The slow maturation time of fluorescent proteins (FPs) limits the temporal accuracy of measurements of rapid processes such as gene expression dynamics and effectively reduces fluorescence signal in ...growing cells. We used high-precision time-lapse microscopy to characterize the maturation kinetics of 50 FPs that span the visible spectrum at two different temperatures in Escherichia coli cells. We identified fast-maturing FPs from this set that yielded the highest signal-to-noise ratio and temporal resolution in individual growing cells.
Viologens are one of the most well-known electrochromic (EC) chromophores. In particular, symmetric dialkyl viologens have been widely used in EC devices (ECDs), but suffer from the formation of ...viologen radical cation dimers that deteriorate device performance. In this work, we propose an effective route to suppress dimer formation through molecularly altering one of the N-substituents. We prepare 1-benzyl-1′-heptyl viologens and find that such asymmetric molecular structures attribute to the suppression of dimer production when used as EC chromophores. The suppression of dimer formation allows us to drive the device at relatively higher voltages, so that we could achieve viologen-based ECDs showing large transmittance changes between colored and bleached states, efficient and fast coloration, and stable coloration/bleaching cyclic operation. The results indicate that high-performance ECDs can be realized by utilizing viologens containing asymmetric molecular structures.
Asymmetric viologens are proposed for highly stable electrochromic devices.
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IJS, KILJ, NUK, UL, UM, UPUK
The objective of this study was to compare the outcomes of parent artery occlusion (PAO) versus stent‐assisted reconstruction in radiated nasopharyngeal carcinoma (NPC) patients with internal carotid ...artery (ICA) blowouts. A retrospective review from our institution (2011–2021) and systematic review of Pubmed and Embase (1995–2022) was performed. Twenty‐eight eligible studies were identified. Eighty‐six PAOs and 37 stent‐assisted reconstructions were analyzed, including 11 PAOs and 5 stents from our institution. Stents were associated with significantly higher incidence of overall re‐bleeding (16.2% 95% CI 7.4–31.9 vs. 4.6% 95% CI 1.3–13.5, p = 0.047), delayed stroke (5.4% 95% CI 1.3–19.4 vs. 0%, p = 0.034) and reduced median survival (7.1 95% CI 3.8–14.0 months vs. 29.0 95% CI 9.4–63.4 months, p = 0.017) compared to PAO. There were no significant differences in terms of overall stroke, infection, extruded/migrated foreign body, and peri‐procedure death. PAO is preferred over reconstructive treatment in patients with adequate collateral circulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Stochastic pulsatile dynamics have been observed in an increasing number of biological circuits with known mechanism involving feedback control and bistability. Surprisingly, recent single-cell ...experiments in Escherichia coli flagellar synthesis showed that flagellar genes are activated in stochastic pulses without the means of feedback. However, the mechanism for pulse generation in these feedbackless circuits has remained unclear. Here, by developing a system-level stochastic model constrained by a large set of single-cell E. coli flagellar synthesis data from different strains and mutants, we identify the general underlying design principles for generating stochastic transcriptional pulses without feedback. Our study shows that an inhibitor (YdiV) of the transcription factor (FlhDC) creates a monotonic ultrasensitive switch that serves as a digital filter to eliminate small-amplitude FlhDC fluctuations. Furthermore, we find that the high-frequency (fast) fluctuations of FlhDC are filtered out by integration over a timescale longer than the timescale of the input fluctuations. Together, our results reveal a filter-and-integrate design for generating stochastic pulses without feedback. This filter-and-integrate mechanism enables a general strategy for cells to avoid premature activation of the expensive downstream gene expression by filtering input fluctuations in both intensity and time so that the system only responds to input signals that are both strong and persistent.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
ABSTRACT
Prior studies find that delayed earnings announcements tend to communicate unfavorable news, and investors react negatively when firms delay earnings announcements. However, these findings ...do not explain why investors discount delayed earnings, even after controlling for the earnings news, and why firms sometimes announce good news late. Motivated by theory from Trueman (1990) that attempts to explain these phenomena, we examine whether announcement delays indicate earnings management. We predict and find that good news firms with higher discretionary accruals are more likely to announce earnings late. Consistent with post fiscal year‐end activities driving announcement delays, we fail to find a relation between measures of real earnings management and late announcements. Using a last‐chance earnings management measure based on tax expense manipulation, we also predict and find strong evidence that good news firms engaging in last‐chance earnings management are more likely to delay earnings announcements. Consistent with Trueman's (1990) theory that earnings management explains why investors discount delayed earnings announcements, we find that, on average, earnings announcement returns are 1.4% lower for late announcers relying on last‐chance earnings management to report good news. Overall, our findings suggest that announcement delays provide information about not only the sign of the earnings news but also the potential for earnings management.
