correction is devised for each
antenna, typically via self-calibration. Over larger fields of view or at times
of more normal ionospheric ``weather'' when the ionospheric isoplanatic patch
size is smaller than the field of view, we adopt a field-based strategy in
which the phase correction depends upon location within the field of view. This
second calibration strategy was implemented by modeling the ionosphere above
the array using Zernike polynomials. Images of 3C sources of moderate strength
are provided as examples of routine, angle-invariant calibration and imaging.
Flux density measurements indicate that the 74 MHz flux scale at the VLA is
stable to a few percent, and tied to the Baars et al. value of Cygnus A at the
5 percent level. We also present an example of a wide-field image, devoid of
bright objects and containing hundreds of weaker sources, constructed from the
field-based calibration. We close with a summary of lessons the 74 MHz system
offers as a model for new and developing low-frequency telescopes. (Abridged)Comment: 73 pages, 46 jpeg figures, to appear in ApJ
The Pursuit of a Scalable Nanofabrication Platform for Use in Material and Life Science Applications
In this Account, we describe the use of perfluoropolyether (PFPE)-based materials that are able to accurately mold and replicate micro- and nanosized features using traditional techniques such as embossing as well as new techniques that we developed to exploit the exceptional surface characteristics of fluorinated substrates. Because of the unique partial wetting and nonwetting characteristics of PFPEs, we were able to go beyond the usual molding and imprint lithography approaches and have created a technique called PRINT (Particle [or Pattern] Replication In Nonwetting Templates)
A generalist–specialist trade-off between switchgrass cytotypes impacts climate adaptation and geographic range
Polyploidy results from whole-genome duplication and is a unique form of heritable variation with pronounced evolutionary implications. Different ploidy levels, or cytotypes, can exist within a single species, and such systems provide an opportunity to assess how ploidy variation alters phenotypic novelty, adaptability, and fitness, which can, in turn, drive the development of unique ecological niches that promote the coexistence of multiple cytotypes. Switchgrass, Panicum virgatum, is a widespread, perennial C4 grass in North America with multiple naturally occurring cytotypes, primarily tetraploids (4×) and octoploids (8×). Using a combination of genomic, quantitative genetic, landscape, and niche modeling approaches, we detect divergent levels of genetic admixture, evidence of niche differentiation, and differential environmental sensitivity between switchgrass cytotypes. Taken together, these findings support a generalist (8×)–specialist (4×) trade-off. Our results indicate that the 8× represent a unique combination of genetic variation that has allowed the expansion of switchgrass’ ecological niche and thus putatively represents a valuable breeding resource
Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft
The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system
Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC
The uncertainty on the calorimeter energy response to jets of particles is
derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the
calorimeter response to single isolated charged hadrons is measured and
compared to the Monte Carlo simulation using proton-proton collisions at
centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009
and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter
response to specific types of particles (positively and negatively charged
pions, protons, and anti-protons) is measured and compared to the Monte Carlo
predictions. Finally, the jet energy scale uncertainty is determined by
propagating the response uncertainty for single charged and neutral particles
to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3%
for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table,
submitted to European Physical Journal
Measurement of the production cross section for W-bosons in association with jets in pp collisions at s=7 TeV with the ATLAS detector
This Letter reports on a first measurement of the inclusive W + jets cross section in proton-proton collisions at a centre-of-mass energy of 7 TeV at the LHC, with the ATLAS detector. Cross sections, in both the electron and muon decay modes of the W-boson, are presented as a function of jet multiplicity and of the transverse momentum of the leading and next-to-leading jets in the event. Measurements are also presented of the ratio of cross sections sigma (W + >= n)/sigma(W + >= n - 1) for inclusive jet multiplicities n = 1-4. The results, based on an integrated luminosity of 1.3 pb(-1), have been corrected for all known detector effects and are quoted in a limited and well-defined range of jet and lepton kinematics. The measured cross sections are compared to particle-level predictions based on perturbative QCD. Next-to-leading order calculations, studied here for n <= 2, are found in good agreement with the data. Leading-order multiparton event generators, normalized to the NNLO total cross section, describe the data well for all measured jet multiplicitie
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