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Summary: In natural long days, the florigen gene FLOWERING LOCUS T (FT) shows a bimodal expression pattern with morning and dusk peaks in Arabidopsis. This pattern differs from the one observed in the laboratory, and little is known about underlying mechanisms. A red : far‐red (R : FR) ratio difference between sunlight and fluorescent light causes this FT pattern mismatch.We showed that bimodal FT expression patterns were induced in a day longer than 14 h with sunlight R : FR (= c. 1) conditions. By circadian gating experiments, we found that cumulative exposure of R : FR‐adjusted light (R : FR ratio was adjusted to 1 with FR supplement) spanning from the afternoon to the next morning required full induction of FT in the morning. Conversely, only 2 h of R : FR adjustment in the late afternoon was sufficient for FT induction at dusk.We identified that phytochrome A (phyA) is required for the morning FT expression in response to the R : FR adjustment on the previous day. As a part of this mechanism, we showed that PHYTOCHROME‐INTERACTING FACTOR 7 contributes to FT regulation.Our results suggest that phyA‐mediated high‐irradiance response and the external coincidence mechanism contribute to morning FT induction under natural long‐day conditions. [ABSTRACT FROM AUTHOR]

Background: Biologics, regardless of whether they are biosimilars or reference products, are inherently variable due to their size, complexity, and the manufacturing process involved to produce them. Since a drift or evolution of quality attributes of a biologic may impact its clinical safety or efficacy, it is critical for the manufacturer to carefully control the manufacturing process and monitor the quality attributes of a biologic. Objective: The aim of this study was to demonstrate that the quality profile of the SB5 drug product has been consistent over its production history from 2013 to 2022. SB5 is a biosimilar referencing adalimumab (Humira, trademark of AbbVie Biotechnology Ltd) and SB5 has been approved by 14 regulatory authorities including the European Commission in August 2017 (brand name Imraldi™) and the US Food and Drug Administration in July 2019 (brand name Hadlima™). Methods: A total of 93 SB5 drug product batches manufactured between 2013 and 2022 were analyzed for a series of release parameters to evaluate the consistency in their critical quality attributes including purity, charge variants, and functional activities (TNF-α binding activity and TNF-α neutralizing potency). Results: The purity, charge variants, and functional activities of all batches were consistent over time and within the stringent acceptance criteria defined by regulatory agencies to ensure the safety and efficacy of SB5. Conclusion: The data presented in this study provide evidence that the quality of SB5 has remained consistent and tightly controlled even through process changes such as manufacturing site transfers and change in formulation. [ABSTRACT FROM AUTHOR]

As opposed to traditional fold-over flaps, where the tip of the flap is folded inward and then sutured into the nasal vestibule, here the distal flap was sutured first to the internal lining and folded outward. Because this defect was not extensive enough to warrant a forehead flap and involved primarily the right side of the nose, a two-stage procedure using an auricular cartilage graft and a fold-over melolabial interpolation flap was chosen to reconstruct the mucosal lining as well as the overlying soft tissue. A forehead flap would be preferable for larger defects.[2] However, a cheek-to-nose staged interpolation flap would work well to repair this unilateral medium-sized defect. [Extracted from the article]

Satellite dc–dc power converters are required to have electromagnetic interference (EMI) compatibility as well as high reliability. The requirement of high reliability limits the complexity of the structure as well as the number of low-reliability components. In this paper, a conventional active-clamp-forward (ACF) topology is examined for a satellite converter owing to its relatively simple structure, small number of components, and good clamping capability regarding its switch voltage stress. However, it has a pulsating input current shape, a high di/dt level, and high switch voltage stress, which are disadvantageous with regard to the EMI filter size and high-input-voltage converter applications. To overcome these drawbacks, a new ACF topology with a continuous input current waveform is proposed. In the proposed waveform, the voltage stresses on the main switches are relieved, which is crucial to ensure the reliability of satellite FET switches, by utilizing a two-series connected structure. These features allow the proposed converter to serve as a high-input-voltage, high power-density satellite converter. In this paper, 100 W prototype converters with 50 V inputs operating at 300 kHz are built with a high power density of 47.9 W/in3. Experiments on these prototype converters are carried out to verify the features. [ABSTRACT FROM AUTHOR]

An improved data rate technology from tag to reader in Wi-Fi backscatter systems is proposed. The proposed system applies a power-level modulation to the conventional backscatter communication system. This technology can improve the data rate dramatically. It also adopts the Euclidean distance evaluation during demodulation, which looks for the most similar signal to enhance the BER performance. We analyze the error performance of the proposed decoding method, and the numerical results are presented. The power level is formed ranging from 2-level to 8-level. The performance of the detecting algorithm is compared to the conventional system, which utilizes the received power of selected sub-carriers. [ABSTRACT FROM AUTHOR]

