The spatiotemporal variations of surface air pollutants (O3, NO2, SO2, CO, and PM10) with four land-use types, residence (R), commerce (C), industry (I) and greenbelt (G), have been investigated at ...283 stations in South Korea during 2002-2013, using routinely observed data. The volatile organic compound (VOC) data at nine photochemical pollutant monitoring stations available since 2007 were utilized in order to examine their effect on the ozone chemistry. The land-use types, set by the Korean government, were generally consistent with the satellite-derived land covers and with the previous result showing anti-correlation between O3 and NO2 in diverse urban areas. The relationship between the two pollutants in the Seoul Metropolitan Area (SMA) residence land-use areas was substantially different from that outside of the SMA, probably due to the local differences in vehicle emissions. The highest concentrations of air pollutants in the diurnal, weekly, and annual cycles were found in industry for SO2 and PMPM10, in commerce for NO2 and CO, and in greenbelt for O3. The concentrations of air pollutants, except for O3, were generally higher in big cities during weekdays, while O3 showed its peak in suburban areas or small cities during weekends. The weekly cycle and trends of O3 were significantly out of phase with those of NO2, particularly in the residential and commercial areas, suggesting that vehicle emission was a major source in those areas. The ratios of VOCs to NO2 for each of the land-use types were in the order of I (10.2) > C (8.7) > G (3.9) > R (3.6), suggesting that most areas in South Korea were likely to be VOC-limited for ozone chemistry. The pollutants (NO2, SO2, CO, and PMPM10 except for O3 have decreased, most likely due to the effective government control. The total oxidant values (OX = O3 + NO2) with the land-use types were analyzed for the local and regional (or background) contributions of O3, respectively, and the order of OX (ppb) was C (57.4) > R (53.6) > I (50.7) > G (45.4), indicating the greenbelt observation was close to the background.
We discuss the photoluminescence (PL) of semiconducting transition metal dichalcogenides on the basis of experiments and a microscopic theory. The latter connects ab initio calculations of the ...single-particle states and Coulomb matrix elements with a many-body description of optical emission spectra. For monolayer MoS2, we study the PL efficiency at the excitonic A and B transitions in terms of carrier populations in the band structure and provide a quantitative comparison to an (In)GaAs quantum well-structure. Suppression and enhancement of PL under biaxial strain is quantified in terms of changes in the local extrema of the conduction and valence bands. The large exciton binding energy in MoS2 enables two distinctly different excitation methods: above-band gap excitation and quasi-resonant excitation of excitonic resonances below the single-particle band gap. The latter case creates a nonequilibrium distribution of carriers predominantly in the K-valleys, which leads to strong emission from the A-exciton transition and a visible B-peak even if the band gap is indirect. For above-band gap excitation, we predict a strongly reduced emission intensity at comparable carrier densities and the absence of B-exciton emission. The results agree well with PL measurements performed on monolayer MoS2 at excitation wavelengths of 405 nm (above) and 532 nm (below the band gap).
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IJS, KILJ, NUK, PNG, UL, UM
Regulatory T (Treg) cells, whose identity and function are defined by the transcription factor Foxp3, are indispensable for immune homeostasis. It is unclear whether Foxp3 exerts its Treg lineage ...specification function through active modification of the chromatin landscape and establishment of new enhancers or by exploiting a pre-existing enhancer landscape. Analysis of the chromatin accessibility of Foxp3-bound enhancers in Treg and Foxp3-negative T cells showed that Foxp3 was bound overwhelmingly to preaccessible enhancers occupied by its cofactors in precursor cells or a structurally related predecessor. Furthermore, the bulk of Foxp3-bound Treg cell enhancers lacking in Foxp3− CD4+ cells became accessible upon T cell receptor activation prior to Foxp3 expression, and only a small subset associated with several functionally important genes were exclusively Treg cell specific. Thus, in a late cellular differentiation process, Foxp3 defines Treg cell functionality in an “opportunistic” manner by largely exploiting the preformed enhancer network instead of establishing a new enhancer landscape.
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► Treg cell specification factor Foxp3 binds to preaccessible enhancer ► Foxp3 binds to sites occupied by cofactors in precursor cell ► Structural homolog Foxo1 serves as a Foxp3 predecessor in precursor cells ► TCR activation confers accessibility to the majority of Treg-specific enhancers
The transcription factor Foxp3, which specifies regulatory T cell fate, promotes differentiation not by making chromatin more accessible to specific factors but instead by modifying transcriptional activity at pre-existing enhancers, which are already accessible due to the binding of cofactors and paralogs in precursor cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A comprehensive catalog of 623 galactic eclipsing binary (EB) systems with eccentric orbits is presented with more than 2830 times of minima determined from the archived photometric data by various ...sky-survey projects and new photometric measurements. The systems are divided into two groups according to whether the individual system has a GCVS name or not. All the systems in both groups are further classified into three categories (D, A, and A+III) on the basis of their eclipse timing diagrams: 453 D systems showing just constantly displaced secondary minima, 139 A systems displaying only apsidal motion (AM), and 31 A+III systems exhibiting both AM and light-time effects. AM parameters for 170 systems (A and A+III systems) are consistently calculated and cataloged with basic information for all systems. Some important statistics for the AM parameters are discussed and compared with those derived for the eccentric EB systems in the Large and Small Magellanic Clouds.
