AbstractInorganic–organic hybrid materials represent a large share of newly reported structures, owing to their simple synthetic routes and customizable properties1. This proliferation has led to a ...characterization bottleneck: many hybrid materials are obligate microcrystals with low symmetry and severe radiation sensitivity, interfering with the standard techniques of single-crystal X-ray diffraction2,3 and electron microdiffraction4–11. Here we demonstrate small-molecule serial femtosecond X-ray crystallography (smSFX) for the determination of material crystal structures from microcrystals. We subjected microcrystalline suspensions to X-ray free-electron laser radiation12,13 and obtained thousands of randomly oriented diffraction patterns. We determined unit cells by aggregating spot-finding results into high-resolution powder diffractograms. After indexing the sparse serial patterns by a graph theory approach14, the resulting datasets can be solved and refined using standard tools for single-crystal diffraction data15–17. We describe the ab initio structure solutions of mithrene (AgSePh)18–20, thiorene (AgSPh) and tethrene (AgTePh), of which the latter two were previously unknown structures. In thiorene, we identify a geometric change in the silver–silver bonding network that is linked to its divergent optoelectronic properties20. We demonstrate that smSFX can be applied as a general technique for structure determination of beam-sensitive microcrystalline materials at near-ambient temperature and pressure.
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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
Mapping the spatial interactions of cancer, immune, and stromal cell states presents novel opportunities for patient stratification and for advancing immunotherapy. While single-cell studies revealed ...significant molecular heterogeneity in prostate cancer cells, the impact of spatial stromal cell heterogeneity remains poorly understood. Here, we used cyclic immunofluorescent imaging on whole-tissue sections to uncover novel spatial associations between cancer and stromal cells in low- and high-grade prostate tumors and tumor-adjacent normal tissues. Our results provide a spatial map of single cells and recurrent cellular neighborhoods in the prostate tumor microenvironment of treatment-naive patients. We report unique populations of mast cells that show distinct spatial associations with M2 macrophages and regulatory T cells. Our results show disease-specific neighborhoods that are primarily driven by androgen receptor-positive (AR+) stromal cells and identify inflammatory gene networks active in AR+ prostate stroma.
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•We provide a detailed spatial map of single cells via cyclic imaging•Distinct mast cell populations are spatially associated with M2 macrophages and Tregs•Grade-specific cellular neighborhoods are identified based on stromal AR expression•Stromal AR expression is correlated with NF-κB1 and HIF1α
Microenvironment; Cancer; Omics
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A multimedia program for computer-assisted psychotherapy has been developed to help patients learn cognitive therapy skills. The program is designed to provide psychoeducation, teach self-help ...methods, and give information to clinicians on the patient's progress in using the software. Multimedia technology is utilized to engage users in the learning process and to make the program accessible for persons who do not have computer or keyboard skills. A preliminary study with 96 subjects who used the software along with treatment as usual found that 75 (78.1%) completed the entire program. Users indicated a high rate of acceptance of this form of computer-assisted therapy, and mean scores on a measure of cognitive therapy knowledge were significantly improved.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
DNA-protein cross-links (DPXs) in fish erythrocytes represent a potential biomarker for exposure to metal cations, such as hexavalent chromium (CrVI) and divalent nickel (NiII). Species-specific ...sensitivities to DPX formation were studied by coexposure of juvenile specimens of rainbow trout, hybrid bluegill, and channel catfish to waterborne metals, such as Cr(VI) and Ni(II). In a species comparison, 4 days of exposure to 2 ppm Cr(VI) induced highest DPXs in bluegill erythrocytes, followed by trout and catfish, at 186%, 97%, and 48% above controls, respectively. A similar pattern of species sensitivity was observed following co-exposure of the fish to 15 ppm Ni(II) for 4 days, with 237%, 124%, and 82% increased DPXs above control bluegill, trout, and catfish, respectively. Biological stability of Cr(VI)-induced DPXs was demonstrated in Cr(VI)-exposed bluegill, as DPX levels remained elevated for up to 20 days after discontinuation of exposure. Similar results were found following exposure of catfish to Ni(II), with detectable DPXs found 10 days after acute exposure. In both bluegill and catfish, a continued increase in DPX formation in erythrocytes was seen for 5-10 days after Cr(VI) was removed from tank water, suggesting that residual Cr(VI) may be involved in DPX formation following acute exposure of fish.
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CEKLJ, 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
Kincaid's lupine (Lupinus sulphureus ssp. kincaidii Smith Phillips), a perennial, leguminous herb of 57 sites in western Oregon and Washington, USA, was recently listed as threatened under the ...federal Endangered Species Act. Results from genetic, pollination, morphological, mating, and distributional studies describe Kincaid's lupine as (a) strongly outcrossing, relying on native insects for most pollination; (b) having large, spreading genets within populations; (c) once widely distributed and abundant, with high levels of interpopulation gene flow; (d) now with isolated populations and a high genetic load that might be causing inbreeding depression; and (e) with high levels of insect prédation on flowers and seeds that contribute to poor reproductive success. Conservation efforts for Kincaid's lupine are often linked with conservation of the closely associated Fender's blue butterfly (Icaricia icarioides fenderi Macy), for which it is the main larval host plant, and have focused on stopping habitat destruction and on managing and restoring habitat. Reducing prairie dominance by tall, herbaceous weeds and woody plants increases Kincaid's lupine vigor. Reestablishment of Kincaid's lupine is possible but requires large numbers of seeds and protection of seedlings from crowding. Further research into the genetics, symbiotic associations, demography, and habitat requirements of Kincaid's lupine is needed for effective recovery of this threatened species. Lupinus sulphureus ssp. kincaidii Smith Phillips, una hierba leguminosa perenne ha sido recientemente listada como amenazada bajo el Acta Federal de Especies Amenazadas en 57 lugares en el Oeste de Oregon y Washington, USA. Los resultados de estudios genéticos, de polinización, morfológicos, de reproducción y de distribución describen a la especie como (a) altamente cruzada, siendo muy importante la actividad de los insectos nativos para la mayoría de su polinización; (b) poseedora de grandes individuos (genets) dentro de las poblaciones; (c) cuando estaba ampliamente distribuida y abundante, con altos niveles de intercambio genético interpoblacional; (d) ahora con poblaciones aisladas y una alta carga génica que podría estar causando depresión por inbreeding; y (e) con altos niveles de predación de insectos en flores y semillas que contribuye al pobre éxito reproductivo. Los esfuerzos de conservación están a menudo relacionados con la conservación de la mariposa azul (Icaricia icarioides fenderi Macy), un asociado cercano, que es el principal huésped larval de la planta, y se ha focalizado en la disminución de la destrucción del hábitat y en el manejo y la restauración del mismo. La reducción de la dominancia de la pradera de plantas herbáceas altas y leñosas, aumentó el vigor de Lupinus sulphureus ssp. kincaidii Smith Phillips. Su reintroducción es posible pero requiere de un gran número de semillas y de la protección de las semillas de la gente. Mayor investigación en genética, asociaciones simbióticas, demografía, y requerimientos de habitat de Lupinus sulphureus ssp. kincaidii Smith Phillips son necesarios para la recuperación efectiva de esta especie amenazada.
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