5,476 research outputs found
Monolithically Integrated Multilayer Silicon Nitride-on-Silicon Waveguide Platforms for 3-D Photonic Circuits and Devices
In this paper, we review and provide additional details about our progress on multilayer silicon nitride (SiN)-on-silicon (Si) integrated photonic platforms. In these platforms, one or more SiN waveguide layers are monolithically integrated onto a Si photonic layer. This paper focuses on the development of three-layer platforms for the O- and SCL-bands for very large-scale photonic integrated circuits requiring hundreds or thousands of waveguide crossings. Low-loss interlayer transitions and ultralow-loss waveguide crossings have been demonstrated, along with bilevel and trilevel grating couplers for fiber-to-chip coupling. The SiN and Si passive devices have been monolithically integrated with high-efficiency optical modulators, photodetectors, and thermal tuners in a single photonic platform
Retinal Changes in a Mutant Form of Goldfish with Megalophthalmia
The retinal changes of a mutant strain of goldfish with megalophthalmia were studied by histology, electron microscopy and biochemistry. Changes in the morphology of the pigment epithelium, decrease in number of photoreceptors, thinning out of retinal layers and the existence of spaces in the retina were all features as the eyes grew in size. Invasion of macrophages was also evident in the retina. A decrease in leucine uptake per milligram of retina was also detected as the eye grew beyond 0.8 millilitre in volume. These changes, although related to volume changes (i.e., growth) of the eyes, were found to have little relationship with increase of intraocular pressure as intraocular pressures in the growing eyes of the mutant strain did not change much. Goldfish from a control strain with similar eye volumes and sizes (ages) were used for comparison and similar changes as in the mutant were not apparent
Optical-phonon resonances with saddle-point excitons in twisted-bilayer graphene
Twisted-bilayer graphene (tBLG) exhibits van Hove singularities in the
density of states that can be tuned by changing the twisting angle . A
-defined tBLG has been produced and characterized with optical
reflectivity and resonance Raman scattering. The -engineered optical
response is shown to be consistent with persistent saddle-point excitons.
Separate resonances with Stokes and anti-Stokes Raman scattering components can
be achieved due to the sharpness of the two-dimensional saddle-point excitons,
similar to what has been previously observed for one-dimensional carbon
nanotubes. The excitation power dependence for the Stokes and anti-Stokes
emissions indicate that the two processes are correlated and that they share
the same phonon.Comment: 5 pages, 6 figure
Phosphorylation-dependent substrate selectivity of protein kinase B (AKT1)
Protein kinase B (AKT1) is a central node in a signaling pathway that regulates cell survival. The diverse pathways regulated by AKT1 are communicated in the cell via the phosphorylation of perhaps more than 100 cellular substrates. AKT1 is itself activated by phosphorylation at Thr-308 and Ser-473. Despite the fact that these phosphorylation sites are biomarkers for cancers and tumor biology, their individual roles in shaping AKT1 substrate selectivity are unknown. We recently developed a method to produce AKT1 with programmed phosphorylation at either or both of its key regulatory sites. Here, we used both defined and randomized peptide libraries to map the substrate selectivity of site-specific, singly and doubly phosphorylated AKT1 variants. To globally quantitate AKT1 substrate preferences, we synthesized three AKT1 substrate peptide libraries: one based on 84 “known” substrates and two independent and larger oriented peptide array libraries (OPALs) of ~1011 peptides each. We found that each phospho-form of AKT1 has common and distinct substrate requirements. Compared with pAKT1T308, the addition of Ser-473 phosphorylation increased AKT1 activities on some, but not all of its substrates. This is the first report that Ser-473 phosphorylation can positively or negatively regulate kinase activity in a substrate-dependent fashion. Bioinformatics analysis indicated that the OPAL-activity data effectively discriminate known AKT1 substrates from closely related kinase substrates. Our results also enabled predictions of novel AKT1 substrates that suggest new and expanded roles for AKT1 signaling in regulating cellular processes
Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.
Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma
New Low Accretion-Rate Magnetic Binary Systems and their Significance for the Evolution of Cataclysmic Variables
Discoveries of two new white dwarf plus M star binaries with striking optical
cyclotron emission features from the Sloan Digital Sky Survey (SDSS) brings to
six the total number of X-ray faint, magnetic accretion binaries that accrete
at rates < 10^{-13} Msun/yr, or <1% of the values normally encountered in
cataclysmic variables. This fact, coupled with donor stars that underfill their
Roche lobes and very cool white dwarfs, brand the binaries as post
common-envelope systems whose orbits have not yet decayed to the point of
Roche-lobe contact. They are pre-magnetic CVs, or pre-Polars. The systems
exhibit spin/orbit synchronism and apparently accrete by efficient capture of
the stellar wind from the secondary star, a process that has been dubbed a
``magnetic siphon''. Because of this, period evolution of the binaries will
occur solely by gravitational radiation, which is very slow for periods >3 hr.
