Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a ...disease-specific microsatellite. In the case of FXDs, the repeat unit is CGG/CCG and the repeat tract is located in the 5′ UTR of the X-linked FMR1 gene. Expansion can result in neurodegeneration, ovarian dysfunction, or intellectual disability depending on the number of repeats in the expanded allele. A growing body of evidence suggests that the mutational mechanisms responsible for many REDs share several common features. It is also increasingly apparent that in some of these diseases the pathologic consequences of expansion may arise in similar ways. It has long been known that many of the disease-associated repeats form unusual DNA and RNA structures. This review will focus on what is known about these structures, the proteins with which they interact, and how they may be related to the causative mutation and disease pathology in the FMR1 disorders.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A microconverter serves as a front-end dc-dc stage of a microinverter to convert the power from a photovoltaic module to a dc bus. These front-end microconverters require isolation, high-boost ratio, ...wide-input voltage regulation, and high efficiency. This paper introduces an isolated resonant converter with hybrid modes of operation to achieve wide-input regulation while still maintaining high efficiency. The proposed converter is designed as a series resonant converter with nominal-input voltage and operates under two additional modes: a boost converter with low-input voltage and a buck converter with high-input voltage. Unlike conventional resonant converters, this converter operates at discontinues conduction mode with a fixed frequency, simplifying the design and control. In addition, this converter can achieve zero-voltage switching (ZVS) and/or zero-current switching (ZCS) of the primary-side MOSFETs, ZVS and/or ZCS of the secondary-side MOSFETs, and ZCS of output diodes under all operating conditions. Experimental results using a 300-W prototype achieve a peak efficiency of 98.1% and a California Energy Commission efficiency of 97.6% including all auxiliary and control power at nominal-input voltage.
Perceptual image quality metrics have explicitly accounted for human visual system (HVS) sensitivity to subband noise by estimating just noticeable distortion (JND) thresholds. A recently proposed ...class of quality metrics, known as structural similarity metrics (SSIM), models perception implicitly by taking into account the fact that the HVS is adapted for extracting structural information from images. We evaluate SSIM metrics and compare their performance to traditional approaches in the context of realistic distortions that arise from compression and error concealment in video compression/transmission applications. In order to better explore this space of distortions, we propose models for simulating typical distortions encountered in such applications. We compare specific SSIM implementations both in the image space and the wavelet domain; these include the complex wavelet SSIM (CWSSIM), a translation-insensitive SSIM implementation. We also propose a perceptually weighted multiscale variant of CWSSIM, which introduces a viewing distance dependence and provides a natural way to unify the structural similarity approach with the traditional JND-based perceptual approaches.
The Fragile X-related disorders (FXDs) are Repeat Expansion Diseases resulting from an expansion of a CGG-repeat tract at the 5' end of the FMR1 gene. The mechanism responsible for this unusual ...mutation is not fully understood. We have previously shown that mismatch repair (MMR) complexes, MSH2/MSH3 (MutSβ) and MSH2/MSH6 (MutSα), together with Polβ, a DNA polymerase important for base excision repair (BER), are important for expansions in a mouse model of these disorders. Here we show that MLH1/MLH3 (MutLγ), a protein complex that can act downstream of MutSβ in MMR, is also required for all germ line and somatic expansions. However, exonuclease I (EXO1), which acts downstream of MutL proteins in MMR, is not required. In fact, a null mutation in Exo1 results in more extensive germ line and somatic expansions than is seen in Exo1+/+ animals. Furthermore, mice homozygous for a point mutation (D173A) in Exo1 that eliminates its nuclease activity but retains its native conformation, shows a level of expansion that is intermediate between Exo1+/+ and Exo1-/- animals. Thus, our data suggests that expansion of the FX repeat in this mouse model occurs via a MutLγ-dependent, EXO1-independent pathway, with EXO1 protecting against expansion both in a nuclease-dependent and a nuclease-independent manner. Our data thus have implications for the expansion mechanism and add to our understanding of the genetic factors that may be modifiers of expansion risk in humans.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The Repeat Expansion Diseases, a large group of human diseases that includes the fragile X-related disorders (FXDs) and Huntington's disease (HD), all result from expansion of a ...disease-specific microsatellite via a mechanism that is not fully understood. We have previously shown that mismatch repair (MMR) proteins are required for expansion in a mouse model of the FXDs, but that the FANCD2 and FANCI associated nuclease 1 (FAN1), a component of the Fanconi anemia (FA) DNA repair pathway, is protective. FAN1’s nuclease activity has been reported to be dispensable for protection against expansion in an HD cell model. However, we show here that in a FXD mouse model a point mutation in the nuclease domain of FAN1 has the same effect on expansion as a null mutation. Furthermore, we show that FAN1 and another nuclease, EXO1, have an additive effect in protecting against MSH3-dependent expansions. Lastly, we show that the loss of FANCD2, a vital component of the Fanconi anemia DNA repair pathway, has no effect on expansions. Thus, FAN1 protects against MSH3-dependent expansions without diverting the expansion intermediates into the canonical FA pathway and this protection depends on FAN1 having an intact nuclease domain.
A low-cost unidirectional dc/dc converter with galvanic isolation for fuel cell electric vehicles is presented in this article. To satisfy the requirements of the fuel cell stack and powertrain ...system of heavy-duty vehicles, three operation modes: boost, buck-boost, and buck, are proposed. To achieve ZVS operation for low voltage side switching devices, a novel platform current control mechanism is introduced. With the help of the platform current controller, the zero-voltage-switching operation is independent of the input/output voltage ratio. Meanwhile, the near zero-current-switching can be achieved for low voltage side switches under boost mode. The steady-state analyses and small-signal models for both input and platform currents under boost mode are provided. The prototype unit is built, and the corresponding experiments are presented.