A screening process for the germination and growth of seed is generally required for plant research. Such a repetitive screening process is costly and time-consuming, and its bulky setup requires a lot of space. In particular, the control of the variables, such as light, nutrients, hormones and temperature, is difficult due to the limited space for incubation. In addition, small seeds such as Arabidopsis thaliana are difficult to handle as they are hundreds of microns in diameter and require a more precisely controllable screening environment. However, conventional screening methods involve the seeding of multiple seeds on a single agarose plate without physical partitions. Such methods need to be improved because they lack control over the growth environment and the results are highly dependent on the researchers. To overcome the above-mentioned limitations, a novel seeding array chip has been developed which can be filled with conventional solid agarose while enabling more efficient screening. Individual seeds can be partitioned from each other and a number of different agarose conditions can be tested in a single plant array chip. As a demonstration, we tested the effect of various concentrations of Murashige and Skoog medium and a plant hormone (e.g., abscisic acid) on the growth of Arabidopsis. The chip can efficiently save the space required for screening by providing different conditions for ∼400 seeds in a 59 × 55 mm chip, and it also provides easy observation and analysis of seed growth. The proposed plant array chip is expected to contribute to more efficient screening of essential phenotypes such as germination and growth for both academic and industrial purposes. [ABSTRACT FROM AUTHOR]

Phytochromes are red and far-red light photoreceptors that regulate the responses of plants to light throughout their life cycles. Phytochromes do this in part by inhibiting the function of a group of basic helix-loop-helix transcription factors called phytochrome-interacting factors (PIFs). Arabidopsis has eight PIFs that function sometimes redundantly and sometimes distinctively depending on their expression patterns and protein stability, as well as on variations in the promoters they target in vivo . PIF-like proteins exist in other seed plants and non-vascular plants where they also regulate light responses. The mechanism by which phytochrome regulates light responses by promoting the degradation of the PIFs is conserved in liverwort, suggesting it must have evolved some time before the last common ancestor shared by seed plants and non-vascular plants. [ABSTRACT FROM AUTHOR]

[Display omitted] • Framework for real-time RNN with PCA was developed for time-series prediction of hydrate formation dynamics. • ARLSTM models showed the best prediction for hydrate transition and sloughing events. • Transfer learning enhanced the predictive accuracy under specific environments. Preventing gas hydrate formation is critical in offshore gas and oil production systems. Several models can predict hydrate formation, however, these empirical approaches have limitations due to dependency on geometries and fluid characteristics of the systems. The trends of hydrate formation or risk are considered statistical, which means there is no definite model to describe its behavior. Herein, we present a novel framework based on a combination of feature reduction methods and several deep learning models to predict the hydrate formation trend through the multivariate sensor data. Transition and segregation trends during hydrate formation were predicted in real-time using sequential time series data from the last 60 s. We employed various deep learning models (Dense, LSTM, GRU, ARLSTM), layers, and dropout to investigate and enhance the prediction ability of each model. Two groups of experimental data (200 rpm, 600 rpm) were used for training and testing the prediction to examine the universal applicability of the model. Transfer learning in training the model was employed to apply the discrete experimental set into time-series data and enhance the accuracy. The results with higher layer numbers and a dropout rate of 0.2 ∼ 0.6 showed the best performance. ARLSTM showed the smallest error among deep learning models and predicted the good trend of kinetic characteristics (transition and segregation part) during the hydrate formation. This approach based on deep learning can be adopted for risk and issue detection of pipelines in the gas production system. [ABSTRACT FROM AUTHOR]

PHYTOCHROME-INTERACTING FACTOR1 (PIF1) is a basic helix-loop-helix transcription factor that inhibits light-dependent seed germination in Arabidopsis thaliana. However, it remains unclear whether PIF1 requires other factors to regulate its direct targets. Here, we demonstrate that LEUNIG_HOMOLOG (LUH), a Groucho family transcriptional corepressor, binds to PIF1 and coregulates its targets. Not only are the transcriptional profiles of the luh and pif1 mutants remarkably similar, more than 80% of the seeds of both genotypes germinate in the dark. We show by chromatin immunoprecipitation that LUH binds a subset of PIF1 targets in a partially PIF1-dependent manner. Unexpectedly, we found LUH binds and coregulates not only PIF1-activated targets but also PIF1-repressed targets. Together, our results indicate LUH functions with PIF1 as a transcriptional coregulator to inhibit seed germination. [ABSTRACT FROM AUTHOR]

Skutterudite compounds have been studied as potential thermoelectric materials due to their high thermoelectric efficiency, which makes them attractive candidates for applications in thermoelectric power generation. In this study, the effects of double-filling on the thermoelectric properties of the CexYb0.2−xCo4Sb12 skutterudite material system were investigated through the process of melt spinning and spark plasma sintering (SPS). By replacing Yb with Ce, the carrier concentration was compensated for by the extra electron from Ce donors, leading to optimized electrical conductivity, Seebeck coefficient, and power factor of the CexYb0.2−xCo4Sb12 system. However, at high temperatures, the power factor showed a downturn due to bipolar conduction in the intrinsic conduction regime. The lattice thermal conductivity of the CexYb0.2−xCo4Sb12 skutterudite system was clearly suppressed in the range between 0.025 and 0.1 for Ce content, due to the introduction of the dual phonon scattering center from Ce and Yb fillers. The highest ZT value of 1.15 at 750 K was achieved for the Ce0.05Yb0.15Co4Sb12 sample. The thermoelectric properties could be further improved by controlling the secondary phase formation of CoSb2 in this double-filled skutterudite system. [ABSTRACT FROM AUTHOR]

There is controversy regarding the optimal surgical modality and ideal recommended margins for treating melanoma in situ (MIS) and invasive melanoma (IM). Although wide local excision is recommended, staged excision offers excellent margin control and low recurrence rates. In this manuscript, we reviewed a 10-year experience of staged excisions for the treatment of MIS and IM. A retrospective review was performed of 130 MIS and 32 IM cases treated with staged excision from April 2012 to April 2022. Staged excision was performed on the head and neck in 102 (79%) MIS and 23 (72%) IM cases. Approximately 10% of cases required surgical margins above the current recommendations (11 (9%) MIS and 6 (19%) IM). Twenty-three (19%) MIS and 7 (22%) IM cases required more than one excision to obtain clearance. Recurrence rates among MIS and IM were 0.0% and 0.6%, respectively. Upstaging occurred in 5 (4%) MIS and 7 (22%) IM cases. Complex repairs were performed on 82 (63%) MIS and 17 (53%) IM cases. Our findings revealed that staged excision provides effective margin control and low recurrence rates. Approximately 10% of patients required margins greater than the current recommendations, leading to larger defects and more complex repairs. [ABSTRACT FROM AUTHOR]

A case study of a 53-year-old man with a history of pemphigus foliaceus (PF) is presented, with acute lower back pain. It mentions the patient was diagnosed with Immunoglobulin G-mediated PF with an elevated serum autoantibody index against desmoglein. It also discusses need of improving detection of underlying malignancy.

A methodology for evaluating risks at nuclear facilities is developed in this work. A series of measures is drawn from the analysis of factors that determine risks. Five measures are created to evaluate risks at nuclear facilities. These include the legal and institutional framework, material control, physical protection system effectiveness, human resources, and consequences. Evaluation attributes are developed for each measure and specific values are given in order to calculate the risk value quantitatively. Questionnaires are drawn up on whether or not a state has properly established a legal and regulatory framework (based on international standards). These questionnaires can be a useful measure for comparing the status of the physical protection regime between two countries. Analyzing an insider threat is not an easy task and no methodology has been developed for this purpose. In this study, attributes that could quantitatively evaluate an insider threat, in the case of an unauthorized removal of nuclear materials, are developed by adopting the Nuclear Material Accounting & Control (NMAC) system. The effectiveness of a physical protection system, P ( E ), could be analyzed by calculating the probability of interruption, P ( I ), and the probability of neutralization, P ( N ). In this study, the Tool for Evaluating Security System (TESS) code developed by KINAC is used to calculate P ( I ) and P ( N ). Consequence is an important measure used to analyze risks at nuclear facilities. This measure comprises radiological, economic, and social damage. Social and economic damages are difficult to evaluate. Therefore, radiation levels and theft of nuclear materials that could be quantified are adopted as attributes for analyzing the consequences. Awareness of the nuclear security culture and physical protection resources such as staffing, capabilities, and cost required to provide PP should be considered when evaluating risks. In this study, these attributes are included in the measure of human resources. Human resources include such factors as trustworthiness, degree of nuclear security culture awareness, and frequency of psychiatric testing of employees. A case study performed on hypothetical facilities demonstrates that the developed methodology could be used to analyze innovative nuclear systems as well as existing facilities. [ABSTRACT FROM AUTHOR]

Phytochrome-interacting factor 1 (PIF1) inhibits light-dependent seed germination. The specific function of PIF1 in seed germination is partly due to its high level of expression in imbibed seeds, but the associated regulatory factors have not been identified. Here we show that mutation of the early flowering in short days (EFS) gene, encoding an H3K4 and H3K36 methyltransferase, decreases the level of H3K36me2 and H3K36me3 but not H3K4me3 at the PIF1 locus, reduces the targeting of RNA polymerase II to the PIF1 locus, and reduces mRNA expression of PIF1 in imbibed seeds. Consistently, the efs mutant geminated even under the phyBoff condition, and had an expression profile of PIF1 target genes similar to that of the pif1 mutant. Introduction of an EFS transgene into the efs mutant restored the level of H3K36me2 and H3K36me3 at the PIF1 locus, the high-level expression of PIF1 mRNA, the expression pattern of PIF1 target genes, and the light-dependent germination of these seeds. Introduction of a PIF1 transgene into the efs mutant also restored the expression pattern of PIF1 target genes and light-dependent germination in imbibed seeds, but did not restore the flowering phenotype. Taken together, our results indicate that EFS is necessary for high-level expression of PIF1 mRNA in imbibed seeds. [ABSTRACT FROM AUTHOR]

A previous study showed that SOMNUS (SOM), which encodes a C3H-type zinc finger protein, is a key negative regulator of seed germination that acts downstream of PHYTOCHROME INTERACTING FACTOR3-LIKE5 (PIL5). However, it was not determined if PIL5 is the sole regulator of SOM expression. Public microarray data suggest that the expression of SOM mRNA is regulated also by ABSCISIC ACID INSENSITIVE3 (ABI3), another key regulator of seed germination. By analyzing abi3 mutants and ABI3 overexpression lines, we show here that ABI3 activates the expression of SOM mRNA collaboratively with PIL5 in imbibed seeds. Chromatin immunoprecipitation analysis coupled with electrophoretic mobility shift assay indicate that ABI3 activates the expression of SOM mRNA by directly binding to two RY motifs present in the SOM promoter in vivo, which is further supported by the greatly decreased expression of a reporter gene driven by a SOM promoter bearing mutated RY motifs. At the protein level, the ABI3 protein interacts with the PIL5 protein. The ABI3-PIL5 interaction, however, does not affect targeting of ABI3 and PIL5 to SOM promoters. Taken together, our results indicate that ABI3 and PIL5 collaboratively activate the expression of SOM mRNA by directly binding to and interacting with each other at the SOM promoter. [ABSTRACT FROM AUTHOR]

Abstract: Ciguatera is a global food poisoning caused by the consumption of fish that have accumulated sodium channel activator toxins, ciguatoxins. At present, most diagnosed cases of ciguatera are treated with symptomatic and supportive remedies, and no specific therapy has been devised. Here we report that ciguatoxin CTX3C can be effectively neutralized in vitro and in vivo by simultaneous use of two anti-ciguatoxin monoclonal antibodies, providing the first rational approach toward directly preventing and treating ciguatera. [Copyright &y& Elsevier]

In order to flower in the appropriate season, plants monitor light and temperature changes and alter downstream pathways that regulate florigen genes such as Arabidopsis (Arabidopsis thaliana) FLOWERING LOCUS T (FT). In Arabidopsis, FT messenger RNA levels peak in the morning and evening under natural long‐day conditions (LDs). However, the regulatory mechanisms governing morning FT induction remain poorly understood. The morning FT peak is absent in typical laboratory LDs characterized by high red:far‐red light (R:FR) ratios and constant temperatures. Here, we demonstrate that ZEITLUPE (ZTL) interacts with the FT repressors TARGET OF EATs (TOEs), thereby repressing morning FT expression in natural environments. Under LDs with simulated sunlight (R:FR = 1.0) and daily temperature cycles, which are natural LD‐mimicking environmental conditions, FT transcript levels in the ztl mutant were high specifically in the morning, a pattern that was mirrored in the toe1 toe2 double mutant. Low night‐to‐morning temperatures increased the inhibitory effect of ZTL on morning FT expression by increasing ZTL protein levels early in the morning. Far‐red light counteracted ZTL activity by decreasing its abundance (possibly via phytochrome A (phyA)) while increasing GIGANTEA (GI) levels and negatively affecting the formation of the ZTL–GI complex in the morning. Therefore, the phyA‐mediated high‐irradiance response and GI play pivotal roles in morning FT induction. Our findings suggest that the delicate balance between low temperature‐mediated ZTL activity and the far‐red light‐mediated functions of phyA and GI offers plants flexibility in fine‐tuning their flowering time by controlling FT expression in the morning. [ABSTRACT FROM AUTHOR]

Abstract Amidst entertainment market uncertainties, cross-medium content extension has emerged as a powerful strategy. Webtoons, digital cartoons, stand out as significant resources. However, limited research has delved into effective strategies for extending these narratives. Acknowledging the crucial role of evoking viewer emotions in content success, this study investigates viewer emotional responses. Departing from conventional methods, we employ neuroscientific measurement—specifically, electroencephalography (EEG)—to capture real-time viewer emotions during content consumption, assessing valence and arousal. We examine the impact of webtoon-drama similarity on viewer emotions and scene attributes that heighten emotional responses. By integrating EEG data, interview insights, and scene analysis, our findings underscore intensified emotions when drama scenes mirror webtoon elements, particularly in sets and directing. Effective replication relies on drama-specific attributes such as choreography, original soundtracks, and casting. This study contributes academically by using EEG to evaluate webtoons’ value as original sources and practically by offering concrete webtoon extension strategy. [ABSTRACT FROM AUTHOR]

BACKGROUND Electroabrasion, which uses an in-office electrosurgical device, is a method of surgical planning that ablates the skin to the papillary dermis. Several reports demonstrate that intraoperative ablative interventions with lasers or dermabrasion can modulate scar formation more effectively. This investigation uses electroabrasion intraoperatively to mitigate scar formation. OBJECTIVE To evaluate the effectiveness of intraoperative electroabrasion for scar revision. MATERIALS AND METHODS This was a prospective, randomized, observer-blinded, split-scar study with 24 linear scar segments resulting from primary closures in patients undergoing Mohs micrographic surgery. After placement of dermal sutures, half of the wound was randomly treated with electroabrasion. The other half was used as the control. Scar appearance was assessed by a blinded observer and by the patient using the Patient and Observer Scar Assessment Scale at 1 to 2 weeks, 1 month, and 3 months after surgery. RESULTS At the 3-month follow-up, both patient and observer variables measuring scar contour improved on the treated side, whereas erythema was worse. Overall, no difference was seen in total scores between the 2 sides. CONCLUSION Based on this pilot study, scars treated with electroabrasion revealed improved surface topography but worsened erythema. Future studies with more refined electrosurgical settings are needed for further evaluation. [ABSTRACT FROM AUTHOR]