Optical surveys for the cyclotron harmonics appear to be the only means of
discovery, so the space density of pre-Polars could rival that of Polars, and
the binaries provide an important channel of progenitors (in addition to the
asynchronous Intermediate Polars). Both physical and SDSS observational
selection effects are identified that may help to explain the clumping of all
six systems in a narrow range of magnetic field strength around 60 MG.Comment: 25 pages, 13 figures, Accepted to Ap
The Berkeley Sample of Stripped-Envelope Supernovae
We present the complete sample of stripped-envelope supernova (SN) spectra
observed by the Lick Observatory Supernova Search (LOSS) collaboration over the
last three decades: 888 spectra of 302 SNe, 652 published here for the first
time, with 384 spectra (of 92 SNe) having photometrically-determined phases.
After correcting for redshift and Milky Way dust reddening and reevaluating the
spectroscopic classifications for each SN, we construct mean spectra of the
three major spectral subtypes (Types IIb, Ib, and Ic) binned by phase. We
compare measures of line strengths and widths made from this sample to the
results of previous efforts, confirming that O I {\lambda}7774 absorption is
stronger and found at higher velocity in Type Ic SNe than in Types Ib or IIb
SNe in the first 30 days after peak brightness, though the widths of nebular
emission lines are consistent across subtypes. We also highlight newly
available observations for a few rare subpopulations of interest.Comment: 13 pages; 14 figures; 3 tables. Accepted for publication in MNRA
A Novel Prodrug of a nNOS Inhibitor with Improved Pharmacokinetic Potential
Under different pathological conditions, aberrant induction of neuronal nitric oxide synthase (nNOS) generates overproduction of NO that can cause irreversible cell damage. The aim of this study was to develop an amidoxime prodrug of a potent nNOS inhibitor, the benzhydryl acetamidine. We synthesized the benzhydryl acetamidoxime, which was evaluated in vitro to ascertain the potential NOS inhibitory activity, as well as conducting bioconversion into the parent acetamidine. The prodrug was also profiled for in vitro physicochemical properties, by determining the lipophilicity, passive permeation through the human gastrointestinal tract and across the blood-brain barrier by PAMPA, and chemical, enzymatic, and plasma stability. The obtained data demonstrate that the amidoxime prodrug shows an improved pharmacokinetic profile with respect to the acetamidine nNOS inhibitor, thus suggesting that it could be a promising lead compound to treat all those pathological conditions in which nNOS activity is dysregulated
SmartMal: A Service-Oriented Behavioral Malware Detection Framework for Mobile Devices
This paper presents SmartMal—a novel service-oriented behavioral malware detection framework for vehicular and mobile devices. The highlight of SmartMal is to introduce service-oriented architecture (SOA) concepts and behavior analysis into the malware detection paradigms. The proposed framework relies on client-server architecture, the client continuously extracts various features and transfers them to the server, and the server’s main task is to detect anomalies using state-of-art detection algorithms. Multiple distributed servers simultaneously analyze the feature vector using various detectors and information fusion is used to concatenate the results of detectors. We also propose a cycle-based statistical approach for mobile device anomaly detection. We accomplish this by analyzing the users’ regular usage patterns. Empirical results suggest that the proposed framework and novel anomaly detection algorithm are highly effective in detecting malware on Android devices
Coherent, mechanical control of a single electronic spin
The ability to control and manipulate spins via electrical, magnetic and
optical means has generated numerous applications in metrology and quantum
information science in recent years. A promising alternative method for spin
manipulation is the use of mechanical motion, where the oscillation of a
mechanical resonator can be magnetically coupled to a spins magnetic dipole,
which could enable scalable quantum information architectures9 and sensitive
nanoscale magnetometry. To date, however, only population control of spins has
been realized via classical motion of a mechanical resonator. Here, we
demonstrate coherent mechanical control of an individual spin under ambient
conditions using the driven motion of a mechanical resonator that is
magnetically coupled to the electronic spin of a single nitrogen-vacancy (NV)
color center in diamond. Coherent control of this hybrid mechanical/spin system
is achieved by synchronizing pulsed spin-addressing protocols (involving
optical and radiofrequency fields) to the motion of the driven oscillator,
which allows coherent mechanical manipulation of both the population and phase
of the spin via motion-induced Zeeman shifts of the NV spins energy. We
demonstrate applications of this coherent mechanical spin-control technique to
sensitive nanoscale scanning magnetometry.Comment: 6 pages, 4 figure
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