Summary
RNA‐binding nuclear antigens are a major class of self‐antigen to which immune tolerance is lost in rheumatic diseases. Serological tolerance to one such antigen, La/Sjögren's syndrome (SS)‐B ...(La), is controlled by CD4+ T cells. This study investigated peripheral tolerance to human La (hLa) by tracking the fate of hLa‐specific CD4+ T cells expressing the transgenic (Tg) 3B5.8 T cell receptor (TCR) after adoptive transfer into lymphocyte‐replete recipient mice expressing hLa as a neo‐self‐antigen. After initial antigen‐specific cell division, hLa‐specific donor CD4+ T cells expressed forkhead box protein 3 (FoxP3). Donor cells retrieved from hLa Tg recipients displayed impaired proliferation and secreted interleukin (IL)−10 in vitro in response to antigenic stimulation. Transfer of highly purified FoxP3‐negative donor cells demonstrated that accumulation of hLa‐specific regulatory T cells (Treg) was due primarily to expansion of small numbers of donor Treg. Depletion of recipient plasmacytoid dendritic cells (pDC), but not B cells, severely hampered the accumulation of FoxP3+ donor Treg in hLa Tg recipients. Recipient pDC expressed tolerogenic markers and higher levels of co‐stimulatory and co‐inhibitory molecules than B cells. Adoptive transfer of hLa peptide‐loaded pDC into mice lacking expression of hLa recapitulated the accumulation of hLa‐specific Treg. Blockade of the type 1 interferon (IFN) receptor in hLa Tg recipients of hLa‐specific T cells impaired FoxP3+ donor T cell accumulation. Therefore, peripheral expansion of Treg specific for an RNA‐binding nuclear antigen is mediated by antigen‐presenting pDC in a type 1 IFN‐dependent manner. These results reveal a regulatory function of pDC in controlling autoreactivity to RNA‐binding nuclear antigens.
A regulatory function of plasmacytoid dendritic cells and type 1 interferon in promoting expansion of regulatory T cells specific for the La/Sjögren’s syndrome B antigen in the periphery of mice is revealed using T cell adoptive transfer. Depletion of plasmacytoid dendritic cells (120G8), which constitutively present La epitopes in association with MHC class II, as well as blockade of type 1 interferon signaling (not shown) impaired regulatory T cell expansion. Depletion of B cells had no effect (MB20).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We report the discovery of two new millisecond pulsars (PSRs J0024−7204aa and J0024−7204ab) in the globular cluster 47 Tucanae (NGC 104). Our results bring the total number of pulsars in 47 Tucanae ...to 25. These pulsars were discovered by reprocessing archival observations from the Parkes radio telescope. We reprocessed the data using a standard search procedure based on the presto software package as well as using a new method in which we incoherently added the power spectra corresponding to ∼1100 h of observations. The newly discovered PSR J0024−7204aa, has a pulse frequency of ∼541 Hz (corresponding to a ∼1.84 ms period), which is higher than any other pulsars currently known in the cluster and ranks 12th amongst all the currently known pulsars. The dispersion measure of this pulsar, 24.941(7) cm−3 pc, is the highest in the cluster. The second discovered pulsar, PSR J0024−7204ab, is an isolated pulsar with a pulse frequency of ∼270 Hz (corresponding to a period of ∼3.70 ms).
The article presents a charge-domain computing ternary neural network (TNN) classifier with a complete four-layer neural network (NN) on a chip. The proposed ternary network provides 1.5-b resolution ...(0/+1/−1) for weights and activations, leading to 3.9× fewer operations (OPs) per inference than binary neural network (BNN) for the same Modified National Institute of Standards and Technology (MNIST) accuracy. The 1.5-b multiply-and-accumulate (MAC) is implemented by <inline-formula> <tex-math notation="LaTeX">V_{\text {CM}} </tex-math></inline-formula>-based capacitor switching scheme, which inherently benefits from the reduced signal swing on the capacitive digital-to-analog converter (CDAC). Also, the <inline-formula> <tex-math notation="LaTeX">V_{\text {CM}} </tex-math></inline-formula>-based MAC introduces sparsity during training, resulting in a lower switching rate. The prototype is fabricated in a 40-nm LP CMOS process with an active area of 0.98 mm2, operates at 549 frames/s (FPS), and consumes 96 <inline-formula> <tex-math notation="LaTeX">\mu \text{W} </tex-math></inline-formula>. With all OPs on the chip, it achieves 97.1% MNIST accuracy with 0.18 <inline-formula> <tex-math notation="LaTeX">\mu \text{J} </tex-math></inline-formula> per classification, which is the smallest to our knowledge for comparable MNIST classification accuracy.
In the post Moore's era, conventional electronic digital computing platforms have encountered escalating challenges to support massively parallel and energy-hungry artificial intelligence (AI) ...workloads. Intelligent applications in data centers, edge devices, and autonomous vehicles have restricted requirements in throughput, power, and latency, which raises a high demand for a revolutionary neurocomputing solution. Optical neural network (ONN) is a promising hardware platform that could represent a paradigm shift in efficient neurocomputing with its ultra-fast speed, high parallelism, and low energy consumption. In recent years, efforts have been made to facilitate the ONN design stack and push forward the practical application of optical neural accelerators. In this tutorial, we give an overview of state-of-the-art cross-layer co-design methodologies for scalable, robust, and self-learnable ONN designs across the circuit, architecture, and algorithm levels. Besides, we analyze challenges and highlight emerging directions targeting next-generation optics for AI.
Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor that is activated by trypsin-like proteinases. PAR2 is detected in breast tumor specimens; however, it is not clear how PAR2 ...level in breast cancer cell/tissues compares with normal cell/tissues. Here, we show the elevation of PAR2 protein level in 76 of 105 breast tumor specimens but only 5 of 24 normal breast tissues. PAR2 level is also higher in breast cancer cell lines than that in normal breast cells and non-cancerous breast cell lines. To determine the role of PAR2 in breast carcinogenesis, we examined the effect of PAR2 agonists on cell proliferation and migration. Our studies show that PAR2 agonists (PAR2-activating peptide and trypsin) are neither potent growth enhancers nor chemoattractants to breast cancer cells. Instead, PAR2 agonists induce significant chemokinesis. PAR2-mediated chemokinesis is G(alphai)-dependent, and inhibiting Src kinase activity or silencing c-Src expression blocks PAR2-mediated chemokinesis. These results suggest that c-Src works downstream of G(alphai) to mediate this PAR2 agonist-induced event. To characterize c-Src effector, we reveal that PAR2 agonists activate JNKs in a Src-dependent manner and that JNK activity is essential for PAR2-mediated chemokinesis. Moreover, PAR2 agonist stimulation leads to paxillin Ser(178) phosphorylation and paxillin(S178A) mutant inhibits PAR2-mediated chemokinesis. In conclusion, our studies show that PAR2 agonists facilitate breast cancer cell chemokinesis through the G(alphai)-c-Src-JNK-paxillin signaling pathway.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Planck collaboration has measured the temperature and polarization of the cosmic microwave background well enough to determine the locations of eight peaks in the temperature (TT) power spectrum, ...five peaks in the polarization (EE) power spectrum and 12 extrema in the cross (TE) power spectrum. The relative locations of these extrema give a striking, and beautiful, demonstration of what we expect from acoustic oscillations in the plasma; e.g. that EE peaks fall half way between TT peaks. We expect this because the temperature map is predominantly sourced by temperature variations in the last scattering surface, while the polarization map is predominantly sourced by gradients in the velocity field, and the harmonic oscillations have temperature and velocity 90 deg out of phase. However, there are large differences in expectations for extrema locations from simple analytic models versus numerical calculations. Here, we quantitatively explore the origin of these differences in gravitational potential transients, neutrino free-streaming, the breakdown of tight coupling, the shape of the primordial power spectrum, details of the geometric projection from three to two dimensions, and the thickness of the last scattering surface. We also compare the peak locations determined from Planck measurements to expectations under the Λ cold dark matter model. Taking into account how the peak locations were determined, we find them to be in agreement.
Layout Decomposition for Triple Patterning Lithography Bei Yu; Kun Yuan; Duo Ding ...
IEEE transactions on computer-aided design of integrated circuits and systems,
2015-March, 2015-3-00, 20150301, Volume:
34, Issue:
3
Journal Article
Peer reviewed
Open access
As minimum feature size and pitch spacing further scale down, triple patterning lithography is a likely 193 nm extension along the paradigm of double patterning lithography for 14-nm technology node. ...Layout decomposition, which divides input layout into several masks to minimize the conflict and stitch numbers, is a crucial design step for double/triple patterning lithography. In this paper, we present a systematic study on triple patterning layout decomposition problem, which is shown to be NP-hard. Because of the NP-hardness, the runtime required to exactly solve it increases dramatically with the problem size. We first propose a set of graph division techniques to reduce the problem size. Then, we develop integer linear programming (ILP) to solve it. For large layouts, even with the graph-division techniques, ILP may still suffer from serious runtime overhead. To achieve better trade-off between runtime and performance, we present a novel semidefinite programming (SDP)-based algorithm. Followed by a mapping process, we can translate the SDP solutions into the final decomposition solutions. Experimental results show that the graph division can reduce runtime dramatically. In addition, SDP-based algorithm can achieve great speedup even compared with accelerated ILP, with very comparable results in terms of the stitch number and the conflict number.
In this paper, we survey key design for manufacturing issues for extreme scaling with emerging nanolithography technologies, including double/multiple patterning lithography, extreme ultraviolet ...lithography, and electron-beam lithography. These nanolithography and nanopatterning technologies have different manufacturing processes and their unique challenges to very large scale integration (VLSI) physical design, mask synthesis, and so on. It is essential to have close VLSI design and underlying process technology co-optimization to achieve high product quality (power/performance, etc.) and yield while making future scaling cost-effective and worthwhile. Recent results and examples will be discussed to show the enablement and effectiveness of such design and process integration, including lithography model/analysis, mask synthesis, and lithography friendly physical design.
Reversible reactions exhibit considerable potential for thermal energy storage because of their high energy density and capability for long-term storage at ambient temperature. This paper presents ...the research progress on gas–solid thermochemical heat storage reactors and their corresponding systems. The comprehensive state-of-the-art knowledge on gas–solid thermochemical reactors, namely, packed bed, continuous, and direct-type reactors, for high-temperature heat storage applications is reviewed. Up till now, the performance of packed bed reactors has been extensively investigated. However, the intrinsic drawbacks of packed bed reactors limit their applications. Continuous and direct-type reactors can efficiently store heat, but studies on these reactors are still on the stage of material characterization and prototype designing. Various numerical studies have successfully predicted the reaction trends in the three reactors to elucidate their performances and features. In these studies, porous thermochemical materials are studied on the scale of representative element volume. So far, numerical or experimental approaches have been rarely used to investigate physical and chemical processes at the particle scale. Energy and exergy analyses on conceptual thermochemical heat storage systems came into existence recently. In the future, more efficiency analyses based on practical experimental results are required.
•Packed bed, continuous, and direct-type reactors are reviewed.•An overview of available heat storage systems for different reactors is given.•Various numerical studies for different reactors are discussed.•Energy and energy efficiencies for different systems are analyzed.•Feasible reactors for various high-temperature gas–solid reactions are evaluated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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