Robust prior-based single image super resolution under multiple Gaussian degradations

Although SISR (Single Image Super Resolution) problem can be effectively solved by deep learning based methods, the training phase often considers single degradation type such as bicubic interpolation or Gaussian blur with fixed variance. These priori hypotheses often fail and lead to reconstruction error in real scenario. In this paper, we propose an end-to-end CNN model RPSRMD to handle SR problem in multiple Gaussian degradations by extracting and using as side information a shared image prior that is consistent in different Gaussian degradations. The shared image prior is generated by an AED network RPGen with a rationally designed loss function that contains two parts: consistency loss and validity loss. These losses supervise the training of AED to guarantee that the image priors of one image with different Gaussian blurs to be very similar. Afterwards we carefully designed a SR network, which is termed as PResNet (Prior based Residual Network) in this paper, to efficiently use the image priors and generate high quality and robust SR images when unknown Gaussian blur is presented. When we applied variant Gaussian blurs to the low resolution images, the experiments prove that our proposed RPSRMD, which includes RPGen and PResNet as two core components, is superior to many state-of-the-art SR methods that were designed and trained to handle multi-degradation

Design and optimization of enzymatic activity in a de novo β-barrel scaffold

While native scaffolds offer a large diversity of shapes and topologies for enzyme engineering, their often unpredictable behavior in response to sequence modification makes de novo generated scaffolds an exciting alternative. Here we explore the customization of the backbone and sequence of a de novo designed eight stranded β-barrel protein to create catalysts for a retro-aldolase model reaction. We show that active and specific catalysts can be designed in this fold and use directed evolution to further optimize activity and stereoselectivity. Our results support previous suggestions that different folds have different inherent amenability to evolution and this property could account, in part, for the distribution of natural enzymes among different folds

Disentangling superconducting and magnetic orders in NaFe_1-xNi_xAs using muon spin rotation

Muon spin rotation and relaxation studies have been performed on a "111" family of iron-based superconductors NaFe_1-xNi_xAs. Static magnetic order was characterized by obtaining the temperature and doping dependences of the local ordered magnetic moment size and the volume fraction of the magnetically ordered regions. For x = 0 and 0.4 %, a transition to a nearly-homogeneous long range magnetically ordered state is observed, while for higher x than 0.4 % magnetic order becomes more disordered and is completely suppressed for x = 1.5 %. The magnetic volume fraction continuously decreases with increasing x. The combination of magnetic and superconducting volumes implies that a spatially-overlapping coexistence of magnetism and superconductivity spans a large region of the T-x phase diagram for NaFe_1-xNi_xAs . A strong reduction of both the ordered moment size and the volume fraction is observed below the superconducting T_C for x = 0.6, 1.0, and 1.3 %, in contrast to other iron pnictides in which one of these two parameters exhibits a reduction below TC, but not both. The suppression of magnetic order is further enhanced with increased Ni doping, leading to a reentrant non-magnetic state below T_C for x = 1.3 %. The reentrant behavior indicates an interplay between antiferromagnetism and superconductivity involving competition for the same electrons. These observations are consistent with the sign-changing s-wave superconducting state, which is expected to appear on the verge of microscopic coexistence and phase separation with magnetism. We also present a universal linear relationship between the local ordered moment size and the antiferromagnetic ordering temperature TN across a variety of iron-based superconductors. We argue that this linear relationship is consistent with an itinerant-electron approach, in which Fermi surface nesting drives antiferromagnetic ordering.Comment: 20 pages, 14 figures, Correspondence should be addressed to Prof. Yasutomo Uemura: [email protected]

An Interdisciplinary Investigation of Conformational Changes in Quasi-Crystalline Protein Array R-bodies in Response to pH