We propose and experimentally demonstrate a high efficient circularly polarizing dichroism waveplate (CPDW) using a Si-based all-dielectric 2Dchiral metasurface. We demonstrate that the CPDW exhibits ...a unique dichroism in that it functions as a transmissive quarter waveplate for one of either left-or right-handed circularly polarized incident lightand a reflective mirror for the opposite polarization. The circular polarization dichroism (CPD = I
- I
) in transmission at wavelength ~1.5 μm reaches 97% and the extinction ratio (ER = I
/I
) is as high as 345:1. Experimental fabrications and measurements of the proposed all-dielectric metasurface are implemented and found to be in excellent agreement with the simulations. The proposed all-dielectric chiral metasurface is of advantages of high-dichroism, easy-fabrication and standard semiconductor fabrication techniques compatible, which could lead to enhanced security in fiber and free-space communications, as well as imaging and sensing applications for circularly polarized light with a highly integrated photonic platform.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Programmable magnetic field-free manipulation of perpendicular magnetization switching is essential for the development of ultralow-power spintronic devices. However, the magnetization in a ...centrosymmetric single-layer ferromagnetic film cannot be switched directly by passing an electrical current in itself. Here, we demonstrate a repeatable bulk spin-orbit torque (SOT) switching of the perpendicularly magnetized CoPt alloy single-layer films by introducing a composition gradient in the thickness direction to break the inversion symmetry. Experimental results reveal that the bulk SOT-induced effective field on the domain walls leads to the domain walls motion and magnetization switching. Moreover, magnetic field-free perpendicular magnetization switching caused by SOT and its switching polarity (clockwise or counterclockwise) can be reversibly controlled in the IrMn/Co/Ru/CoPt heterojunctions based on the exchange bias and interlayer exchange coupling. This unique composition gradient approach accompanied with electrically controllable SOT magnetization switching provides a promising strategy to access energy-efficient control of memory and logic devices.
Sarcoidosis is a multisystemic inflammatory and granulomatous disease that occurs in almost all populations and affects multiple organs. Meanwhile, its most common manifestation is pulmonary ...sarcoidosis. This study aimed to identify effective biomarkers for the diagnosis and therapy of pulmonary sarcoidosis.
GSE16538 was downloaded from Gene Expression Omnibus, including 6 pulmonary sarcoidosis samples and 6 normal lung samples. Then, differentially expressed genes (DEGs) were identified by limma package in R. After the expression values of the DEGs were extracted, hierarchical clustering analysis was performed for the DEGs using the pheatmap package in R. Subsequently, protein-protein interaction (PPI) pairs among the DEGs were searched by STRING or REACTOME databases, and then PPI networks were visualized by Cytoscape software. Using DAVID and KOBAS, functional and pathway enrichment analyses separately were performed for the DEGs involved in the PPI network.
Total 208 DEGs were identified in pulmonary sarcoidosis samples, including 179 up-regulated genes and 29 down-regulated genes. Hierarchical clustering showed that the DEGs could clearly distinguish the pulmonary sarcoidosis samples from the normal lung samples. In the PPI network constructed by STRING database, CXCL9, STAT1, CCL5, CXCL11 and GBP1 had higher degrees and betweenness values, and could interact with each other. Functional enrichment showed that CXCL9, CXCL11 and CCL5 were enriched in immune response. Moreover, STAT1 was enriched in pathways of chemokine signaling pathway and JAK-STAT signaling pathway.
CXCL9, CXCL11, STAT1, CCL5 and GBP1 might be implicated in pulmonary sarcoidosis through interacting with each other.
•There were 208 differentially expressed genes in pulmonary sarcoidosis samples.•CXCL9, CXCL11 and CCL5 were enriched in immune response and defense response.•CXCL9, CXCL11, STAT1, CCL5 and GBP1 might affect sarcoidosis via interactions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Salmonella spp. are one of the most important foodborne bacterial pathogens in human beings and animals. This study aimed to analyze the prevalence and characterization of Salmonella from broilers in ...Shandong, China. A total of 67 Salmonella were recovered from 600 rectal swabs collected from 3 large-scale intensive broiler farms (67/600, 11.2%) between May and October 2018. Among Salmonella isolates, the most common serovars were S. enteritidis and S. typhimurium. The highest occurrence of resistance observed was for polymyxin (100%), followed by ampicillin (68.7%). The multidrug-resistant Salmonella isolation rate was observed to be 53.7%. Four β-lactamase genes were detected among the isolates, and all the isolates carried blaTEM (67/67, 100%), followed by blaOXA (19/67, 28.4%), blaCTX-M (17/67, 25.4%), and blaPSE (7/67, 10.4%). Four plasmid-mediated quinolone resistance gene were detected among the isolates; the prevalent resistance genes was aac(6′)-Ib-cr (18/67, 26.9%), followed by oqxB (9/67, 13.4%), qnrB (6/67, 9.0%), and qnrD (1/67, 1.5%). The prevalent rate of mcr-1 was 6.0% (4/67). Class 1 integrons were detected in 26.9% of these isolates and contained 7 groups of resistance gene cassettes. Multilocus sequence typing analysis revealed 7 sequence types, and ST11 was the most frequent sequence types. This study indicated that reduction of Salmonella and strict control on the use of antibiotics in more than 5,000 million broilers in Shandong are the vitally important measures to keep public health.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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