Both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are associated with poor radiologic outcomes in patients with rheumatoid arthritis (RA). In general, RA patients ...positive for RF or ACPA (SPRA) are considered to manifest an aggressive disease course compared with seronegative RA patients (SNRA). However, the relationship between seropositivity and measures of disease severity other than radiologic outcome is disputed. In this study, we sought to compare the clinical presentations and treatment outcomes of SNRA and SPRA patients. A total of 241 patients diagnosed with DMARD-naïve RA under either 1987 American College of Rheumatology (ACR) criteria or 2010 ACR/European League Against Rheumatism (EULAR) criteria were identified (40 with SNRA and 201 with SPRA). We investigated the disease activity measures including ESR, CRP, patient VAS, 28 tender/swollen joint count (28 TJC, 28 SJC) and DAS28 as well as radiologic outcomes at baseline, 1 and 2 years after conventional treatment with DMARD. Age, sex and disease duration were similar between SNRA and SPRA. However, the baseline 28 TJC (4.7±2.9 vs. 3.3±2.7, p = 0.004), 28 SJC (4.3±3.0 vs. 2.9±2.3, p = 0.001) and DAS28 (5.1±1.0 vs. 4.7±1.0, p = 0.043) components were significantly higher in SNRA than in SPRA. Over 2 years of similar treatment with DMARDs, all disease activity measures significantly improved in both groups. Comparison among populations matched for baseline disease activity showed that ΔDAS28 at 1 year was greater in SNRA than in SPRA (-2.84±1.32 vs. -3.70±1.29, p = 0.037) in high disease activity population (DAS28-ESR>5.1). Radiologic outcomes at baseline and at 1- or 2-year follow-up were similar between the 2 groups. In conclusion, SNRA patients manifested more active disease at baseline, but showed a better response to treatment compared with SPRA. SNRA does not appear to be a benign subtype of RA.
Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an ...unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsis-specific treatment.
Light-field imaging and holographic imaging are currently the two mostly investigated 3-D imaging technologies because of their potentials to create the viewing environment conforming to a natural ...viewing condition. The basic optical geometries for image display in these imaging are not different from that of integral photography. The images in the two type of imaging are a set of different view images. These images are arranged as a 2-D point image array, and each point image is expanded with a certain angle to form a viewing zone. The differences between the two types of imaging are the number of point images in the array and the physical entities forming the images. Holographic imaging has many more point images than light-field imaging, and each image in the array consists of coherent right rays from different positions of an object. In light-field imaging, an array of pixels represents a direction view of the object. Despite these differences, they share the same goal of providing a continuous parallax to viewers and require display panels of almost the same characteristics. It is expected that in the future these two imaging techniques will be integrated into the same flat panel along with the plane image.
A crumpled configuration of graphene is desirable for preventing irreversible stacking between individual nanosheets, which can be a major hurdle toward its widespread application. Herein a ...sea‐urchin‐shaped template approach is introduced for fabricating highly crumpled graphene balls in bulk quantities with a simple process. Simultaneous chemical etching and reduction process of graphene oxide (GO)‐encapsulated iron oxide particles results in dissolution of the core template with spiky morphology and conversion of the outer GO layers into reduced GO layers with increased hydrophobicity which remain in contact with the spiky surface of the template. After completely etching, the outer graphene layers are fully compressed into the crumpled form along with decrease in total volume by etching. The crumpled balls exhibit significantly larger surface area and good water‐dispersion stability than those of stacked reduced GO or other crumple approaches, even though they also show comparable electrical conductivity. Furthermore, they are easily assembled into 3D macroporous networks without any binders through typical processes such as solvent casting or compression molding. The graphene networks with less pore volume still have the crumpled morphology without sacrificing the properties regardless of the assembly processes, producing a promising active electrode material with high gravimetric and volumetric energy density for capacitive energy storage.
Highly crumpled graphene balls with a sea‐urchin‐shaped template strategy are facilely fabricated in bulk quantities with high yield through simultaneous etching–reduction of graphene oxide‐encapsulated iron oxide. The crumpled balls, which exhibit significantly larger surface area and higher water‐dispersion stability than those of stacked graphene and other crumpling approaches, and their 3D macroporous networks present superior gravimetric and volumetric capacitance of electrochemical energy‐storage electrodes.
The well-known conventional Kalman filter requires an accurate system model and exact stochastic information. But in a number of situations, the system model has an unknown bias, which may degrade ...the performance of the Kalman filter or may cause the filter to diverge. The effect of the unknown bias may be more pronounced on the extended Kalman filter (EKF), which is a nonlinear filter. The two-stage extended Kalman filter (TEKF) with respect to this problem has been receiving considerable attention for a long time. Recently, the optimal two-stage Kalman filter (TKF) for linear stochastic systems with a constant bias or a random bias has been proposed by several researchers. A TEKF can also be similarly derived as the optimal TKF. In the case of a random bias, the TEKF assumes that the information of a random bias is known. But the information of a random bias is unknown or partially known in general. To solve this problem, this paper proposes an adaptive two-stage extended Kalman filter (ATEKF) using an adaptive fading EKF. To verify the performance of the proposed ATEKF, the ATEKF is applied to the INS-GPS (inertial navigation system-Global Positioning System) loosely coupled system with an unknown fault bias. The proposed ATEKF tracked/estimated the unknown bias effectively although the information about the random bias was unknown.
