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BACKGROUND. Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell–based therapy is a promising modality to treat post-HCT relapse. METHODS. We initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion. RESULTS. In the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires. CONCLUSION. Given their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.

Despite decades of study, the factors that controlled the formation and evolution of the upper reaches of the Yellow River, including uplift of the northeastern Tibetan Plateau, Pliocene- Pleistocene climate change, and autogenetic processes are still poorly constrained. The stratigraphic record of such paleogeographic evolution is recorded in the sequence of nine terraces formed during progressive incision of the Yellow River in the last 1.7 Ma. This article investigates in detail for sediment provenance in terraces of the Lanzhou area, based on heavy-mineral and geochemical (REE) signatures. Two main provenance changes are identified, pointing each to a major paleogeographic reorganization coupled with expansion of the upper Yellow River catchment and enhanced sediment fluxes. The first change took place between the deposition of terrace T9 (formed around 1.7 Ma) and terrace T8 (formed around 1.5 Ma), when rapid fluvial incision point to tectonic control and active uplift of northeastern Tibetan Plateau. The second change took place between deposition of terrace T4 (formed around 0.86 Ma) and terrace T3 (formed around 0.14 Ma), during a period of low incision rates and notably enhanced sediment fluxes as a response to enhanced East Asian Summer Monsoon and consequently increased precipitations, pointing instead chiefly to climatic control.

The upper Yellow River drains the central and northeastern Tibetan Plateau. Understanding the origin of this river is essential for unraveling the interplay between fluvial incision, basement uplift, and climate change. However, the formation age of the upper Yellow River is highly debated, with estimates ranging from Eocene to late Pleistocene. In order to clarify the history of the upper Yellow River, we present a heavy-mineral dataset from drill core in the Yinchuan Basin, a depositional sink at the end of the upper Yellow River course. Our results reveal that the drainage area of the upper Yellow River (i.e., northeastern Tibetan Plateau) has been serving as a major sediment source region for the Yinchuan Basin since at least 3.3 Ma. A late Pleistocene formation of the upper Yellow River, and erosion of neighboring deserts or bounding mountains as an explanation for thick sediment accumulations in this area, is thus ruled out.

The Miocene low-sulphidation epithermal deposits of the Omu camp in northeastern Hokkaido are small past-producers of precious metals and represent significant exploration targets for high-grade Au and Ag ores. The quartz textures of ore samples and the distribution of ore minerals within quartz veins were studied to identify the processes that resulted in the bonanza-grade precious metal enrichment in these deposits. In the high-grade vein samples, which are crustiform or brecciated in hand specimen, ore minerals exclusively occur within colloform quartz bands. High-magnification microscopy reveals that ore-bearing colloform bands consist of fine-grained quartz exhibiting relic microsphere textures and quartz having a mosaic texture that formed through recrystallisation of the microspheres. The presence of relic microspheres is evidence that the microcrystalline quartz hosting the ore minerals formed through recrystallisation of a noncrystalline silica precursor phase. The ore-hosting colloform bands composed of agglomerated microspheres alternate with barren colloform quartz bands that are composed of fibrous chalcedonic quartz and mosaic quartz formed through recrystallisation of the chalcedony. The findings of this study are consistent with previous models linking bonanza-grade precious metal enrichment and the formation of bands of noncrystalline silica in low-sulphidation epithermal veins to episodic vigorous boiling or flashing of the hydrothermal system in the near-surface environment., The Miocene low-sulphidation epithermal deposits of the Omu camp in northeastern Hokkaido are small past-producers of precious metals and represent significant exploration targets for high-grade Au and Ag ores. The quartz textures of ore samples and the distribution of ore minerals within quartz veins were studied to identify the processes that resulted in the bonanza-grade precious metal enrichment in these deposits. In the high-grade vein samples, which are crustiform or brecciated in hand specimen, ore minerals exclusively occur within colloform quartz bands. High-magnification microscopy reveals that ore-bearing colloform bands consist of fine-grained quartz exhibiting relic microsphere textures and quartz having a mosaic texture that formed through recrystallisation of the microspheres. The presence of relic microspheres is evidence that the microcrystalline quartz hosting the ore minerals formed through recrystallisation of a noncrystalline silica precursor phase. The ore-hosting colloform bands composed of agglomerated microspheres alternate with barren colloform quartz bands that are composed of fibrous chalcedonic quartz and mosaic quartz formed through recrystallisation of the chalcedony. The findings of this study are consistent with previous models linking bonanza-grade precious metal enrichment and the formation of bands of noncrystalline silica in low-sulphidation epithermal veins to episodic vigorous boiling or flashing of the hydrothermal system in the near-surface environment.

