from the top to the bottom of the electrode area as the liquid fl owed through (Figure 1(vii),(viii) ). The demonstration of EL based on a moving liquid emitter indicates potential for novel device applications, such as microfl uidic devices. However, the fundamental device characteristics of liquid OLEDs are still at a very primitive stage, with low maximum luminance, low EL effi ciency, and high driving voltage. This is because of insufficient carrier injection due to the thickness of the emitting layer and unbalanced carrier recombination based on the simple single-layer structure.Here, we report OLEDs with a liquid emitting layer that exhibit a signifi cantly improved EL effi ciency, maximum luminance and driving voltage compared with previous efforts. [ 7 ] The device architecture of liquid OLEDs was improved by incorporating an electrolyte into the liquid emitting layer and a titanium dioxide (TiO 2 ) layer as a hole-blocking layer. The driving voltage was dramatically decreased by doping a small amount of electrolyte into a liquid emitting layer. Insertion of a TiO 2 hole-blocking layer improved the carrier balance. This architecture resulted in a maximum external EL quantum efficiency ( Φ EL ) of 0.31% ± 0.07% and a maximum luminance of nearly 100 cd/m 2 , which are 10 and 100 times higher, respectively, than those reported previously. [ 7 ] The chemical structures of the compounds used in the liquid emitting layer are shown in Figure 2 a . 9-(2-Ethylhexyl)carbazole (EHCz) was used as the liquid host, while 6-{5-[3-methyl-4-(methyloctyl-amino)-phenyl]-thiophen-2-yl}-naphthalene-2-carboxylic acid hexyl ester (BAPTNCE) and tetrabutylammonium hexafl uorophosphate (TBAHFP) were used as the guest emitter and electrolyte, respectively, and were doped into the EHCz layer. Liquid OLEDs composed of ITO/Poly(3,4-ethylenedioxy thiophene) poly(styrenesulfonate) (PEDOT: PSS) (40 nm)/0.1 wt% TBAHFP, 16.7 wt% BAPTNCE, EHCz (1100 ± 100 nm)/TiO 2 (X nm)/ITO. Spectral characteristics of the host and guest compounds are shown in Figure 2b . The liquid emitting layer composed of 0.1 wt% TBAHFP, 16.7 wt% BAPTNCE, and 83.2 wt% EHCz exhibited green photoluminescence (PL) with a maximum (PL max ) at 511 nm and a PL quantum effi ciency ( Φ F ) of 55%. The absorption spectrum, fl uorescence spectrum, and Φ F of the liquid emitting layer composed of EHCz and BAPTNCE were not changed by doping with 0.1 wt% TBAHFP. This is because energy transfer from EHCz and BAPTNCE to TBAHFP does not occur as TBAHFP does not absorb in the region from 300 to 800 nm. The energy level diagram of the ITO/PEDOT:PSS/0.1 wt% TBAHFP, 16.7 wt% BAPTNCE, EHCz/TiO 2 /ITO device is shown in the inset of Figure 2b .

Background Germline heterozygous mutations in human STAT1 can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases (MSMD), or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis (CMC). LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil and DNA-binding domains (CCD/DBD). Moreover, 6% of CMC patients with a GOF STAT1 mutation develop mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations. Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants Objective Estimate variations in CCD/DBD of STAT1 Method Mutagenized 342 individual wild-type amino acids in CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity. Results Of these 342 mutants, 201 were neutral, 30 LOF, and 111 GOF in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the impact of two hypomorphic and dominant-negative mutations, E157K and G250E, in CCD of STAT1 that we found in two unrelated MSMD patients. Conclusion Systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and impact of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases.

CMCD is a rare congenital disorder characterized by persistent or recurrent skin, nail, and mucosal membrane infections caused by Candida albicans. Heterozygous GOF STAT1 mutations have been shown to confer AD CMCD as a result of impaired dephosphorylation of STAT1. We aimed to identify and characterize STAT1 mutations in CMCD patients and to develop a simple diagnostic assay of CMCD. Genetic analysis of STAT1 was performed in patients and their relatives. The mutations identified were characterized by immunoblot and reporter assay using transient gene expression experiments. Patients' leukocytes are investigated by flow cytometry and immunoblot. Six GOF mutations were identified, three of which are reported for the first time, that affect the CCD and DBD of STAT1 in two sporadic and four multiplex cases in 10 CMCD patients from Japan. Two of the 10 patients presented with clinical symptoms atypical to CMCD, including other fungal and viral infections, and three patients developed bronchiectasis. Immunoblot analyses of patients' leukocytes showed abnormally high levels of pSTAT1 following IFN-γ stimulation. Based on this finding, we performed a flow cytometry-based functional analysis of STAT1 GOF alleles using IFN-γ stimulation and the tyrosine kinase inhibitor, staurosporine. The higher levels of pSTAT1 observed in primary CD14(+) cells from patients compared with control cells persisted and were amplified by the presence of staurosporine. We developed a flow cytometry-based STAT1 functional screening method that would greatly facilitate the diagnosis of CMCD patients with GOF STAT1 mutations.

STAT1-dependent immunity. The other three mutations affect the SH2 domain. The M654K and K673R mutations impair the tyrosine phosphorylation of STAT1, whereas the K637E mutation impairs both STAT1 phosphorylation and GAF-DNA binding. 16,17 These mutations are loss-offunction or hypomorphic and have been shown to exert a dominant-negative effect on wild-type STAT1 for IFN-γ responses.14,15 We report here the molecular and clinical features of a multiplex kindred with MSMD due to a new STAT1 allele, with a mutation of the tyrosine 701 codon. Methods Case reportThe patient (P1) is a 5-year old Japanese boy born to a non-consanguineous family ( Figure 1B). At the age of 2 months he presented with a mild fever and rash. Initial laboratory tests demonstrated leukocytosis (28.9x10 9 /L) with eosinophilia (11.1x10 9

An allosteric host, in which the molecular information of the chiral guest was precisely introduced, exhibits unconventional enantioselectivity toward the target enantiomer even under the conditions of a -20% enantiomeric excess (ee) mixture within a certain concentration window. This is effected by incorporation of the structural information of the enantiomer into the host and the utilization of multiple equilibrium.