Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.

Notch1 specifically upregulates expression of the cytokine interferon‐γ in peripheral T cells through activation of NF‐κB. However, how Notch mediates NF‐κB activation remains unclear. Here, we examined the temporal relationship between Notch signaling and NF‐κB induction during T‐cell activation. NF‐κB activation occurs within minutes of T‐cell receptor (TCR) engagement and this activation is sustained for at least 48 h following TCR signaling. We used γ‐secretase inhibitor (GSI) to prevent the cleavage and subsequent activation of Notch family members. We demonstrate that GSI blocked the later, sustained NF‐κB activation, but did not affect the initial activation of NF‐κB. Using biochemical approaches, as well as confocal microscopy, we show that the intracellular domain of Notch1 (N1IC) directly interacts with NF‐κB and competes with IκBα, leading to retention of NF‐κB in the nucleus. Additionally, we show that N1IC can directly regulate IFN‐γ expression through complexes formed on the IFN‐γ promoter. Taken together, these data suggest that there are two ‘waves’ of NF‐κB activation: an initial, Notch‐independent phase, and a later, sustained activation of NF‐κB, which is Notch dependent.

Almost 100% internal quantum efficiency (IQE) is achieved with a green fluorescent organic light-emitting diode (OLED) exhibiting 30% external quantum efficiency (EQE). The OLED comprises an exciplex-forming co-host system doped with a fluorescent dye that has a strong delayed fluorescence as a result of reverse intersystem crossing (RISC); the exciplex-forming co-hosts stimulate energy transfer and charge balance in the system. The orientation of the transition dipole moment of the fluorescent dye is shown to have an influence on the EQE of the device.

Summary T follicular helper (TFH) and Th1 cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these two distinct lineages during viral infection remain unclear. Here, we found that viral-specific TFH and Th1 cells showed reciprocal expression of the transcriptions factors TCF1 and Blimp1 starting early after infection, even before the differential expression of the canonical TFH marker CXCR5. Furthermore, TCF1 was intrinsically required for the TFH-cell response to viral infection; in the absence of TCF1, the TFH-cell response was severely compromised and the remaining TCF1 deficient TFH cells failed to maintain TFH-associated transcriptional and metabolic signatures, which were distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1. Our findings demonstrate an essential role of TCF1 in TFH-cell responses to viral infection.

Blue-phosphorescent organic light-emitting diodes (OLEDs) with 34.1% external quantum efficiency (EQE) and 79.6 lm W(-1) are demonstrated using a hole-transporting layer and electron-transporting layer with low refractive index values. Using optical simulations, it is predicted that outcoupling efficiencies with EQEs > 60% can be achieved if organic layers with a refractive index of 1.5 are used for OLEDs.

The maturation of naive CD8+ T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8+ effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.

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361wileyonlinelibrary.com phosphorescent OLEDs (PhOLEDs) with both high external quantum effi ciency (EQE) and power effi ciency (PE) by tuning the electrical balance, confi ning the excitons in the emitting layer (EML), and reducing the operating voltage of the devices. For example, a large number of host materials with higher triplet (T 1 ) level than that of a blue emitter have been synthesized for a blue EML, and the mixed host systems or dual EMLs have been utilized to achieve good charge balance and exciton confi nement. [24][25][26][27][28][29] New electron or hole transporting materials with high T 1 level adjacent to an EML have also been introduced to confi ne excitons in the EML. [ 5,8,18,[30][31][32][33][34] Moreover, the electrical doping in the injection layers and synthesis of organic materials with high mobility and proper energy level were reported to reduce the operating voltage. [ 14,17,23,31,32,34 ] As a result, the highly effi cient blue PhOLED with a maximum EQE of 30% was reported, [ 22 ] but the device showed large effi ciency rolloff at high luminance and high driving voltage. There are still challenging issues to realize blue PhOLEDs with high EQE, PE, and low effi ciency roll-off at the same time.Use of an exciplex forming co-host is a promising approach to resolve the issues. The effi cient energy transfer from an exciplex forming co-host to phosphorescent dye resulted in high effi ciencies approaching the theoretical limits, low driving voltages, and low effi ciency roll-offs, simultaneously, with a simple structured device. [34][35][36][37][38][39][40] Green, orange and red PhOLEDs and a fl uorescent OLED with EQEs over 30% have been reported, [35][36][37][38][39][40][41][42] but these exciplex forming systems are not applicable to blue dopants because of the higher T 1 level of blue dopants than the T 1 level of exciplexes.The following is required for an exciplex forming co-host for effi cient phosphorescent OLEDs: 1) T 1 level of an exciplex has to be lower than those of the consisting molecules in order to confi ne the excitation energy in the exciplex state, not to be transferred to the consisting molecules, and 2) T 1 level of an exciplex has to be higher than that of a phosphorescent dopant to utilize the energy transfer from the exciplex to a blue dopant. However, seeking for an ideal exciplex system meeting the requirements for a blue dopant seemed to be a challenging issue. [43][44][45] The exciplex forming co-host with phosphorescent dopant system has potential to realize highly effi cient phosphorescent organic light emitting didoes (PhOLEDs). However, the exciplex forming co-host for blue phosphorescent OLEDs has been rarely introduced because of higher triplet level of the blue dopant than green and red dopants. In this work, a novel exciplex forming co-host with high triplet energy level is developed by mixing a phosphine oxide based electron transporting material, PO-T2T, and a hole transporting material, N , N ′-dicarbazolyl-3,5-benzene (mCP). Photo-physical analysi...