Atopic dermatitis (AD) shows very high prevalence in Asia, with a large unmet need for effective therapeutics. Direct comparisons between European American (EA) and Asian patients with AD are ...unavailable, but earlier blood studies detected increased IL-17+–producing cell counts in Asian patients with AD.
We sought to characterize the Asian AD skin phenotype and compare it with the EA AD skin phenotype.
We performed genomic profiling (real-time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all EAs), and 27 healthy subjects (12 EAs and 15 Asians).
Although disease severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P = .77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were characteristics of lesional epidermis from Asian patients with AD (P < .05). Most (24/27) Asian patients had high IgE levels. A principal component analysis using real-time PCR data clustered the Asian AD phenotype between the EA AD and psoriasis phenotypes. TH2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A, IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene induction typified AD skin in Asian patients.
The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component. The relative pathogenic contributions of the TH17 and TH2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics.
The development of organic‐based optoelectronic technologies for the indoor Internet of Things market, which relies on ambient energy sources, has increased, with organic photovoltaics (OPVs) and ...photodetectors (OPDs) considered promising candidates for sustainable indoor electronic devices. However, the manufacturing processes of standalone OPVs and OPDs can be complex and costly, resulting in high production costs and limited scalability, thus limiting their use in a wide range of indoor applications. This study uses a multi‐component photoactive structure to develop a self‐powering dual‐functional sensory device with effective energy harvesting and sensing capabilities. The optimized device demonstrates improved free‐charge generation yield by quantifying charge carrier dynamics, with a high output power density of over 81 and 76 µW cm−2 for rigid and flexible OPVs under indoor conditions (LED 1000 lx (5200 K)). Furthermore, a single‐pixel image sensor is demonstrated as a feasible prototype for practical indoor operating in commercial settings by leveraging the excellent OPD performance with a linear dynamic range of over 130 dB in photovoltaic mode (no external bias). This apparatus with high‐performance OPV‐OPD characteristics provides a roadmap for further exploration of the potential, which can lead to synergistic effects for practical multifunctional applications in the real world by their mutual relevance.
The dual‐functional sensory device exhibits efficient molecular packing and excellent free‐charge generation yield by quantifying charge‐carrier dynamics, resulting in a high output power density of over 94 µW cm−2 for OPVs, under dim indoor illumination (LED 1000 lx). Moreover, it demonstrates the feasibility of the proposed device by developing a single‐pixel image sensor for practical indoor operation in commercial settings.
We demonstrate the quantitative pressure measurement of gas molecules in the mid-infrared using chip-based supercontinuum and cepstrum analysis without additional measurements for baseline ...normalization. A supercontinuum generated in an on-chip waveguide made of chalcogenide glass having high nonlinearity passes through CO gas and provides a transmission spectrum. The gas absorption information is deconvoluted from the original supercontinuum spectral information containing temporal fluctuation by cepstrum analysis and extracted simply by applying a bandpass filter in the temporal domain. The gas pressure estimated from the extracted absorption information is consistent with the value measured by a pressure gauge within a difference of 1.25%, despite spectral fluctuations in the supercontinuum baseline comparable to the spectral depth of the gas absorption lines.
Protein kinase C‐δ (PKCδ) is a diacylglycerol‐dependent, calcium‐independent novel PKC isoform that is engaged in various cell signaling pathways, such as cell proliferation, apoptosis, inflammation, ...and oxidative stress. In this study, we searched for proteins that bind PKCδ using a yeast two‐hybrid assay and identified murine arrest‐defective 1 (mARD1) as a binding partner. The interaction between PKCδ and mARD1 was confirmed by glutathione S‐transferase pull‐down and co‐immunoprecipitation assays. Furthermore, recombinant PKCδ phosphorylated full‐length mARD1 protein. The NetPhos online prediction tool suggested PKCδ phosphorylates Ser80, Ser108, and Ser114 residues of mARD1 with the highest probability. Based on these results, we synthesized peptides containing these sites and examined their phosphorylations using recombinant PKCδ. Autoradiography confirmed these sites were efficiently phosphorylated. Consequent mass spectrometry and peptide sequencing in combination with MALDI‐TOF MS/MS confirmed that Ser80 and Ser108 were major phosphorylation sites. The alanine mutations of Ser80 and Ser108 abolished the phosphorylation of mARD1 by PKCδ in 293T cells supporting these observations. In addition, kinase assays using various PKC isotypes showed that Ser80 of ARD1 was phosphorylated by PKCβI and PKCζ isotypes with the highest selectivity, while Ser108 and/or Ser114 were phosphorylated by PKCγ with activities comparable to that of the PKCδ isoform. Overall, these results suggest the possibility that PKCδ transduces signals by regulating phosphorylation of ARD1.
A yeast two‐hybrid assay identified murine arrest‐defective 1 (mARD1) as a binding partner of protein kinase c‐delta. Ser80 and Ser108 were found as phosphorylation sites. Our study suggests the possibility that PKCδ transduces signals by regulating the phosphorylation of ARD1.
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