Mechanism underlying synergic activation of Tyrosinase promoter by MITF and IRF4

Background: The transcription factor interferon regulatory factor 4 (IRF4) was identified to be involved in human pigmentation by genome-wide association studies (GWASs). The rs12203592-[T/C], which is located in intron 4 of IRF4, shows the strongest link to these pigmentation phenotypes including freckling, sun sensitivity, eye and hair color. Previous studies indicated a functional cooperation of IRF4 with Microphthalmia-associated transcription factor (MITF), a causing gene of Waardenburg syndrome (WS), to synergistically trans-activate Tyrosinase (TYR). However, the underlying mechanism is still unknown. Methods: To investigate the importance of DNA binding in the synergic effect of IRF4. Reporter plasmids with mutant TYR promoters was generated to locate the IRF4 DNA binding sites in the Tyrosinase minimal promoter. By building MITF and IRF4 truncated mutations plasmids, the necessary regions of the synergy functions of these two proteins were also located. Results: The cooperative effect between MITF and IRF4 was specific for TYR promoter. The DNA-binding of IRF4 was critical for the synergic function. IRF4 DNA binding sites in TYR promoter were identified. The Trans-activation domains in IRF4 (aa134-207, aa300-420) were both important for the synergic function, whereas the auto-mask domain (aa207-300) appeared to mask the synergic effect. Mutational analysis in MITF indicated that both DNA-binding and transcriptional activation domains were both required for this synergic effect. Conclusions: Here we showed that IRF4 potently synergized with MITF to activate the TYR promoter, which was dependent on DNA binding of IRF4. The synergic domains in both IRF4 and MITF were identified by mutational analysis. This identification of IRF4 as a partner for MITF in regulation of TYR may provide an important molecular function for IRF4 in the genesis of melanocytes and the pathogenic mechanism in WS

Evaluating the Impact of Construct Shift on Item Parameter Invariance, Test Equating and Proficiency Estimates

Common Core State Standards in English Language Arts and Mathematics at grades K to 12 were introduced in 2009 and at one time had been accepted by 45 of the states in the U.S. The new standards have created national curricula in these two subject areas. Along with this reform, new assessment systems have been developed too. Many of these new tests are showing signs of being more multidimensional than the tests they were replacing because of the use of new item formats, and the assessment of higher level thinking skills and various performance skills. In the short term at least, the new testing programs will still be using unidimensional IRT models because multidimensional IRT models are not well developed for wide-scale operational use. Test equating and proficiency estimates are likely to be influenced due to the violation of the unidimensionality assumption in the test data, which posed a threat to test fairness and the validity of score interpretations. Looking at the consequences of unidimensional models with multidimensional data is an important problem to investigate. In the first study, the potential effect of multidimensionality on item parameter invariance and IRT model fit at the item level was examined. The finding highlighted the fact that very modest changes in construct shift in the operational items of a test would not be problematic. As an extension of the first study, the second study introduced multidimensionality to a much greater magnitude and evaluated impact on IRT equating and proficiency estimates. It was found when construct shift occurred in the operational items, the impact was minimal in most aspects. Whereas, when construct shift occurred in the anchor and when these equating items were included in the total test, the influence of construct shift was quite substantial. The present research has provided evidence of consequences caused by construct shift as a function of the correlations between pairs of dimensions, the amount of shift, and where the shift occurs (equating or operational items). In general, it was found that construct shift had increasing impact as the amount of shift increased and the correlations between dimensions decreased

Complete sequences of KPC-2-encoding plasmid p628-KPC and CTX-M-55-encoding p628-CTXM coexisted in Klebsiella pneumoniae

A carbapenem-resistant Klebsiella pneumoniae strain 628 was isolated from a human case of intracranial infection in a Chinese teaching hospital. Strain 628 produces KPC-2 and CTX-M-55 encoded by two different conjugative plasmids, i.e., the IncFIIK plasmid p628-KPC and the IncI1 plasmid p628-CTXM, respectively. blaKPC-2 is captured by a Tn1721-based unit transposon with a linear structure ΔTn3-ISKpn27-blaKPC-2-ΔISKpn6-ΔTn1721, and this transposon together with a mercury resistance (mer) gene locus constitutes a 34 kb acquired drug-resistance region. blaKPC-2 has two transcription starts (nucleotides G and C located at 39 and 250 bp upstream of its coding region, respectively), which correspond to two promoters, i.e., the intrinsic P1 and the upstream ISKpn27/Tn3-provided P2 with the core -35/-10 elements TAATCC/TTACAT and TTGACA/AATAAT, respectively. blaCTX-M-55 is mobilized in an ISEcp1-blaCTX-M-55-Δorf477 transposition unit and appears to be the sole drug-resistant determinant in p628-CTXM. blaCTX-M-55 possesses a single transcription start (nucleotides G located at 116 bp upstream of its coding region), corresponding to the ISEcp1-provided P1 promoter with the core -35/-10 element TTGAAA/TACAAT. All the above detected promoters display a characteristic of constitutive expression. Coexistence of blaKPC and blaCTX-M in K. pneumoniae has been reported many times, but this is the first report to gain deep insights into genetic platforms, promoters, and expression of the two coexisted bla genes with determination of entire nucleotide sequences of the two corresponding plasmids

