943 research outputs found
PNP13: CAREGIVER HEALTH BENEFITS AND ASSOCIATED REDUCTIONS IN HEALTHCARE COSTS AS A CONSEQUENCE OF TREATING PATIENTS WITH DONEPEZIL
Asymmetric function theory
The classical theory of symmetric functions has a central position in
algebraic combinatorics, bridging aspects of representation theory,
combinatorics, and enumerative geometry. More recently, this theory has been
fruitfully extended to the larger ring of quasisymmetric functions, with
corresponding applications. Here, we survey recent work extending this theory
further to general asymmetric polynomials.Comment: 36 pages, 8 figures, 1 table. Written for the proceedings of the
Schubert calculus conference in Guangzhou, Nov. 201
Multifunctional nanoparticles for drug/gene delivery in nanomedicine
Multifunctional nanoparticles hold great promise for drug/gene delivery. Multilayered nanoparticles can act as nanomedical systems with on-board "molecular programming" to accomplish complex multi-step tasks. For example, the targeting process has only begun when the nanosystem has found the correct diseased cell of interest. Then it must pass the cell membrane and avoid enzymatic destruction within the endosomes of the cell. Since the nanosystem is only about one millionth the volume of a human cell, for it to have therapeutic efficacy with its contained package, it must deliver that drug or gene to the appropriate site within the living cell. The successive delayering of these nanosystems in a controlled fashion allows the system to accomplish operations that would be difficult or impossible to do with even complex single molecules. In addition, portions of the nanosystem may be protected from premature degradation or mistargeting to non-diseased cells. All of these problems remain major obstacles to successful drug delivery with a minimum of deleterious side effects to the patient. This paper describes some of the many components involved in the design of a general platform technology for nanomedical systems. The feasibility of most of these components has been demonstrated by our group and others. But the integration of these interacting sub-components remains a challenge. We highlight four components of this process as examples. Each subcomponent has its own sublevels of complexity. But good nanomedical systems have to be designed/engineered as a full nanomedical system, recognizing the need for the other components
Signatures of Z Vestigial Potts-nematic order in van der Waals antiferromagnets
Layered van der Waals magnets have attracted much recent attention as a
promising and versatile platform for exploring intrinsic two-dimensional
magnetism. Within this broader class, the transition metal phosphorous
trichalcogenides P stand out as particularly interesting, as they
provide a realization of honeycomb lattice magnetism and are known to display a
variety of magnetic ordering phenomena as well as superconductivity under
pressure. One example, found in a number of different materials, is
commensurate single- zigzag antiferromagnetic order, which spontaneously
breaks the spatial threefold rotation symmetry of the honeycomb
lattice. The breaking of multiple distinct symmetries in the magnetic phase
suggests the possibility of a sequence of distinct transitions as a function of
temperature, and a resulting intermediate -nematic phase which
exists as a paramagnetic vestige of zigzag magnetic order -- a scenario known
as vestigial ordering. Here, we report the observation of key signatures of
vestigial Potts-nematic order in rhombohedral FePSe. By performing linear
dichroism imaging measurements -- an ideal probe of rotational symmetry
breaking -- we find that the symmetry is already broken above the N\'eel
temperature. We show that these observations are explained by a general
Ginzburg-Landau model of vestigial nematic order driven by magnetic
fluctuations and coupled to residual strain. An analysis of the domain
structure as temperature is lowered and a comparison with zigzag-ordered
monoclinic FePS reveals a broader applicability of the Ginzburg-Landau
model in the presence of external strain, and firmly establishes the P
magnets as a new experimental venue for studying the interplay between
Potts-nematicity, magnetism and superconductivity.Comment: 6 pages, 4 figures + supplementary materia
Oncogenic Ras Disrupts Epithelial Integrity by Activating the Transmembrane Serine Protease Hepsin