Thesis (Ph.D.)--University of Washington, 2023R-bodies are ribbon-like protein polymers that undergo a dramatic conformational change from a tightly coiled form at neutral pH to an extended helical spiral at acidic pH. R-bodies were found in bacterial endosymbionts of paramecia, where their forceful extension causes vacuolar membranes to rupture contributing to a type of inter-paramecium warfare (Pond et al., 1989). Previous work has shown that R-body extension is fast, reversible, extremely robust, and tunable by directed evolution (Polka & Silver, 2016). However, it remains unknown how micron-scale changes in the conformation of an R-body ribbon arise from pH-induced changes in its nanoscale subunits. Here we use an interdisciplinary approach combining DIC microscopy, cryo-electron microscopy, atomic force microscopy, and hydrogen deuterium exchange to study individual, purified R-bodies in vitro. We show that R-body extension and contraction are highly cooperative and hysteretic processes with changes in the magnitude and direction of ribbon curvature as well as changes in ribbon thickness. Viewed en face, the R-body ribbon is a two-dimensional quasi-crystalline lattice with very small unit-cell dimensions (11.5 x 14.3 Å) that do not change with pH. Viewed edge-on, the ribbon has a laminar structure with five layers at neutral pH, two of which become indistinct at acidic pH. We show that the C-termini of the main constituent helical proteins, Reb A and Reb B, undergo large pH-dependent changes in accessibility for hydrogen-deuterium exchange, implying a transition from disordered at neutral pH to ordered helices at acidic pH. We propose this disordered-to-helical transition in the C-termini of Reb A and Reb B alters the tension within the concave side of the ribbon, driving changes in the local curvature of the ribbon to cause the extension process. Our findings provide a basis for understanding the mechanism of R-body extension, which may guide efforts to engineer R-bodies for novel drug delivery applications or to design new dynamic protein arrays

Tendon stem cells seeded on dynamic chondroitin sulfate and chitosan hydrogel scaffold with BMP2 enhance tendon-to-bone healing

Failure to adequately reconstruct the tendon-to-bone interface constitutes the primary etiology underlying rotator cuff retear after surgery. The purpose of this study is to construct a dynamic chondroitin sulfate and chitosan hydrogel scaffold (CHS) with bone morphogenetic protein 2 (BMP2), then seed tendon stem cells (TSCs) on BMP2-CHS for the rotator cuff reconstruction of tendon-to-bone interface. In this dynamic hydrogel system, the scaffold could not only have good biocompatibility and degradability but also significantly promote the proliferation and differentiation of TSCs. The ability of BMP2-CHS combined with TSCs to promote regeneration of tendon-to-bone interface was further verified in the rabbit rotator cuff tear model. The results showed that BMP2-CHS combined with TSCs could induce considerable collagen, fibrocartilage, and bone arrangement and growth at the tendon-to-bone interface and promote the biomechanical properties. Overall, TSCs seeded on CHS with BMP2 can enhance tendon-to-bone healing and provide a new possibility for improving the poor prognosis of rotator cuff surgery

Causal Relationships of General and Abdominal Adiposity on Osteoarthritis: A Two-Sample Mendelian Randomization Study

Background: Adiposity is closely related to osteoarthritis, but the causal effects of different types of adiposity on osteoarthritis are indistinct. This study conducted a Mendelian Randomization (MR) analysis for the causal effects of general adiposity and abdominal adiposity on knee osteoarthritis (KOA) and hip osteoarthritis (HOA). Methods: The general adiposity was assessed by body mass index (BMI), while the abdominal adiposity was evaluated with waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). The data used in this two-sample MR analysis originated from genome-wide association studies (GWAS). Significant (p −8) and independent (r2 p = 3.96 × 10−16) and HOA (OR: 1.412; 95% CI: from 1.196 to 1.666; p = 4.58 × 10−5). Additionally, WC and HC both positively and causally related to KOA (WC: OR: 1.827; 95% CI: from 1.564 to 2.134; p = 2.68 × 10−14; HC: OR: 1.610; 95% CI: from 1.357 to 1.912; p = 5.03 × 10−8) and HOA (WC: OR: 1.491; 95% CI: from 1.254 to 1.772; p = 5.85 × 10−6; HC: OR: 1.439; 95% CI: from 1.205 to 1.719; p = 5.82 × 10−5). However, no causal relationship existed between WHR and obesity. These results were robust according to the sensitivity analyses. Conclusions: This study indicated that both general and abdominal obesity had positive causal effects on knee osteoarthritis and hip osteoarthritis