A novel concept for integrating visible light communications (VLC) with three‐dimensional indoor positioning is presented. A VLC link based on transmitter and receiver characteristics using ...experimental measurements was modelled. Proposed is a three‐dimensional positioning algorithm using received signal strength indication, which changes based on the angle and distance of the location based service. To reduce inter‐cell interference, the transmitter's location code was sent using different subcarriers. A demonstration shows that the proposed algorithm can obtain a user's position, including height, accurately and without inter‐cell interference.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking ...antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics. Using genetic deletion in preclinical mouse models, here we show that PD-L1 from disparate cellular sources, including tumour cells, myeloid or other immune cells can similarly modulate the degree of cytotoxic T-cell function and activity in the tumour microenvironment. PD-L1 expression in both the host and tumour compartment contribute to immune suppression in a non-redundant fashion, suggesting that both sources could be predictive of sensitivity to therapeutic agents targeting the PD-L1/PD-1 axis.
Programmed cell death–1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to ...suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1–recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti–PD-L1/PD-1 therapy.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Abstract To investigate the effect of the sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 on bone regeneration in rat calvarial defects (40 Sprague-Dawley rats, 8 mm defect size), ...all animals were treated with a hydroxyapatite (HA)/tricalcium phosphate (TCP) bone graft covered with a collagen membrane. The experimental groups were as follows: (1) control group: unmodified collagen (no treatment); (2) BMP-2 group: 5 μg of BMP-2; (3) hep-BMP-7 group: 5 μg BMP-7 chemically bound to heparinized collagen; and (4) BMP-2/hep-BMP-7 group: 2.5 μg BMP-7 bound to heparinized collagen and subsequently treated with 2.5 μg BMP-2. Defect healing was examined at 2 and 8 weeks after surgery. The BMP-2 group showed the largest new bone area at week 2 (29.3 ± 7.3%; P = 0.009); new bone areas in the hep-BMP-7 and BMP-2/hep-BMP-7 groups were similar (11.8 ± 3.4% and 12.9 ± 5.71%, respectively; P = 0.917). After 8 weeks, the BMP-2/hep-BMP-7 group showed the largest new bone area (43.3 ± 6.2%), followed by the BMP-2 and hep-BMP-7 groups ( P = 0.013). Accordingly, in comparison with single deliveries of BMP-2 and BMP-7, sequential delivery of BMP-2 and BMP-7 using a heparinized collagen membrane significantly induced new bone formation with a smaller quantity of BMP-2 in rat calvarial defects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) can induce regression of tumors bearing activating mutations in the Ras pathway but rarely leads to tumor eradication. ...Although combining MEK inhibition with T-cell-directed immunotherapy might lead to more durable efficacy, T cell responses are themselves at least partially dependent on MEK activity. We show here that MEK inhibition did profoundly block naive CD8+ T cell priming in tumor-bearing mice, but actually increased the number of effector-phenotype antigen-specific CD8+ T cells within the tumor. MEK inhibition protected tumor-infiltrating CD8+ T cells from death driven by chronic TCR stimulation while sparing cytotoxic activity. Combining MEK inhibition with anti-programmed death-ligand 1 (PD-L1) resulted in synergistic and durable tumor regression even where either agent alone was only modestly effective. Thus, despite the central importance of the MAP kinase pathway in some aspects of T cell function, MEK-targeted agents can be compatible with T-cell-dependent immunotherapy.
•Pharmacologic inhibition of MEK potentiates rather than hinders anti-tumor T cells•MEK inhibitors nonetheless suppress anti-tumor priming in lymph nodes in vivo•MEK inhibitors potentiate anti-tumor T cells by impairing TCR-driven apoptosis•MEK inhibition combines with anti-PD-L1 treatment to yield durable tumor regression
MEK is a critical signaling component for both Ras-pathway-mutated tumors and normal T cells. Mellman and colleagues demonstrate that MEK inhibitors potentiate rather than suppress T-cell-based anti-tumor immunity and can combine successfully with anti-PD-L1 immunotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mice lacking the transcription factor Foxp3 (Foxp3(-)) lack regulatory T (T(reg)) cells and develop fatal autoimmune pathology. In Foxp3(-) mice, many activated effector T cells express self-reactive ...T cell receptors that are expressed in T(reg) cells in wild-type mice. Thus, in wild-type mice, most self-reactive thymocytes escaping negative selection are diverted into the T(reg) lineage, and whether T(reg) cells are critical in self-tolerance in wild-type mice remains unknown. Here, acute in vivo ablation of T(reg) cells demonstrated a vital function for T(reg) cells in neonatal and adult mice. We suggest that self-reactive T cells are continuously suppressed by T(reg) cells and that when suppression is relieved, self-reactive T cells become activated and facilitate accelerated maturation of dendritic cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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