RÉSUMÉ
Pourquoi les entreprises communiquent les bonnes nouvelles tardivement : gestion des résultats et ponctualité de la communication d'information financière
Selon des études antérieures, les annonces de résultats tardives font souvent état de nouvelles défavorables, et les investisseurs réagissent négativement lorsque les entreprises retardent ces annonces. Toutefois, ces constats n'expliquent pas pour quelles raisons les investisseurs écartent les annonces tardives, même après avoir vérifié la teneur de l'information qu'on y retrouve, ni pourquoi les entreprises communiquent parfois des bonnes nouvelles de façon tardive. Faisant écho à la théorie de Trueman (1990) qui tente d'expliquer ces phénomènes, nous vérifions si le fait de retarder ces annonces est révélateur d'une manipulation des résultats. Nous prédisons et montrons que les entreprises qui communiquent de bonnes nouvelles et ont eu recours à d'importantes régularisations discrétionnaires sont plus susceptibles de communiquer leurs résultats tardivement. Étant donné que les activités suivant la fin de l'exercice entraînent des retards sur le plan des annonces, nous n'avons pas pu établir une relation entre les indicateurs de gestion des résultats réels et les annonces tardives. Au moyen d'un indicateur de la gestion de dernière minute des résultats fondée sur la manipulation des charges fiscales, nous prédisons et mettons au jour de solides données probantes indiquant que les entreprises qui ont recours à ce type de gestion et communiquent de bonnes nouvelles sont plus susceptibles de retarder l'annonce des résultats. Conformément à la théorie de Trueman (1990) selon laquelle la gestion des résultats est la raison pour laquelle les investisseurs écartent les annonces de résultats tardives, nous montrons qu'en moyenne, les retours sur les annonces de résultats sont inférieurs de 1,4% pour les entreprises dont les annonces sont tardives et qui s'appuient sur la gestion de dernière minute des résultats pour présenter des nouvelles positives. Dans l'ensemble, nos résultats portent à croire que les retards touchant les annonces fournissent de l'information non seulement sur la teneur de l'information divulguée, mais également sur la possibilité de manipulation des résultats.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The classic picture of flagellum biosynthesis in
, inferred from population measurements, depicts a deterministic program where promoters are sequentially up-regulated and are maintained steadily ...active throughout exponential growth. However, complex regulatory dynamics at the single-cell level can be masked by bulk measurements. Here, we discover that in individual
cells, flagellar promoters are stochastically activated in pulses. These pulses are coordinated within specific classes of promoters and comprise "on" and "off" states, each of which can span multiple generations. We demonstrate that in this pulsing program, the regulatory logic of flagellar assembly dictates which promoters skip pulses. Surprisingly, pulses do not require specific transcriptional or translational regulation of the flagellar master regulator, FlhDC, but instead appears to be essentially governed by an autonomous posttranslational circuit. Our results suggest that even topologically simple transcriptional networks can generate unexpectedly rich temporal dynamics and phenotypic heterogeneities.
Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to ...elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell lines, and orthotopic mouse models. We demonstrated a previously unrecognized mechanism whereby nuclear PXN enhances angiogenesis by transcriptionally regulating SRC expression. SRC, in turn, increases PLAT expression through NF-ĸB activation; PLAT promotes angiogenesis via LRP1 in endothelial cells. PXN silencing in ovarian cancer mouse models reduced angiogenesis, tumor growth, and metastasis. These findings provide a new understanding of the role of PXN in regulating tumor angiogenesis and growth.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A 14-y-old, castrated male, diabetic, domestic longhaired cat was presented for investigation of anemia. General examination revealed widespread cutaneous erythematous macules and patches. Hematology ...and bone marrow aspiration revealed severe regenerative anemia and marked erythroid hyperplasia, respectively. Low numbers of intermediate-to-large, atypical lymphocytes were observed in the blood smear and bone marrow aspirates. Various imaging modalities demonstrated a diffuse pulmonary bronchial pattern, multifocal mural thickening of the urinary bladder, splenomegaly, and mild tri-cavitary effusion. Skin biopsies and cytologic examination of the pleural effusion demonstrated round-cell neoplasia consistent with lymphoma. Autopsy confirmed disseminated T-cell lymphoma, mostly affecting the urinary bladder, stomach, lymph nodes, and interscapular subcutis and muscles. Angiocentrism and nerve infiltration were present. The cutaneous erythematous patches, characterized by perivascular neoplastic lymphocytic infiltrates and angiodestruction, were a manifestation of the disseminated lymphoma in this cat, similar to the lesions reported in humans affected by angioimmunoblastic T-cell lymphoma.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We present ADIOS 2, the latest version of the Adaptable Input Output (I/O) System. ADIOS 2 addresses scientific data management needs ranging from scalable I/O in supercomputers, to data analysis in ...personal computer and cloud systems. Version 2 introduces a unified application programming interface (API) that enables seamless data movement through files, wide-area-networks, and direct memory access, as well as high-level APIs for data analysis. The internal architecture provides a set of reusable and extendable components for managing data presentation and transport mechanisms for new applications. ADIOS 2 bindings are available in C++11, C, Fortran, Python, and Matlab and are currently used across different scientific communities. ADIOS 2 provides a communal framework to tackle data management challenges as we approach the exascale era of supercomputing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Actinic keratosis therapy can elicit unsightly and painful local skin responses; assessment of treatment satisfaction and health-related quality of life (QoL) is important. Ingenol ...mebutate gel is a novel topical field therapy for actinic keratosis. Objective Post-hoc analyses were performed based on patient-reported outcomes from phase-III trials (n = 1005) to assess the effects of ingenol mebutate on QoL and the relationship between both QoL and treatment satisfaction, and degree of lesion clearance. Methods Patients received ingenol mebutate or vehicle for self-application to a 25-cm2 contiguous area: 0.015% once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2 consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction Questionnaire for Medication data were recorded. Results Significant, positive associations between Treatment Satisfaction Questionnaire for Medication score and degree of clearance were identified for patients in the face/scalp (effectiveness P < .0001 and global satisfaction P = .0002) and trunk/extremities ( P < .0001 and P = .0014, respectively) groups. There was a significant association between Skindex-16 score and clearance for patients in the face/scalp group for change in symptoms ( P = .0218), emotions ( P = .0002), and overall Skindex-16 score ( P = .0006) from baseline. Limitations Clinical trial population findings may not be generalizable to clinical practice. Conclusion Ingenol mebutate significantly improved patients' QoL and treatment satisfaction. Improvements were associated with higher degrees of actinic keratosis lesion clearance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK