Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform efforts to generate human kidney structures and comparative functional analyses across mammalian species.

Real-time vibrational spectroscopic imaging is desired for monitoring cellular states and cellular processes in a label-free manner. Raman spectroscopic imaging of highly dynamic systems is inhibited by relatively slow spectral acquisition on millisecond to second scale. Here, we report microsecond scale vibrational spectroscopic imaging by lock-in free parallel detection of spectrally dispersed stimulated Raman scattering signal. Using a homebuilt tuned amplifier array, our method enables Raman spectral acquisition, within the window defined by the broadband pulse, at the speed of 32 microseconds and with close to shot-noise limited detection sensitivity. Incorporated with multivariate curve resolution analysis, our platform allows compositional mapping of lipid droplets in single live cells, observation of intracellular retinoid metabolism, discrimination of fat droplets from protein-rich organelles in Caenorhabditis elegans, spectral detection of fast flowing tumor cells, and monitoring drug diffusion through skin tissue in vivo. The reported technique opens new opportunities for compositional analysis of cellular compartment in a microscope setting and high-throughput spectral profiling of single cells in a flow cytometer setting.

Flow cytometry is one of the most important technologies for high-throughput single-cell analysis. Fluorescent labeling acts as the primary approach for cellular analysis in flow cytometry. Nevertheless, the fluorescent tags are not applicable to all cases, especially to small molecules, for which labeling may significantly perturb the biological functionality. Spontaneous Raman scattering flow cytometry offers the capability to non-invasively detect chemical contents of cells but suffers from slow data acquisition. In order to achieve label-free high-throughput single-particle analysis using Raman scattering, we developed a 32-channel multiplex stimulated Raman scattering flow cytometry (SRS-FC) technique that can measure chemical contents of single particles at a speed of 5 μs per Raman spectrum. Using mixed polymer beads, we demonstrate the discrimination of different particles at a throughput of up to 11,000 particles per second. This is a four orders of magnitude improvement in throughput compared to conventional spontaneous Raman flow cytometry. As a proof of concept, we show the differentiation of 3T3-L1 cells at different states by SRS-FC according to the difference in cellular chemical content. The SRS-FC technique opens new opportunities for high-throughput and high-content chemical analysis of live cells in a label-free manner.

We report experiments on the impact of 2.5 MeV proton irradiation on self-diffusion and dopant diffusion in germanium (Ge). Self-diffusion under irradiation reveals an unusual depth independent broadening of the Ge isotope multilayer structure. This behavior and the observed enhanced diffusion of B and retarded diffusion of P demonstrates that an interstitial-mediated diffusion process dominates in Ge under irradiation. This fundamental finding opens up unique ways to suppress vacancy-mediated diffusion in Ge and to solve the donor deactivation problem that hinders the fabrication of Ge-based nanoelectronic devices. DOI: 10.1103/PhysRevLett.103.255501 PACS numbers: 61.80.Jh, 61.72.jj, 61.82.Fk, 81.40.Wx Over the past few years the elemental semiconductor Ge has been the subject of many experimental [1-13] and theoretical investigations [14][15][16][17][18][19][20][21][22][23][24][25] to elucidate the electronic and diffusion properties of point defects as well as their interaction. Understanding these properties helps to develop strategies for efficient defect engineering that are crucial for the fabrication of the next generation of nanoelectronic devices. Utilizing Ge instead of silicon (Si) for complementary metal oxide semiconductors (CMOS) technology one can take advantage of the higher electron and hole mobilities in Ge compared to Si [26]. Whereas the p-channel Ge-MOSFET (metal oxide semiconductor fieldeffect transistor) made of heavily B doped source and drain regions was already demonstrated [27], the n-channel MOSFET remains a challenge due to the enhanced diffusion of n-type dopants such as P, As, and Sb under extrinsic doping conditions and the deactivation of the donors for concentrations exceeding 10 19 cm À3 [7,9,27]. The enhanced diffusion is a consequence of the singly negatively charged donor-vacancy ðAVÞ À pair that mediates donor diffusion in Ge according to the reaction [7,9] where A þ s and V 2À are the singly positively charged substitutional donor with A 2 fP; As; Sbg and the doubly negatively charged vacancy (V 2À ), respectively. The deactivation is related to the formation of inactive donorvacancy clusters whose formation is favored due to Coulomb attraction between A þ s and ðAVÞ À via the reaction [9]The formation of A 2 V and even bigger clusters A n V m is consistent with the predictions of density functional theory calculations [23]. Reactions (1) and (2) indicate that the donor-vacancy pair mediates both the diffusion and deactivation of n-type dopants in Ge. Effective defect engineering that aims to suppress the enhanced diffusion and deactivation of donors in Ge should reduce the concentration of the AV pairs. In this letter we demonstrate that defect engineering with Ge interstitials makes it possible to effectively suppress the enhanced diffusion of donor atoms.

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