Synthesis of macrocyclic receptors with intrinsic fluorescence featuring quinizarin moieties

An unprecedented class of macrocycles with intrinsic fluorescence consisting of phenolic trimers and quinizarin is developed. Though they are lacking strong hydrogen bonds as observed in calixarenes, the two examples introduced here each adopt a vase-like conformation with all four aromatic units pointing in one direction (syn orientation). This “cone” conformation has been confirmed by NMR spectroscopy, molecular modeling, and X-ray crystallography. The laminar, electron-rich fluorophore as part of the macrocycle allows additional contacts to enclosed guest molecules

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.New methods for child psychiatric diagnosis and treatment outcome evaluatio

Test simulations of the population dynamics of three <i>imatinib</i>-resistant differentiated cell clones and of the total number of differentiated cells based on model B (Eq (7)) with parameters <i>x</i>_<i>q</i>1(0) = 10.0 and <i>ν</i>_<i>q</i>1 = 0.1.

<p>The panels (a), (b) and (c) correspond to the threshold settings <i>θ</i>_<i>s</i>2 = 10.0, 100.0 and 500.0, respectively. The other parameters employed for the simulations are compiled in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.t002" target="_blank">Table 2</a>. Color scheme: <i>x</i>_<i>d</i>1 (blue), <i>x</i>_<i>d</i>2 (red), <i>x</i>_<i>d</i>3 (green) and <i>y</i> (black). The ordinate unit is number of cells / ml blood.</p

Collection of the coefficients that were employed in the simulations (cf. Sec. 3.4.2) of patient profiles PP14 (Figs 10 and 11) and PP15 (Figs 12–14).

<p>For an explanation of the coefficient symbols see the caption of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.t002" target="_blank">Table 2</a>. This table provides four complete sets of coefficients for a parameterization of Model C. These sets correspond to the simulations presented in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g010" target="_blank">10</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g013" target="_blank">13</a>. The graphs shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g014" target="_blank">Fig 14</a> represent an exception since this figure has been prepared on the basis of a reduced model C, i.e., the equation system has been truncated from a three-clone to a two-clone model by eliminating Subeqs 8e and 8f from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.e021" target="_blank">Eq (8)</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g014" target="_blank">Fig 14</a> consequently does not include graphs for functions <i>x</i>_<i>s</i>3(<i>t</i>) and <i>x</i>_<i>d</i>3(<i>t</i>). Only coefficients related to <i>x</i>_<i>s</i>1(<i>t</i>), <i>x</i>_<i>s</i>2(<i>t</i>), <i>x</i>_<i>d</i>1(<i>t</i>) and <i>x</i>_<i>d</i>2(<i>t</i>) are therefore defined in the column for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g014" target="_blank">Fig 14</a>.</p

Analysis of the solutions of model C (Eq (8)): Overview of the dependence of the formation of a <i>x</i>_<i>d</i>1(<i>t</i>) recurrency on the individual parameters <i>ν</i>_<i>c</i>1, <i>ν</i>_<i>q</i>1, <i>θ</i>_<i>q</i>1, <i>θ</i>_<i>s</i>2 and <i>x</i>_<i>q</i>1(0).

<p>The effects of tuning <i>ν</i>_<i>c</i>1 and <i>θ</i>_<i>s</i>2 on the functions of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.e021" target="_blank">Eq (8)</a> are also documented in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g007" target="_blank">7</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.g009" target="_blank">9</a>.</p

Test simulations of the population dynamics of three <i>imatinib</i>-resistant differentiated cell clones and of the total number of differentiated cells based on model C (Eq (8)) for parameters <i>x</i>_<i>q</i>1(0) = 100.0, <i>ν</i>_<i>q</i>1 = 0.01, <i>θ</i>_<i>q</i>1 = 1.5 × 10⁷ and <i>ν</i>_<i>c</i>1 = 0.1.

<p>The panels (a), (b) and (c) correspond to the threshold settings <i>θ</i>_<i>s</i>2 = 10.0, 100.0 and 500.0, respectively. The other parameters employed for the simulations are compiled in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.t002" target="_blank">Table 2</a>. Color scheme: <i>x</i>_<i>d</i>1 (blue), <i>x</i>_<i>d</i>2 (red), <i>x</i>_<i>d</i>3 (green) and <i>y</i> (black). The ordinate unit is number of cells / ml blood.</p

Fit to PP14 using model C, mutations of stem cells are not taken into account (<i>ν</i>₂ = 0.0, <i>ν</i>₃ = 0.0).

<p>The experimental values for clones Y253H (blue circles), F317L (red squares) and V299L_2 (green diamonds) are considered, clone V299L_1 is ignored by the fit. The evolution of stem and differentiated cell populations is shown in panels (a) and (b), respectively. The teal curve in panel (a) corresponds to the quiescent population of stem cell clone Y253H. In panel (b), the following identifications are made: <i>x</i>_<i>d</i>1(<i>t</i>)(blue curve)↔Y253H, <i>x</i>_<i>d</i>2(<i>t</i>)(red curve)↔F317L, <i>x</i>_<i>d</i>3(<i>t</i>)(green curve)↔V299L_2. The black curve and triangles correspond to the fitted and experimental values of the total leukemic burden, respectively. The ordinate unit of panel (b) refers to the differentiated cell BCR-ABL1 / GUS ratios of the respective clones. While panel (b) reproduces also clinical datasets, the ordinate of panel (a) specifies the size of the stem cell populations in arbitrary units, the scale is determined by the parameters <i>a</i>_<i>i</i>. The parameter set employed for this simulation is compiled in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179700#pone.0179700.t003" target="_blank">Table 3</a>.</p