This paper evaluates the dv/dt performances of the motor input terminal fed by a gallium nitride (GaN) field effect transistor (FET) matrix converter for variable frequency drive applications. To limit the high dv/dt caused by the fast switching operation of GaN devices, a dv/dt filter is employed. With the dv/dt filter, the input terminal voltage can meet the standards suggested by National Electrical Manufacturers Association. On the other hand, when a GaN FET matrix converter and an electric motor are connected by a long cable, the parasitic impedance of the cable varies. This impedance mismatch results in voltage reflection (VR), and this VR causes a large surge voltage with severe ringing at the motor input terminal. Even in this case, the dv/dt filter effectively restricts the dv/dt of the voltage applied to the electric motor. Frequency response results are obtained through the transfer functions of the filter according to the applied position. Experiments are carried out using a 220 V/60 Hz induction motor and a GaN FET-based matrix converter prototype. The dv/dt filter performance with two positions and cable lengths of 5 m and 25 m is evaluated by comparing the obtained experimental results with the frequency response. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin is a typical anticancer drug that causes cardiomyopathy and heart failure (HF). The aim of our study was to investigate incidence, risk factors for doxorubicin‐induced HF in Korean cancer patients and their survival rate, utilizing a nationwide population‐based cohort. Methods: We analyzed 58 541 cancer patients who received doxorubicin between 2003 and 2010. Descriptive analysis was performed in patients with breast cancer, hematologic malignancy, gynecological malignancy, and sarcoma. Risk factors associated with doxorubicin‐induced HF were investigated using a Cox proportional hazards model. The survival rate of doxorubicin‐induced HF patients was compared with that of patients without doxorubicin‐induced HF. Results: A total of 2324 (4%) were diagnosed with doxorubicin‐induced HF. In patients with breast cancer, predictive risk factors for doxorubicin‐induced HF included age over 65 years [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.05‐1.72], hypertension [HR 2.45 (2.12‐ 2.84)], diabetes mellitus [HR 1.26 (1.05‐1.51)], coronary artery disease [HR 2.08 (1.63‐2.66)], advanced stage [HR 1.31 (1.13‐1.50)], and trastuzumab administration [HR 2.94 (2.54‐3.40)]. In patients with hematologic malignancy, predictive risk factors included age over 65 years [HR 1.75 (1.49‐2.07)], hypertension [HR 1.62 (1.37‐1.92)], and coronary artery disease [HR 2.28 (1.80‐2.89)]. Five‐year survival rates of patients with doxorubicin‐induced HF were significantly lower relative to those of patients without HF in breast cancer and hematologic malignancy: 80% vs 84% and 69% vs 75%, respectively (P < 0.001). Conclusions: In cancer patients treated with doxorubicin, management of risk factors, early detection, and treatment for doxorubicin‐induced HF might be critical for patient survival. In cancer patients treated with doxorubicin, management of risk factors, early detection, and treatment for doxorubicin‐induced HF might be critical for patient survival. Because the data from Asian population in terms of cardio‐oncology are scarce, our study tried to fill that gap. [ABSTRACT FROM AUTHOR]

Nasal reconstruction has important functional and cosmetic considerations, as proper repair of nasal defects is necessary to maintain function of the nasal airway and to recreate the normal appearance of this central facial structure. Cheek advancement flaps provide matched, mobile, and highly vascularized tissue for the reconstruction of nasal defects, allowing for the concealment of incisions within natural creases in a one-stage approach. However, cheek advancement flaps are often underutilized for nasal reconstruction because of their difficulty in restoring nasal contour. We describe reconstruction of 19 nasal dorsal and sidewall defects 0.8 to 3 cm in size. We incorporated a periosteal anchoring suture to maintain/restore nasal contour and additionally removed a half standing cone inferior to the defect to prevent encroachment of the nasal ala or alar crease. All patients were evaluated at least 3 months postoperatively. In all patients, we were able to restore concavity of the nasofacial sulcus, preserve the biconvex nasal tips, prevent alar flaring and retraction, and conserve the alar groove. All patients had excellent functional and cosmetic outcomes. We believe this modified cheek advancement flap provides functionally and aesthetically superior results and can be considered as a first-line approach for repair of nasal dorsal and sidewall defects in subselected patients. [ABSTRACT FROM AUTHOR]

Inappropriate information on a deadly and rare disease can make people vulnerable to problematic decisions, leading to irreversible bad outcomes. This study explored online information exchanges on pancreatic cancer. We collected 35,596 questions and 83,888 answers related to pancreatic cancer from January 1, 2003 to May 31, 2020, from Naver, the most popular Korean web portal. We also collected 8495 news articles related to pancreatic cancer during the same period. The study methods employed were structural topic modeling, keyword frequency analysis, and qualitative coding of medical professionals. The number of questions and news articles increased over time. In Naver's questions, topics on symptoms and diagnostic tests regarding pancreatic cancer increased in proportion. The news topics on new technologies related to pancreatic cancer from various companies increased as well. The use of words related to back pain—which is not an important early symptom in pancreatic cancer—and biomarker tests using blood increased over time in Naver's questions. Based on 100 question samples related to symptoms and diagnostic tests and an analysis of the threaded answers' appropriateness, there was considerable misinformation and commercialized information in both categories. [ABSTRACT FROM AUTHOR]