The Burden of Rheumatoid Arthritis: Findings from the 2019 Global Burden of Diseases Study and Forecasts for 2030 by Bayesian Age-Period-Cohort Analysis

Background: Rheumatoid arthritis (RA) is a key health issue worldwide. Due to early identification and effective treatment strategies, the disease pattern of RA has also changed. However, the most comprehensive and up-to-date information about the burden of RA and its trends in subsequent years is lacking. Objective: this study aimed to report the global burden of RA by sex, age, region, and forecast for 2030. Method: Publicly available data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used in this study. The trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of RA from 1990 to 2019 were reported. The global burden of RA in 2019 was reported by a sex, age, and sociodemographic index (SDI). Finally, the trends in the following years were predicted by Bayesian age-period-cohort (BAPC) models. Results: Globally, the age-standardized prevalence rate increased from 207.46 (95% UI:189.99 to 226.95) in 1990 to 224.25 (95% UI: 204.94 to 245.99) in 2019, with an estimated annual percent change (EAPC) of 0.37% (95% CI: 0.32 to 0.42). Regarding the incidence, the age-standardized incidence rate (ASR) increased from 12.21 (95% UI: 11.13 to 13.38) to 13 (95% UI: 11.83 to 14.27) per 100,000 people from 1990 to 2019, with an EAPC of 0.3% (95% CI: 11.83 to 14.27). The age-standardized DALY rate also increased from 39.12 (95% UI: 30.13 to 48.56) per 100,000 people in 1990 to 39.57 (95% UI: 30.51 to 49.53) in 2019, with an EAPC of 0.12% (95% CI: 0.08% to 0.17%). There was no significant association between the SDI and ASR when the SDI was lower than 0.7, while there was a positive association between the SDI and ASR when the SDI was higher than 0.7 The BAPC analysis showed that the ASR was estimated to be up to 18.23 in females and approximately 8.34 per 100,000 people in males by 2030. Conclusion: RA is still a key public health issue worldwide. The global burden of RA has increased over the past decades and will continue to increase in the coming years, and much more attention should be given to early diagnosis and treatment to reduce the burden of RA

Metformin Treatment Reduces the Incidence of Rheumatoid Arthritis: A Two-Sample Mendelian Randomized Study

Several studies have shown that rheumatologic patients can benefit from metformin, but it remains unclear whether metformin treatment is causally associated with the risk of rheumatoid arthritis (RA). A two-sample Mendelian randomization (MR) study was conducted to investigate the causal relationship between metformin treatment and the incidence of rheumatoid arthritis. The genome-wide significant (p −8) single-nucleotide polymorphisms (SNPs) associated with metformin use were selected as instrumental variables (IVs). Summary statistics on RA were extracted from a large genome-wide association study (GWAS) meta-analysis. The inverse variance-weighted (IVW) method was used as the determinant of the causal effects of metformin treatment on RA. Cochran’s Q was used to detect heterogeneity. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression were used to detect horizontal pleiotropy. A total of 34 SNPs significantly associated with metformin treatment were obtained. Thirty-two SNPs were selected as IVs after removing two SNPs for being palindromic with intermediate allele frequencies (rs11658063 and rs4930011). The IVW results showed a negative causal association between metformin treatment and RA (OR = 0.0232, 95% CI 1.6046 × 10−3 − 0.3368; p = 0.006). Meanwhile, no heterogeneity or pleiotropy was detected, indicating that the results were reliable. This study indicated a negative causality between metformin treatment and RA, indicating that the treatment of metformin can prevent the pathogenesis of RA

Design and optimization of enzymatic activity in a de novo β-barrel scaffold

While native scaffolds offer a large diversity of shapes and topologies for enzyme engineering, their often unpredictable behavior in response to sequence modification makes de novo generated scaffolds an exciting alternative. Here we explore the customization of the backbone and sequence of a de novo designed eight stranded beta-barrel protein to create catalysts for a retro-aldolase model reaction. We show that active and specific catalysts can be designed in this fold and use directed evolution to further optimize activity and stereoselectivity. Our results support previous suggestions that different folds have different inherent amenability to evolution and this property could account, in part, for the distribution of natural enzymes among different folds.ISSN:1469-896XISSN:0961-836