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Abstract: Monolithic arrays of silicon drift detectors (SDDs) have been recently proposed to be used with scintillators for high-position-resolution γ-ray imaging applications. Thanks to the low electronics noise due to the small value of the output capacitance, the SDD offers better noise performances with respect to conventional photodiodes of the same geometry. Small monolithic arrays of SDDs have been used as photodetector of the scintillation light in a first prototype of Anger Camera for γ-ray imaging characterized by an intrinsic resolution better than 0.3mm. In this work, we present a new large-area monolithic array of SDDs. It consists of a single chip composed of 77 single hexagonal units, each one with an active area of 8.7mm2, for a total active area of the device of 6.7cm2. It represents the largest monolithic array of SDDs with on-chip JFETs produced up to now for X-ray and γ-ray detection. The results achieved in the experimental characterization of a first prototype of the detector array are presented, both with X and visible photons. The energy resolution measured at 6keV with the single unit of the array is of 142eV at −10°C, while a QE>90% was measured at λ=550nm. [Copyright &y& Elsevier]

Monolithic arrays of Silicon Drift Detectors (SDDs) have been employed successfully in X-ray spectroscopy and γ-ray imaging applications. Thanks to the low electronics noise achieved at short shaping lime, the SDD is an ideal device for high-resolution and high-rate X-ray spectroscopy experiments at synchrotron sources. Moreover, small monolithic arrays of SDDS have also been used as photodetector of the scintillation light in a first prototype of Anger Camera for γ-ray imaging characterized by an intrinsic resolution better than 0.3 mm. En this work we present a new large- area monolithic array of Silicon Drift Detectors. It consists of a single chip composed by 77 single hexagonal units, each one with a front-end JFET integrated in its center, arranged in a honeycomb configuration. Each SDD unit has an active area of 8.7 mm², for a total active area of the device of 6.7 cm². The linear dimensions of the active area are approximately 29 × 26 mm². It represents the largest monolithic array of SDDs with on-chip JFETs produced up to now for X-ray and γ-ray detection. The results achieved in the experimental characterization of a first prototype of the detector array are presented. They include also the preliminary X-ray spectroscopy characterization of the SDD's units. The energy resolution measured at 6 keV with the single unit of the array is of 142 eV at -10 °C. [ABSTRACT FROM AUTHOR]

DEPFET pixel detectors are unique devices in terms of energy and spatial resolution because very low noise operation can be obtained (ENC = 2.2e- at room temperature) by implementing the amplifying transistor in the pixel cell itself. Full DEPFET pixel matrices have been built and operated for autoradiographical imaging with imaging resolutions of 4.3 ± 0.8 μm at 22 keV. For applications in low energy X-ray astronomy the high energy resolution of DEPFET detectors is attractive. For particle physics, DEPFET pixels are interesting as low mass detectors with high spatial resolution. For a linear collider detector the readout must be very fast. New readout chips have been designed and produced for the development of a DEPFET module for a pixel detector at the proposed TESLA collider, containing 520 × 4000 pixels, with 50 MHz line rate and 25 kHz frame rate. The circuitry contains current memory cells and current hit scanners for fast pedestal subtraction and sparsified readout. The imaging performance of DEPFET devices as well as present achievements toward a DEPFET vertex detector for a linear collider are presented. [ABSTRACT FROM AUTHOR]

In this work, we present a monolithic array of 19 silicon drift detectors (SDDs) used as photodetectors of the scintillation light in position sensitive γ-ray detectors. In this array, having a total sensitive area of about 1 cm2, each SDD has a front-end JFET directly integrated on the detector chip, close to the collecting anode. The low electronic noise offered by each single unit allows to reach a sub-millimeter position resolution by coupling the SDD array to a single CsI(Tl) scintillator crystal in a “mini”-Anger camera scheme. In the paper, a detection module based on the SDD array is described and the noise performances are reported. Moreover, the results in terms of position resolution obtained with the mini Anger Camera realized with the SDD module are presented. [Copyright &y& Elsevier]

The performance requirements of vertex detectors for future linear collider experiments is very challenging especially for the detector''s innermost sensor layers. The DEPleted Field Effect Transistor (DEPFET) combining detector and amplifier operation is capable to meet these requirements. A silicon technology is presented which allows production of large sensor arrays consisting of linear DEPFET detector structures. The envisaged pixel array offers a low noise and low power operation. To ensure a high radiation length a thinning technology based on direct wafer bonding is proposed. [Copyright &y& Elsevier]