Seeds monitor the environment to germinate at the proper time, but different species respond differently to environmental conditions, particularly light and temperature. In Arabidopsis thaliana , light promotes germination but high temperature suppresses germination. We previously reported that light promotes germination by repressing SOMNUS (SOM). Here, we examined whether high temperature also regulates germination through SOM and found that high temperature activates SOM expression. Consistent with this, som mutants germinated more frequently than the wild type at high temperature. The induction of SOM mRNA at high temperature required abscisic acid (ABA) and gibberellic acid biosynthesis, and ABA-INSENSITIVE3 (ABI3), ABI5, and DELLAs positively regulated SOM expression. Chromatin immunoprecipitation assays indicated that ABI3, ABI5, and DELLAs all target the SOM promoter. At the protein level, ABI3, ABI5, and DELLAs all interact with each other, suggesting that they form a complex on the SOM promoter to activate SOM expression at high temperature. We found that high-temperature-inducible genes frequently have RY motifs and ABA -responsive elements in their promoters, some of which are targeted by ABI3, ABI5, and DELLAs in vivo. Taken together, our data indicate that ABI3, ABI5, and DELLAs mediate high-temperature signaling to activate the expression of SOM and other high-temperature-inducible genes, thereby inhibiting seed germination. [ABSTRACT FROM AUTHOR]

Amyloid beta (Aβ) peptide, one of the most important pathogenic traits of Alzheimer's disease (AD), invokes a cascade of oxidative damage and eventually leads to neuronal death. In the present study, baicalein, wogonin, and oroxylin A, main active flavones in Scutellaria baicalensis, were evaluated for their neuroprotective effects against Aβ25–35-stimulated damage. All tested compounds decreased Aβ25–35-induced ROS generation and cell cycle arrest. In particular, baicalein exhibited the strongest antioxidant activity. In addition, these compounds suppressed apoptosis by attenuating mitochondrial dysfunction such as loss of membrane potential, Ca2+ accumulation and Bax/Bcl-2 ratio. Furthermore, all tested flavones inhibited the expression of iNOS and COX-2, which resulted in suppressing inflammatory cytokines including TNF-α, NO, and PGE2. Noticeably, all compounds exhibited the anti-inflammatory effects through downregulating NF-κB/MAPK pathway. Especially, oroxylin A was effective against both p65 and IκBα, while wogonin and baicalein were suppressed phospho-p65 and phospho-IκBα, respectively. Taken together, baicalein, wogonin, and oroxylin A can effectively relieve Aβ25–35-stimulated neuronal apoptosis and inflammation in PC12 cells via downregulating NF-κB/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Coral reefs composed of stony corals are threatened by global marine environmental changes. However, soft coral communities of octocorallian species, appear more resilient. The genomes of several cnidarians species have been published, including from stony corals, sea anemones, and hydra. To fill the phylogenetic gap for octocoral species of cnidarians, we sequenced the octocoral, Dendronephthya gigantea, a nonsymbiotic soft coral, commonly known as the carnation coral. The D. gigantea genome size is ∼276 Mb. A high-quality genome assembly was constructed from PacBio long reads (29.85 Gb with 108× coverage) and Illumina short paired-end reads (35.54 Gb with 128× coverage) resulting in the highest N50 value (1.4 Mb) reported thus far among cnidarian genomes. About 12% of the genome is repetitive elements and contained 28,879 predicted protein-coding genes. This gene set is composed of 94% complete BUSCO ortholog benchmark genes, which is the second highest value among the cnidarians, indicating high quality. Based on molecular phylogenetic analysis, octocoral and hexacoral divergence times were estimated at 544 MYA. There is a clear difference in Hox gene composition between these species: unlike hexacorals, the Antp superclass Evx gene was absent in D. gigantea. Here, we present the first genome assembly of a nonsymbiotic octocoral, D. gigantea to aid in the comparative genomic analysis of cnidarians, including stony and soft corals, both symbiotic and nonsymbiotic. The D. gigantea genome may also provide clues to mechanisms of differential coping between the soft and stony corals in response to scenarios of global warming. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66-year-old man, who was admitted for patch testing due to the development of an itchy rash affecting his upper back and posterior upper arms. He underwent clinical examination which indicated many pink to skin-coloured papules coalescing into plaques. The patient was suspected to have fibreglass dermatitis, which is mostly observed in fishermen and surfers who sit in old boats or ride a surfboard without a wetsuit.

Many open form (OF) structures of drug targets were obtained a posteriori by analysis of co-crystals with inhibitors. Therefore, obtaining the OF structure of a drug target a priori will accelerate development of potent inhibitors. In addition to its small active site, Trypanosoma cruzi dihydroorotate dehydrogenase (TcDHODH) is fully functional in its monomeric form, making drug design approaches targeting the active site and protein-protein interactions unrealistic. Therefore, a novel a priori approach was developed to determination the TcDHODH active site in OF. This approach consists of generating an "OF inducer" (predicted in silico) to bind the target and cause steric repulsion with flexible regions proximal to the active site that force it open. We provide the first proof-of-concept of this approach by predicting and crystallizing TcDHODH in complex with an OF inducer, thereby obtaining the OF a priori with its subsequent use in designing potent and selective inhibitors. Fourteen co-crystal structures of TcDHODH with the designed inhibitors are presented herein. This approach has potential to encourage drug design against diseases where the molecular targets are such difficult proteins possessing small AS volume. This approach can be extended to study open/close conformation of proteins in general, the identification of allosteric pockets and inhibitors for other drug targets where conventional drug design approaches are not applicable, as well as the effective exploitation of the increasing number of protein structures deposited in Protein Data Bank. [ABSTRACT FROM AUTHOR]