Spatiotemporal variations in East Asian Monsoon (EAM) precipitation during the Quaternary have been intensively studied. However, spatial variations in pre-Quaternary EAM precipitation remain largely uninvestigated, preventing a clear understanding of monsoon dynamics during a warmer climatic period. Here we compare the spatial differences in heavy mineral assemblages between Quaternary loess and pre-Quaternary Red Clay on the Chinese Loess Plateau (CLP) to analyze spatial patterns in weathering. Prior studies have revealed that unstable hornblende is the dominant (∼50%) heavy mineral in Chinese loess deposited over the past 500 ka, whereas hornblende content decreases to <10% in strata older than ∼1 Ma in the central CLP because of diagenesis. In the present study we found that hornblende is the dominant heavy mineral in 2–2.7 Ma loess on the northeastern CLP (at Jiaxian), which today receives little precipitation. Conversely, hornblende content in the upper Miocene-Pliocene Red Clay at Jiaxian is <10%, as in the central CLP. The early Quaternary abundance of hornblende at Jiaxian indicates that the current northwestward-decreasing precipitation pattern and consequent dry climate at Jiaxian must have been initiated since ∼2.7 Ma, preventing hornblende dissolution to amounts <10% as observed in the central CLP. By contrast, the 7 Ma and 3 Ma Jiaxian Red Clay hornblende content is significantly less than that of the Xifeng samples, despite the fact that today Xifeng receives more precipitation than Jiaxian, with expected enhanced hornblende weathering. This suggests that the northeastern CLP received more precipitation during the Late Miocene-Pliocene than at Xifeng, indicating that the precipitation gradient on the CLP was more east–west during the Late Miocene-Pliocene rather than northwest-southeast as it was in the Quaternary. A comparison of magnetic susceptibility records for these sections confirms this inference. We attribute this major change in cli

Heavy minerals are typically rare but important components of siliciclastic sediments and rocks. Their abundance, proportions, and variability carry valuable information on source rocks, climatic, environmental and transport conditions between source to sink, and diagenetic processes. They are important for practical purposes such as prospecting for mineral resources or the correlation and interpretation of geologic reservoirs. Despite the extensive use of heavy mineral analysis in sedimentary petrography and quite diverse methods for quantifying heavy mineral assemblages, there has never been a systematic comparison of results obtained by different methods and/or operators. This study provides the first interlaboratory test of heavy mineral analysis. Two synthetic heavy mineral samples were prepared with considerably contrasting compositions intended to resemble natural samples. The contributors were requested to provide (i) metadata describing methods, measurement conditions and experience of the operators and (ii) results tables with mineral species and grain counts. One hundred thirty analyses of the two samples were performed by 67 contributors, encompassing both classical microscopic analyses and data obtained by emerging automated techniques based on electron-beam chemical analysis or Raman spectroscopy. Because relatively low numbers of mineral counts (N) are typical for optical analyses while automated techniques allow for high N, the results vary considerably with respect to the Poisson uncertainty of the counting statistics. Therefore standard methods used in evaluation of round robin tests are not feasible. In our case the ‘true’ compositions of the test samples are not known. Three methods have been applied to determine possible reference values: (i) the initially measured weight percentages, (ii) calculation of grain percentages using estimates of grain volumes and densities, and (iii) the best-match average calculated from the most reliable analyses f