Observations in X-ray astronomy require imaging spectroscopy detectors with high-energy resolution, high quantum efficiency, two-dimensional position resolution, large sensitive area, low power consumption, and fast readout. This paper gives a review of the functional principle and performance of fully depleted pn-CCDs and DEPFET based Active Pixel Sensors, both developed at the semiconductor laboratory in Munich, Germany. While pn-CCDs have proved their quality and reliability onboard of the European XMM-Newton satellite in the last 3 years, the Active Pixel Sensor is a promising candidate for the Wide Field Imager of the future XEUS mission. [Copyright &y& Elsevier]

Describes an innovative X-ray fluorescence spectrometer designed to achieve high-energy resolution, position resolution and detection rate in elemental mapping applications. Basis for the identification and localization of chemical elements in an elemental mapping; Reason for employing scanning electron microscopes.

Presents a monolithic array of 19 hexagonal silicon drift detectors (SDD) characterized by a total sensitive area. Composition of the detectors; Impact of having a total sensitive area on each SDD; Nuclear medicine applications that require the development of small compact high-resolution gamma-ray position-sensitive detectors.

Abstract: In this work, we present the results of the experimental characterization of the DRAGO gamma camera. This camera is based on a monolithic array of 77 Silicon Drift Detectors (SDDs), with a total active area of 6.7cm2, coupled to a single CsI(Tl) scintillator crystal, 5mm thick. The use of an array of SDDs provides high quantum efficiency for the detection of the scintillation light together with a very low electronics noise. A very compact detection module based on the use of integrated readout circuits has been developed. Performances achieved in gamma-ray imaging using this camera are here reported. When imaging a 0.2mm collimated 57Co source (122keV) over different points of the active area, a spatial resolution ranging between 0.25 and 0.5mm has been measured. The depth of interaction capability of the detector, thanks to a maximum likelihood reconstruction algorithm here adopted, has been also investigated by imaging a collimated beam tilted to an angle of 45° with respect to the scintillator surface. [Copyright &y& Elsevier]

4D-scanning transmission electron microscopy (4D-STEM) can be used to measure electric fields such as atomic fields or polarization-induced electric fields in crystal heterostructures. The paper focuses on effects occurring in 4D-STEM at interfaces, where two model systems are used: an AlN/GaN nanowire superlattice as well as a GaN/vacuum interface. Two different methods are applied: First, we employ the centre-of mass (COM) technique which uses the average momentum transfer evaluated from the intensity distribution in the diffraction pattern. Second, we measure the shift of the undiffracted disc (disc-detection method) in nano-beam electron diffraction (NBED). Both methods are applied to experimental and simulated 4D-STEM data sets. We find for both techniques distinct variations in the momentum transfer at interfaces between materials: In both model systems, peaks occur at the interfaces and we investigate possible sources and routes of interpretation. In case of the AlN/GaN superlattice, the COM and disc-detection methods are used to measure internal polarization-induced electric fields and we observed a reduction of the measured fields with increasing specimen thickness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Modern quantitative TEM methods such as the ζ-factor technique require precise knowledge of the electron beam current. To this end, a macroscopic Faraday cup was designed and constructed. It can replace the viewing screen in the projection chamber of a TEM and guarantees highly accurate measurement of the electron beam with precision only limited by the used amperemeter. The easy to install, affordable device is shown to be highly apt for precision measurement of currents >5pA. The Faraday cup results are used for an assessment and a comparison of various other beam current measurement methods. It is found that the built-in screen amperemeter of the used TEM is quite inaccurate and that measurements using the screen in general tend to underestimate the current. If present, the drift tube of a spectrometer can also be used as a Faraday cup, but certain described peculiarities have to be taken into account. Direct ultrafast electron detection cameras allow precise measurement at very small currents. For the electron counting technique, which exploits single electron detection capabilities of STEM detectors, a systematic current underestimation was observed and investigated. This results in a reformulated routine for the method and with these improvements it is demonstrated to be capable of accurate high-precision measurements for currents <5pA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Images acquired in transmission electron microscopes can be distorted for various reasons such as e.g. aberrations of the lenses of the imaging system or inaccuracies of the image recording system. This results in inaccuracies of measures obtained from the distorted images. Here we report on measurement and correction of elliptical distortions of diffraction patterns. The effect of this correction on the measurement of crystal lattice strain is investigated. We show that the effect of the distortions is smaller than the precision of the measurement in cases where the strain is obtained from shifts of diffracted discs with respect to their positions in images acquired in an unstrained reference area of the sample. This can be explained by the fact that diffraction patterns acquired in the strain free reference area of the sample are distorted in the same manner as the diffraction patterns acquired in the strained region of interest. In contrast, for samples without a strain free reference region such as nanoparticles or nanoporous structures, where we evaluate ratios of lattice plane distances along different directions, the distortions are usually not negligible. Furthermore, two techniques for the detection of diffraction disc positions are compared showing that for samples in which the crystal orientation changes over the investigated area it is more precise to detect the positions of many diffraction discs simultaneously instead of detecting each disc position independently., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Recent development in fast pixelated detector technology has allowed a two dimensional diffraction pattern to be recorded at every probe position of a two dimensional raster scan in a scanning transmission electron microscope (STEM), forming an information-rich four dimensional (4D) dataset. Electron ptychography has been shown to enable efficient coherent phase imaging of weakly scattering objects from a 4D dataset recorded using a focused electron probe, which is optimised for simultaneous incoherent Z-contrast imaging and spectroscopy in STEM. Therefore coherent phase contrast and incoherent Z-contrast imaging modes can be efficiently combined to provide a good sensitivity of both light and heavy elements at atomic resolution. In this work, we explore the application of electron ptychography for atomic resolution imaging of strongly scattering crystalline specimens, and present experiments on imaging crystalline specimens including samples containing defects, under dynamical channelling conditions using an aberration corrected microscope. A ptychographic reconstruction method called Wigner distribution deconvolution (WDD) was implemented. Experimental results and simulation results suggest that ptychography provides a readily interpretable phase image and great sensitivity for imaging light elements at atomic resolution in relatively thin crystalline materials., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.