A Novel HVS-based Watermarking Scheme in Contourlet Transform Domain

In this paper, a novel watermarking technique in contourlet transform (CT) domain is presented. The proposed algorithm takes advantage of a multiscale framework and multi-directionality to extract the significant frequency, luminance and texture component in an image. Unlike the conventional methods in the contourlet domain, mask function is accomplished pixel by pixel by taking into account the frequency, the luminance and the texture content of all the image subbands including the low-pass subband and directional subbands. The adaptive nature of the novel method allows the scheme to be adaptive in terms of the imperceptibility and robustness. The watermark is detected by computing the correlation. Finally, the experimental results demonstrate the imperceptibility and the robustness against standard watermarking attacks. DOI: http://dx.doi.org/10.11591/telkomnika.v11i12.366

Ultra-high harmonic conversion of a seeded free-electron laser via harmonic optical klystron

External seeded free-electron lasers (FELs) are compelling tools for generating fully coherent EUV and soft X-ray radiations. Echo-enabled harmonic generation (EEHG), the most typical representative of external seeded FELs, has witnessed a remarkable growth of fully coherent FELs in the last decade, continuously evolving towards higher harmonic conversions and shorter wavelengths. Ultra-high harmonic generation is imperative in the field of FELs. This paper presents a novel method for generating FEL radiation with ultra-high harmonic conversion, utilizing harmonic optical klystron in combination with EEHG. This method can effectively increase the harmonic conversion order to about 90. Theoretical analysis and numerical simulations show that intense and almost fully coherent FEL pulses can be generated with a wavelength of 3 nm. At the same time, the seed laser intensity required by this scheme is lower compared to nominal EEHG, thus facilitating the generation of high-repetition-rate seeded FELs

Spatial network structure and driving factors of human settlements in three Northeastern provinces of China

IntroductionUrban human settlements' spatial network structures have emerged as crucial determinants impacting their health and sustainability. Understanding the influencing factors is pivotal for enhancing these settlements. This study focuses on 34 prefecture-level cities in Northeastern China from 2005 to 2020. It employs a modified gravitational model to establish spatial relationships among urban human settlements. Social network analysis techniques, including modularity and the quadratic assignment procedure (QAP) regression model, are introduced to analyze the network's characteristics and driving factors.MethodsA modified gravitational model is applied to create the spatial association network of urban human settlements. Social network analysis tools, along with modularity and the QAP regression model, are utilized to investigate the network's attributes and influencing elements. The study evaluates the evolution of spatial correlation, network cohesion, hierarchy, and efficiency.ResultsThroughout the study period, spatial correlation among urban human settlements in Northeastern China progressively intensified. However, the network exhibited relatively low density (0.217675), implying limited interconnectivity among cities. The average network hierarchy was 0.178225, indicating the need for optimization, while the average network efficiency was 0.714025, reflecting fewer redundant relationships. The analysis reveals the emergence of a polycentric network pattern with core and sub-core cities like Shenyang, Dalian, Changchun, Daqing, and Harbin. The urban network configuration has largely stabilized. The spatial association network showcases the intertwining of "small groups" and community organizations. Geographic proximity and merit-based linkages govern feature flow. Measures such as breaking administrative barriers, reducing flow time and distance, boosting resident income, and increasing government investment are identified to foster balanced network development and structural optimization.DiscussionThe research underscores the increasing spatial correlation and evolving network pattern among urban human settlements in Northeastern China. Despite the observed strengthening correlation, challenges related to network cohesion and hierarchy persist. The formation of a polycentric network signifies positive progress in urban development. The study highlights the importance of proximity and merit-based connections for feature flow. The proposed measures offer pathways to enhance network development and optimize structure, promoting holistic urban settlement growth and sustainability

Decoupling Degradations with Recurrent Network for Video Restoration in Under-Display Camera

Under-display camera (UDC) systems are the foundation of full-screen display devices in which the lens mounts under the display. The pixel array of light-emitting diodes used for display diffracts and attenuates incident light, causing various degradations as the light intensity changes. Unlike general video restoration which recovers video by treating different degradation factors equally, video restoration for UDC systems is more challenging that concerns removing diverse degradation over time while preserving temporal consistency. In this paper, we introduce a novel video restoration network, called D$^2$RNet, specifically designed for UDC systems. It employs a set of Decoupling Attention Modules (DAM) that effectively separate the various video degradation factors. More specifically, a soft mask generation function is proposed to formulate each frame into flare and haze based on the diffraction arising from incident light of different intensities, followed by the proposed flare and haze removal components that leverage long- and short-term feature learning to handle the respective degradations. Such a design offers an targeted and effective solution to eliminating various types of degradation in UDC systems. We further extend our design into multi-scale to overcome the scale-changing of degradation that often occur in long-range videos. To demonstrate the superiority of D$^2$RNet, we propose a large-scale UDC video benchmark by gathering HDR videos and generating realistically degraded videos using the point spread function measured by a commercial UDC system. Extensive quantitative and qualitative evaluations demonstrate the superiority of D$^2$RNet compared to other state-of-the-art video restoration and UDC image restoration methods. Code is available at https://github.com/ChengxuLiu/DDRNet.gitComment: AAAI 202