Mutations in Phytochrome Interacting Factors (PIFs) induce a conversion of the endodermal amyloplasts necessary for gravity sensing to plastids with developed thylakoids accompanied by abnormal activation of photosynthetic genes in the dark. In this study, we investigated how PIFs regulate endodermal plastid development by performing comparative transcriptome analysis. We show that both endodermal expression of PIF1 and global expression of the PIF quartet induce transcriptional changes in genes enriched for nuclear-encoded photosynthetic genes such as LHCA and LHCB . Among the 94 shared differentially expressed genes identified from the comparative transcriptome analysis, only 14 genes are demonstrated to be direct targets of PIF1, and most photosynthetic genes are not. Using a co-expression analysis, we identified a direct target of PIF, whose expression pattern shows a strong negative correlation with many photosynthetic genes. We have named this gene REPRESSOR OF PHOTOSYNTHETIC GENES1 ( RPGE1 ). Endodermal expression of RPGE1 rescued the elevated expression of photosynthetic genes found in the pif quadruple ( pifQ ) mutant and partly restored amyloplast development and hypocotyl negative gravitropism. Taken together, our results indicate that RPGE1 acts downstream of PIF1 in the endodermis to repress photosynthetic genes and regulate plastid development. [ABSTRACT FROM AUTHOR]

In this work, we investigate the influence of a chlorine-based electro-chemical surface treatment on the characteristics of indium tin oxide (ITO) including the work function, chemical composition, and phase transition. The treated ITOs were characterized using X-ray photoelectron spectroscopy (XPS), ultra-violet photoelectron spectroscopy (UPS), 4-point probe measurements, and grazing incidence X-ray diffraction (GI-XRD). We confirmed a change of the chemical composition in the near-surface region of the ITO and the formation of indium-chlorine (In-Cl) bonds and surface dipoles (via XPS). In particular, the change of the electro-static potential in the outer surface was caused by chlorination. Due to the vacuum-level shift after the electro-chemical treatment in a dilute hydrochloric acid, the ITO work function was increased by ∼0.43 eV (via UPS); furthermore, the electro-negativity of the chlorine anions attracted electrons to emit them from the hole transport layer (HTL) to the ITO anodes, resulting in an increase of the hole-injection efficiency. [ABSTRACT FROM AUTHOR]

The bHLH transcription factor PHYTOCHROME INTERACTING FACTOR1 (PIF1) binds G-box elements in vitro and inhibits light-dependent germination in Arabidopsis thaliana. A previous genome-wide analysis of PIF1 targeting indicated that PIF1 binds 748 sites in imbibed seeds, only 59% of which possess G-box elements. This suggests the G-box is not the sole determinant of PIF1 targeting. The targeting of PIF1 to specific sites could be stabilized by PIF1-interacting transcription factors (PTFs) that bind other nearby sequence elements. Here, we report PIF1 targeting sites are enriched with not only G-boxes but also with other hexameric sequence elements we named G-box coupling elements (GCEs). One of these GCEs possesses an ACGT core and serves as a binding site for group A bZIP transcription factors, including ABSCISIC ACID INSENSITIVE5 (ABI5), which inhibits seed germination in abscisic acid signaling. PIF1 interacts with ABI5 and other group A bZIP transcription factors and together they target a subset of PIF1 binding sites in vivo. In vitro single-molecule fluorescence imaging confirms that ABI5 facilitates PIF1 binding to DNA fragments possessing multiple G-boxes or the GCE alone. Thus, we show in vivo PIF1 targeting to specific binding sites is determined by its interaction with PTFs and their binding to GCEs. [ABSTRACT FROM AUTHOR]

Summary Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. Mechanistically, the melanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Background: Community care is a care model with the aim of shifting care services from being hospital based toward community-based care. Advances in platforms based on information and communications technology (ICT) with a person-centered approach provide the potential to improve the delivery of health and social care services toward community-based settings.Objectives: The aims of this study were to describe the ICT-Based Person-Centered Community Care Platform (IPC3P) and to determine its impact on health- and social-care-related shared decision-making and quality of life among community residents.Methods: An online platform was developed with the aim of enhancing community care. The platform had four components: (1) comprehensive health and social needs assessment system, (2) personalized community care planning, (3) needs-based health and social care services delivery, and (4) health community engagement. Community residents were invited to use and evaluate the impact of the IPC3P on their quality of life and shared decision-making regarding health and social care services. They provided feedback about the platform by completing two surveys: at baseline (before using the platform) and 6 months after using the platform.Results: Data of 164 community residents were analyzed in this study. Between baseline and after using the platform, the quality of life reported by the participants increased significantly in all domains, with clear improvements also noted for shared decision-making about health and social care services. The IPC3P received positive feedback from the participants for its usability, familiarity, and ease of use. Some participants also reported their desire for the addition of more functions that support health communities.Conclusion: The IPC3P has the potential to enhance the involvement of community residents in their own care. The findings of this study can be used to support the wider implementation of the IPC3P to promote person-centered community care. [ABSTRACT FROM AUTHOR]