Convolutional Neural Networks (CNNs) are an alternative type of neural network that can be used to reduce spectral variations and model spectral correlations which exist in signals. Since speech signals exhibit both of these properties, we hypothesize that CNNs are a more effective model for speech compared to Deep Neural Networks (DNNs). In this paper, we explore applying CNNs to large vocabulary continuous speech recognition (LVCSR) tasks. First, we determine the appropriate architecture to make CNNs effective compared to DNNs for LVCSR tasks. Specifically, we focus on how many convolutional layers are needed, what is an appropriate number of hidden units, what is the best pooling strategy. Second, investigate how to incorporate speaker-adapted features, which cannot directly be modeled by CNNs as they do not obey locality in frequency, into the CNN framework. Third, given the importance of sequence training for speech tasks, we introduce a strategy to use ReLU+dropout during Hessian-free sequence training of CNNs. Experiments on 3 LVCSR tasks indicate that a CNN with the proposed speaker-adapted and ReLU+dropout ideas allow for a 12%-14% relative improvement in WER over a strong DNN system, achieving state-of-the art results in these 3 tasks., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Single shot diffraction imaging experiments via X-ray free-electron lasers can generate as many as hundreds of thousands of diffraction patterns of scattering objects. Recovering the real space contrast of a scattering object from these patterns currently requires a reconstruction process with user guidance in a number of steps, introducing severe bottlenecks in data processing. We present a series of measures that replace user guidance with algorithms that reconstruct contrasts in an unsupervised fashion. We demonstrate the feasibility of automating the reconstruction process by generating hundreds of contrasts obtained from soot particle diffraction experiments.

Characterizing intense, focused x-ray free electron laser (FEL) pulses is crucial for their use in diffractive imaging. We describe how the distribution of average phase tilts and intensities on hard x-ray pulses with peak intensities of 10(21) W/m(2) can be retrieved from an ensemble of diffraction patterns produced by 70 nm-radius polystyrene spheres, in a manner that mimics wavefront sensors. Besides showing that an adaptive geometric correction may be necessary for diffraction data from randomly injected sample sources, our paper demonstrates the possibility of collecting statistics on structured pulses using only the diffraction patterns they generate and highlights the imperative to study its impact on single-particle diffractive imaging.

X-ray free-electron lasers (FELs) enable crystallographic data collection using extremely bright femtosecond pulses from microscopic crystals beyond the limitations of conventional radiation damage. This diffraction-before-destruction approach requires a new crystal for each FEL shot and, since the crystals cannot be rotated during the X-ray pulse, data collection requires averaging over many different crystals and a Monte Carlo integration of the diffraction intensities, making the accurate determination of structure factors challenging. To investigate whether sufficient accuracy can be attained for the measurement of anomalous signal, a large data set was collected from lysozyme microcrystals at the newly established `multi-purpose spectroscopy/imaging instrument' of the SPring-8 Ångstrom Compact Free-Electron Laser (SACLA) at RIKEN Harima. Anomalous difference density maps calculated from these data demonstrate that serial femtosecond crystallography using a free-electron laser is sufficiently accurate to measure even the very weak anomalous signal of naturally occurring S atoms in a protein at a photon energy of 7.3 keV.