Heavy-mineral analysis is a sensitive technique in constraining provenance of sandstone, but has rarely been applied to loess. Here we report a heavy-mineral study of selected samples from the Luochuan, Xifeng and Caoxian loess-Red Clay sections on the Chinese Loess Plateau, based on the novel QEMSCAN (Quantitative Evaluation of Minerals by Scanning Electron Microscopy) technique. We found that heavy mineral assemblages of loess deposited through the past 500. kyr are similar and unchanged by post-depositional chemical dissolution. In contrast, in samples deposited from 900. ka to 3. Ma, the relative proportion of stable minerals tends to increase down section. In addition, the Xifeng samples consistently display higher contents of unstable ferromagnesian minerals than the Luochuan samples. Detailed analysis of surface textures displayed by different minerals by optical methods indicates that such a compositional difference can be ascribed to more effective diagenetic dissolution for the Luochuan section, explained by more extensive percolation of interstitial waters in wetter climatic conditions. Interestingly, heavy-mineral assemblages in the underlying upper Miocene Red Clay from Xifeng (deposition age. ~. 7. Ma) are similar to those of recent loess deposited since 500. ka. This similarity indicates that climate and/or local preservation conditions hampered dissolution reactions, thus helping to preserve an original provenance signal that remained largely unchanged throughout the considered time period. Our study demonstrates that climatically- and time-controlled diagenesis plays a key role in determining the composition of heavy-mineral assemblages contained in loess deposited several hundreds of thousands years ago. We also show that by using both QEMSCAN and traditional optical techniques on the same samples we can obtain fundamental complementary information for a correct interpretation of the heavy-mineral assemblage. © 2013 Elsevier B.V.

Exceptionally large, U-rich apatite from the Schwarzwald ore district (Germany) was triple dated using ID-TIMS U-Pb, fission track (FT) and (U-Th)/He dating methods. The aim of adopting the multi-dating approach on a single sample was to (i) further constrain thermo-tectonic evolution of the Schwarzwald from the formation of crystalline basement through to cooling and exhumation, and (ii) test potential and limitations of in-situ FT-(U-Th)/He double dating.The apatite U-Pb age of 289.5 +/- 4.5 Ma records the cooling of the basement through the 550 degrees C during the Early Permian and brackets the age of the apatite-hosting rhyolite between 289.5 +/- 4.5 Ma and 314 +/- 6 Ma, which is the age of rhyolite-hosting granite. This is in excellent agreement with radiometric ages of related rhyolites and fits with the magmatic evolution of the Schwarzwald during Variscan orogeny. In the Eocene between similar to 50 and 40 Ma, the basement resided at 100 degrees C and then cooled to surface temperatures as revealed by the FT age (37.6 +/- 1.3 Ma) and thermal modelling results based on track lengths.During the cooling event, the basement was likely exhumed as a rift shoulder of newly formed Upper Rhine Graben rift. Nine apatite grains yielded (U-Th)/He ages from 30.7 +/- 1.5 to 65.0 +/- 2.6 Ma (mean age: 45.7 +/- 1.3 Ma). Three possible reasons for the lack of reproducibility are: (i) non-homogeneous distribution of parent isotopes evidenced by strong U zoning, (ii) 'bad neighbourhood causing implantation of extraneous He, and (iii) radiation damage leading to increased He retentivity, implied by the high (>250 ppm) U concentration. These problems could not be circumvented by mechanical abrasion of outermost rim of dated crystals which yielded (U-Th)/He ages from 26.0 +/- 1.0 to 56.2 +/- 2.2 Ma (mean age: 37.2 +/- 1.4 Ma).In-situ FT and traditional (U-Th)/He double dating of single apatite crystals revealed that the vast majority of (U-Th)/He ages were younger than, indis