302 research outputs found
Broadband energy-efficient optical modulation by hybrid integration of silicon nanophotonics and organic electro-optic polymer
Silicon-organic hybrid integrated devices have emerging applications ranging
from high-speed optical interconnects to photonic electromagnetic-field
sensors. Silicon slot photonic crystal waveguides (PCWs) filled with
electro-optic (EO) polymers combine the slow-light effect in PCWs with the high
polarizability of EO polymers, which promises the realization of
high-performance optical modulators. In this paper, a broadband,
power-efficient, low-dispersion, and compact optical modulator based on an EO
polymer filled silicon slot PCW is presented. A small voltage-length product of
V{\pi}*L=0.282Vmm is achieved, corresponding to an unprecedented record-high
effective in-device EO coefficient (r33) of 1230pm/V. Assisted by a backside
gate voltage, the modulation response up to 50GHz is observed, with a 3-dB
bandwidth of 15GHz, and the estimated energy consumption is 94.4fJ/bit at
10Gbit/s. Furthermore, lattice-shifted PCWs are utilized to enhance the optical
bandwidth by a factor of ~10X over other modulators based on
non-band-engineered PCWs and ring-resonators.Comment: 12 pages, 4 figures, SPIE Photonics West Conference 201
Genome maps across 26 human populations reveal population-specific patterns of structural variation.
Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome
Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies
Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs
BACKGROUND:
The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear.
OBJECTIVE:
The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF.
METHODS:
We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG.
RESULTS:
We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P = .021) and 115 beats/min (95% CI 96-134 beats/min; P = .016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P = .037) and 114 beats/min (95% CI 83-146 beats/min; P = .039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG.
CONCLUSION:
VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF
Direct observation of active material concentration gradients and crystallinity breakdown in LiFePO4 electrodes during charge/discharge cycling of lithium batteries
The phase changes that occur during discharge of an electrode comprised of LiFePO4, carbon, and PTFE binder have been studied in lithium half cells by using X-ray diffraction measurements in reflection geometry. Differences in the state of charge between the front and the back of LiFePO4 electrodes have been visualized. By modifying the X-ray incident angle the depth of penetration of the X-ray beam into the electrode was altered, allowing for the examination of any concentration gradients that were present within the electrode. At high rates of discharge the electrode side facing the current collector underwent limited lithium insertion while the electrode as a whole underwent greater than 50% of discharge. This behavior is consistent with depletion at high rate of the lithium content of the electrolyte contained in the electrode pores. Increases in the diffraction peak widths indicated a breakdown of crystallinity within the active material during cycling even during the relatively short duration of these experiments, which can also be linked to cycling at high rate
Probing the Intermediate-Age Globular Clusters in NGC 5128 from Ultraviolet Observations
We explore the age distribution of the globular cluster (GC) system of the
nearby elliptical galaxy NGC 5128 using ultraviolet (UV) photometry from Galaxy
Evolution Explorer (GALEX) observations, with UV - optical colors used as the
age indicator. Most GCs in NGC 5128 follow the general trends of GCs in M31 and
Milky Way in UV - optical color-color diagram, which indicates that the
majority of GCs in NGC 5128 are old similar to the age range of old GCs in M31
and Milky Way. A large fraction of spectroscopically identified
intermediate-age GC (IAGC) candidates with ~ 3-8 Gyr are not detected in the
FUV passband. Considering the nature of intermediate-age populations being
faint in the far-UV (FUV) passband, we suggest that many of the
spectroscopically identified IAGCs may be truly intermediate in age. This is in
contrast to the case of M31 where a large fraction of spectroscopically
suggested IAGCs are detected in FUV and therefore may not be genuine IAGCs but
rather older GCs with developed blue horizontal branch stars. Our UV photometry
strengthens the results previously suggesting the presence of GC and stellar
subpopulation with intermediate age in NGC 5128. The existence of IAGCs
strongly indicates the occurrence of at least one more major star formation
episode after a starburst at high redshift.Comment: 8 pages, 3 figures, accepted for ApJ Lette
The physics of spreading processes in multilayer networks
The study of networks plays a crucial role in investigating the structure,
dynamics, and function of a wide variety of complex systems in myriad
disciplines. Despite the success of traditional network analysis, standard
networks provide a limited representation of complex systems, which often
include different types of relationships (i.e., "multiplexity") among their
constituent components and/or multiple interacting subsystems. Such structural
complexity has a significant effect on both dynamics and function. Throwing
away or aggregating available structural information can generate misleading
results and be a major obstacle towards attempts to understand complex systems.
The recent "multilayer" approach for modeling networked systems explicitly
allows the incorporation of multiplexity and other features of realistic
systems. On one hand, it allows one to couple different structural
relationships by encoding them in a convenient mathematical object. On the
other hand, it also allows one to couple different dynamical processes on top
of such interconnected structures. The resulting framework plays a crucial role
in helping achieve a thorough, accurate understanding of complex systems. The
study of multilayer networks has also revealed new physical phenomena that
remain hidden when using ordinary graphs, the traditional network
representation. Here we survey progress towards attaining a deeper
understanding of spreading processes on multilayer networks, and we highlight
some of the physical phenomena related to spreading processes that emerge from
multilayer structure.Comment: 25 pages, 4 figure
NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses
SummaryUnderstanding the negative regulators of antiviral immune responses will be critical for advancing immune-modulated antiviral strategies. NLRX1, an NLR protein that negatively regulates innate immunity, was previously identified in an unbiased siRNA screen as required for HIV infection. We find that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA. NLRX1 sequesters the DNA-sensing adaptor STING from interaction with TANK-binding kinase 1 (TBK1), which is a requisite for IFN-1 induction in response to DNA. NLRX1-deficient cells generate an amplified STING-dependent host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses. Accordingly, Nlrx1−/− mice infected with DNA viruses exhibit enhanced innate immunity and reduced viral load. Thus, NLRX1 is a negative regulator of the host innate immune response to HIV-1 and DNA viruses
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