Three-Dimensional Crystallographic Reconstruction for Atomic Resolution

Three-dimensional structures have recently been determined by electron crystallography at a resolution high enough to determine atomic arrangements in both protein and mineral specimens. The different nature of these two types of specimens produces some very significant differences in the way data is obtained and processed, although the principles are the same. The sensitivity of proteins to damage by the electron beam limits the signal-to-noise ratio in the image and the resolution to which data can be extracted from the image. A number of constraints, such as the amino acid sequence and the connectivity of atoms within amino acids, can be used in interpreting the limited image data. In materials samples, the relative insensitivity to damage allows obtaining resolution limited only by the microscope. In many samples, dynamical scattering and other non-linear effects limit the information in the image, but this limit can be circumvented by working in very thin areas of the specimen

Cognitive therapy and spirituality: the battleground and the blend

Includes bibliographical references

Improving Palliative Care with Deep Learning

Improving the quality of end-of-life care for hospitalized patients is a priority for healthcare organizations. Studies have shown that physicians tend to over-estimate prognoses, which in combination with treatment inertia results in a mismatch between patients wishes and actual care at the end of life. We describe a method to address this problem using Deep Learning and Electronic Health Record (EHR) data, which is currently being piloted, with Institutional Review Board approval, at an academic medical center. The EHR data of admitted patients are automatically evaluated by an algorithm, which brings patients who are likely to benefit from palliative care services to the attention of the Palliative Care team. The algorithm is a Deep Neural Network trained on the EHR data from previous years, to predict all-cause 3-12 month mortality of patients as a proxy for patients that could benefit from palliative care. Our predictions enable the Palliative Care team to take a proactive approach in reaching out to such patients, rather than relying on referrals from treating physicians, or conduct time consuming chart reviews of all patients. We also present a novel interpretation technique which we use to provide explanations of the model's predictions.Comment: IEEE International Conference on Bioinformatics and Biomedicine 201

A CCD Camera with Electron Decelerator for Intermediate Voltage Electron Microscopy

Electron microscopists are increasingly turning to Intermediate Voltage Electron Microscopes (IVEMs) operating at 300 - 400 kV for a wide range of studies. They are also increasingly taking advantage of slow-scan charge coupled device (CCD) cameras, which have become widely used on electron microscopes. Under some conditions CCDs provide an improvement in data quality over photographic film, as well as the many advantages of direct digital readout. However, CCD performance is seriously degraded on IVEMs compared to the more conventional 100 kV microscopes. In order to increase the efficiency and quality of data recording on IVEMs, we have developed a CCD camera system in which the electrons are decelerated to below 100 kV before impacting the camera, resulting in greatly improved performance in both signal quality and resolution compared to other CCDs used in electron microscopy. These improvements will allow high-quality image and diffraction data to be collected directly with the CCD, enabling improvements in data collection for applications including high-resolution electron crystallography, single-particle reconstruction of protein structures, tomographic studies of cell ultrastructure and remote microscope operation. This approach will enable us to use even larger format CCD chips that are being developed with smaller pixels

USAF single-event sonic boom prediction model: PCBoom3

The Air Force has developed PCBoom3, a general-purpose, single-event sonic boom prediction model. The model operates on an IBM PC or compatible, under DOS or Windows. It is accessed via an integrated environment which controls building of input cases, running boom calculations, displaying contours and signatures, and managing all associated data. The primary boom calculation is via a variation of FOBOOM, the focus-boom extension of Thomas's program. Aircraft input is either via a user-provided F-function, or simple N-wave F-functions tabulated for about 20 current aircraft. A fast boom calculation, based on Plotkin's SBORT algorithms, is included for simple N-wave F-functions in a windless atmosphere and flight altitudes up to 60,000 feet. After a run is complete, the user can access an index identifying significant events (focal zones, beginning of footprint, etc.), then plot boom amplitude contours and signatures or spectra at any point in the footprint. The primary uses of this program are expected to be operational planning and boom incident investigation. However, because of the commonality between FOBOOM and the MDBOOM program currently being used for low boom configuration design, this program is of interest to the HSCT community, especially as supersonic route planning activity increases. The Air Force recently conducted a flight test program to evaluate the focal zone capabilities of PCBoom3. Initial results of that program validate the prediction of focal zone geometry, amplitudes, and waveforms

Structural insights into microtubule doublet interactions inaxonemes

Coordinated sliding of microtubule doublets, driven by dynein motors, produces periodic beating of the axoneme. Recent structural studies of the axoneme have used cryo-electron tomography to reveal new details of the interactions among some of the multitude of proteins that form the axoneme and regulate its movement. Connections among the several sets of dyneins, in particular, suggest ways in which their actions may be coordinated. Study of the molecular architecture of isolated doublets has provided a structural basis for understanding the doublet's mechanical properties that are related to the bending of the axoneme, and has also offered insight into its potential role in the mechanism of dynein activity regulation

Restoration of Weak Phase-Contrast Images Recorded With a High Degree of Defocus: The "Twin Image" Problem Associated With CTF Correction

Relatively large values of objective-lens defocus must normally be used to produce detectable levels of image contrast for unstained biological specimens, which are generally weak phase objects. As a result, a subsequent restoration operation must be used to correct for oscillations in the contrast transfer function (CTF) at higher resolution. Currently used methods of CTF-correction assume the ideal case in which Friedel mates in the scattered wave have contributed pairs of Fourier components that overlap with one another in the image plane. This"ideal" situation may be only poorly satisfied, or not satisfied at all, as the particle size gets smaller, the defocus value gets larger, and the resolution gets higher. We have therefore investigated whether currently used methods of CTF correction are also effective in restoring the single-sideband image information that becomes displaced (delocalized) by half (or more) the diameter of a particle of finite size. Computer simulations are used to show that restoration either by"phase flipping" or by multiplying by the CTF recovers only about half of the delocalized information. The other half of the delocalized information goes into a doubly defocused"twin" image of the type produced during optical reconstruction of an in-line hologram. Restoration with a Wiener filter is effective in recovering the delocalized information only when the signal-to-noise ratio (S/N) is orders of magnitude higher than that which exists in low-dose images of biological specimens, in which case the Wiener filter approaches division by the CTF (i.e. the formal inverse). For realistic values of the S/N, however, the"twin image" problem seenwith a Wiener filter is very similar to that seen when either phase flipping or multiplying by the CTF are used for restoration. The results of these simulations suggest that CTF correction is a poor alternative to using a Zernike-type phase plate when imaging biological specimens, in which case the images can be recorded in a close-to-focus condition, and delocalization of high-resolution information is thus minimized