Ultrafast laser techniques have revealed extraordinary spin dynamics in magnetic materials that equilibrium descriptions of magnetism cannot explain. Particularly important for future applications is understanding non-equilibrium spin dynamics following laser excitation on the nanoscale, yet the limited spatial resolution of optical laser techniques has impeded such nanoscale studies. Here we present ultrafast diffraction experiments with an X-ray laser that probes the nanoscale spin dynamics following optical laser excitation in the ferrimagnetic alloy GdFeCo, which exhibits macroscopic all-optical switching. Our study reveals that GdFeCo displays nanoscale chemical and magnetic inhomogeneities that affect the spin dynamics. In particular, we observe Gd spin reversal in Gd-rich nanoregions within the first picosecond driven by the non-local transfer of angular momentum from larger adjacent Fe-rich nanoregions. These results suggest that a magnetic material's microstructure can be engineered to control transient laser-excited spins, potentially allowing faster (~ 1 ps) spin reversal than in present technologies.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.

The plasma dynamics of single mesoscopic Xe particles irradiated with intense femtosecond x-ray pulses exceeding 10(16)  W/cm2 from the Linac Coherent Light Source free-electron laser are investigated. Simultaneous recording of diffraction patterns and ion spectra allows eliminating the influence of the laser focal volume intensity and particle size distribution. The data show that for clusters illuminated with intense x-ray pulses, highly charged ionization fragments in a narrow distribution are created and that the nanoplasma recombination is efficiently suppressed.

The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.

We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are essential for developing this novel approach as a useful imaging technique. Applications are 2D reconstructions, orientation classification and finally 3D imaging by assembling 2D patterns into a 3D diffraction volume.

We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.

Protein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo-grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology.

X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.

Diffractive imaging with free-electron lasers allows structure determination from ensembles of weakly scattering identical nanoparticles. The ultra-short, ultra-bright X-ray pulses provide snapshots of the randomly oriented particles frozen in time, and terminate before the onset of structural damage. As signal strength diminishes for small particles, the synthesis of a three-dimensional diffraction volume requires simultaneous involvement of all data. Here we report the first application of a three-dimensional spatial frequency correlation analysis to carry out this synthesis from noisy single-particle femtosecond X-ray diffraction patterns of nearly identical samples in random and unknown orientations, collected at the Linac Coherent Light Source. Our demonstration uses unsupported test particles created via aerosol self-assembly, and composed of two polystyrene spheres of equal diameter. The correlation analysis avoids the need for orientation determination entirely. This method may be applied to the structural determination of biological macromolecules in solution.

X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis 1 . For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information 1-4 . Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology 5 should enable structural determination from submicrometre protein crystals with atomic resolution.

X-ray free-electron lasers deliver intense femtosecond pulses that promise to yield high resolution diffraction data of nanocrystals before the destruction of the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals collected at the Linac Coherent Light Source using 2 keV photons were used for structure determination by molecular replacement and analyzed for radiation damage as a function of pulse length and fluence. Signatures of radiation damage are observed for pulses as short as 70 fs. Parametric scaling used in conventional crystallography does not account for the observed effects.

Single-particle experiments using X-ray Free Electron Lasers produce more than 10(5) snapshots per hour, consisting of an admixture of blank shots (no particle intercepted), and exposures of one or more particles. Experimental data sets also often contain unintentional contamination with different species. We present an unsupervised method able to sort experimental snapshots without recourse to templates, specific noise models, or user-directed learning. The results show 90% agreement with manual classification., (© 2011 Optical Society of America)

X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200 nm to 2 μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

In order to judge differentiation of cells in soft agar colonies, cytological and cytochemical classification of single cells within these colonies is necessary. In this study, 1,026 colonies from 15 normal and 95 leukemic bone marrows have been evaluated using cytological, cytochemical, and immunocytochemical techniques. In 180 colonies from 15 normal controls no segmented neutrophils have been observed. The colonies mostly consisted of monocytes and macrophages, rarely pure eosinophil colonies were observed. The number of monocyte/macrophage colonies in untreated AML and the percentage of pure eosinophil colonies in AML and ALL in remission are reduced, as compared to normal controls. In 174 colonies from a total of 926 colonies derived from bone marrows of leukemic patients, plasma cells and in 20 colonies, blast cells have been observed. In contrast to normal colonies, growth of colonies containing blast cells does not depend upon the conditioned medium of the leukocyte feederlayer. This investigation has demonstrated the necessity of cytological and cytochemical classification in addition to quantiative evaluation of soft agar colonies when studying the effect of factors on proliferation and differentiation of normal and leukemic stem cells.