Ras proteins play a causal role in human cancer by activating multiple pathways that promote cancer growth and invasion. However, little is known about how Ras induces the first diagnostic features of invasion in solid tumors, including loss of epithelial integrity and breaching of the basement membrane (BM). In this study, we found that oncogenic Ras strongly promotes the activation of hepsin, a member of the hepsin/TMPRSS type II transmembrane serine protease family. Mechanistically, the Ras-dependent hepsin activation was mediated via Raf-MEK-ERK signaling, which controlled hepsin protein stability through the heat shock transcription factor-1 stress pathway. In Ras-transformed three-dimensional mammary epithelial culture, ablation of hepsin restored desmosomal cell-cell junctions, hemidesmosomes, and BM integrity and epithelial cohesion. In tumor xenografts harboring mutant KRas, silencing of hepsin increased local invasion concomitantly with accumulation of collagen IV. These findings suggest that hepsin is a critical protease for Ras-dependent tumorigenesis, executing cell-cell and cell-matrix pathologies important for early tumor dissemination. Significance: These findings identify the cell-surface serine protease hepsin as a potential therapeutic target for its role in oncogenic Ras-mediated deregulation of epithelial cell-cell and cell-matrix interactions and cohesion of epithelial structure.Peer reviewe
Irradiation-induced Ag nanocluster nucleation in silicate glasses: analogy with photography
The synthesis of Ag nanoclusters in sodalime silicate glasses and silica was
studied by optical absorption (OA) and electron spin resonance (ESR)
experiments under both low (gamma-ray) and high (MeV ion) deposited energy
density irradiation conditions. Both types of irradiation create electrons and
holes whose density and thermal evolution - notably via their interaction with
defects - are shown to determine the clustering and growth rates of Ag
nanocrystals. We thus establish the influence of redox interactions of defects
and silver (poly)ions. The mechanisms are similar to the latent image formation
in photography: irradiation-induced photoelectrons are trapped within the glass
matrix, notably on dissolved noble metal ions and defects, which are thus
neutralized (reverse oxidation reactions are also shown to exist). Annealing
promotes metal atom diffusion, which in turn leads to cluster nuclei formation.
The cluster density depends not only on the irradiation fluence, but also - and
primarily - on the density of deposited energy and the redox properties of the
glass. Ion irradiation (i.e., large deposited energy density) is far more
effective in cluster formation, despite its lower neutralization efficiency
(from Ag+ to Ag0) as compared to gamma photon irradiation.Comment: 48 pages, 18 figures, revised version publ. in Phys. Rev. B, pdf fil
All-optical ion generation for ion trap loading
We have investigated the all-optical generation of ions by photo-ionisation
of atoms generated by pulsed laser ablation. A direct comparison between a
resistively heated oven source and pulsed laser ablation is reported. Pulsed
laser ablation with 10 ns Nd:YAG laser pulses is shown to produce large calcium
flux, corresponding to atomic beams produced with oven temperatures greater
than 650 K. For an equivalent atomic flux, pulsed laser ablation is shown to
produce a thermal load more than one order of magnitude smaller than the oven
source. The atomic beam distributions obey Maxwell-Boltzmann statistics with
most probable speeds corresponding to temperatures greater than 2200 K. Below a
threshold pulse fluence between 280 mJ/cm^2 and 330 mJ/cm^2, the atomic beam is
composed exclusively of ground state atoms. For higher fluences ions and
excited atoms are generated.Comment: 7 pages, 9 figure
DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics
The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics
1060 nm VCSELs for long-reach optical interconnects
Reach extension of high capacity optical interconnects based on vertical-cavity surface-emitting lasers (VCSELs) and multimode fibers (MMFs), as needed for large-scale data centers, would benefit from high-speed GaAs-based VCSELs at 1060 nm. At this wavelength, the chromatic dispersion and attenuation of the optical fiber are much reduced in comparison with 850 nm. We present single and multimode 1060 nm VCSELs based on designs derived partly from our high-speed 850 nm VCSEL designs. The single-mode VCSEL, with a modulation bandwidth exceeding 22 GHz, supports back-to-back data rates up to 50 Gbps at 25 \ub0C and 40 Gbps at 85 \ub0C under binary NRZ (OOK) modulation. Using mode-selective launch, we demonstrate error-free 25 Gbps transmission over 1000 m of 1060 nm optimized MMF. Higher data rates and/or longer distances will be possible with equalization, forward-error-correction, and/or multilevel modulation
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