Seed dormancy, a seed status that prohibits germination even in the presence of inductive germination signals, is a poorly understood process. To identify molecular components that regulate seed dormancy, we screened T-DNA insertion lines and identified a mutant designated honsu (hon). HON loss-of-function mutants display deep seed dormancy, whereas HON-overexpressing lines display shallow seed dormancy. HON encodes a seed-specific group A phosphatase 2C (PP2C) and is one of the major negative regulators of seed dormancy among group A PP2Cs. Like other PP2C family members, HON interacts with PYR1/RCAR11 in the presence of ABA. Our analysis indicates that HON inhibits ABA signaling and activates gibberellic acid signaling, and both of these conditions must be satisfied to promote the release of seed dormancy. However, HON mRNA levels are increased in mutants displaying deep seed dormancy or under conditions that deepen seed dormancy, and decreased in mutants displaying shallow seed dormancy or under conditions that promote the release of seed dormancy. Taken together, our results indicate that the expression of HON mRNA is homeostatically regulated by seed dormancy. [ABSTRACT FROM PUBLISHER]

This study aimed to examine the effects of bile salts on pharmacokinetics of lovastatin, which has low bioavailability. Lovastatin solid dispersions were prepared using sodium deoxycholate (NaDC) and sodium glycholate (NaGC) at ratios of 1:19, 1:49, and 1:69. The formulated solid dispersions and control (commercial tablet) were administered to rats and plasma concentrations were determined by a validated LC-MS/MS method. Statistically significant differences were found in Cmax, AUC0-10, and AUC0-∞ values among lovastatin formulations ( p < 0.05). NaDC-containing formulations revealed higher bioavailabilities than NaGC-containing solid dispersions at ratios of 1:19 and 1:49. Especially, NaDC-containing formulation at a ratio of 1:19 (NaDC19) showed the highest bioavailability. The AUC (both AUC0-10 and AUC0-∞) of NaDC19 was statistically higher than control and NaDC69 ( p < 0.05). The AUC values decreased as bile salt concentrations increased. Overall, formulations containing bile salts showed higher AUC values than control, even though all formulations did not show significantly higher AUC. In conclusion, the addition of bile salts to lovastatin could enhance drug bioavailabilities. However, too high concentrations of bile salts could decrease bioavailabilities of lovastatin. [ABSTRACT FROM AUTHOR]

Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC50 = 68 pg ml−1, mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic d- and l-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable β-strand-type structure, giving rise to an overall tubular structure over 30 Å in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity. [ABSTRACT FROM AUTHOR]

Severe slugging formation has been investigated experimentally in a two-phase flow-loop composed of a downwardly inclined pipe and a vertical riser. In this study, a bifurcation diagram was made to more clearly identify which flow the current system has at each valve opening. A model was made by inputting the dimensions of the flow loop using OLGA, a multiphase flow simulation program, to compare the experimental results. The model-based control logic was constructed by estimating the transfer function utilizing the OLGA model. The estimated transfer function is used to tune the gain of the PI controller, using the method called the Internal Model Control (IMC). Through this method, PI gain can be easily obtained through only one tuning parameter. When the PI controller gain is obtained through the transfer function of the flow loop system, mitigation of severe slugging was achieved while increasing the flow rate than the case with manual choking. [Display omitted] • This work is about experimental investigation of severe slugging control. • The flow system was linearized using the OLGA model for Internal Model Control. • Gain of the PI controller can be easily obtained using IMC system with OLGA model. • Severe slugging was prevented by controlling the valve opening using IMC system. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzed the sex difference in the effect of smoking exposure on lung cancer in terms of absolute and relative risks despite the increasing lung cancer incidence in Asian female never smokers. Lung cancer risk is positively associated with the duration of smoking, quantity of smoking, and pack-years of smoking, and negatively associated with the number of years since smoking cessation for both sexes. However, higher lung cancer incidence in men than in women with the same level of smoking exposure was observed, suggesting a higher susceptibility for lung cancer in men. Sex should be considered in combination with smoking history in the selection of a lung cancer screening target population. This study analyzed the sex difference in the effect of smoking exposure on lung cancer in terms of absolute and relative risks despite the increasing lung cancer incidence in Asian female never smokers. A retrospective cohort study was conducted on individuals aged 40–79 years who participated in the national health screening program in 2007 and 2008 with linkage to the Korea Central Cancer Registry records. We evaluated sex differences in the age-standardized incidence rate (ASR) of lung cancer by smoking history and the hazard ratio (HR) after adjusting for potential confounders. ASRs for male and female never smokers were 92.5 and 38.3 per 100,000 person-years, respectively (rate ratio (RR) = 2.4; 95% confidence interval (CI) = 2.3–2.5). ASRs for male and female current smokers with a 30 pack-year smoking history were 305.3 and 188.4 per 100,000 person-years, respectively (RR = 1.6; 95% CI = 1.3–2.0). Smoking was significantly associated with lung cancer risk for both sexes. HRs for former smokers versus never smokers were 1.27 (95% CI = 1.23–1.33) for men and 1.43 (95% CI = 1.16–1.81) for women. HRs for current smokers versus never smokers were 2.71 (95% CI = 2.63–2.79) for men and 2.70 (95% CI = 2.48–2.94) for women. HRs for lung cancer increased similarly in both men and women according to smoking status. However, among Korean individuals with comparable smoking statuses, lung cancer incidence is higher in men than in women. Sex should be considered in combination with smoking history in the selection of a lung cancer screening target population. [ABSTRACT FROM AUTHOR]

A correction to the article "Total synthesis of the large non-robosomal peptide polytheonamide B," which was published in the February 21, 2010 issue is presented.