Using a novel iterative structure factor retrieval algorithm, here I show that electron density can be directly calculated from solution scattering data without modeling. The algorithm was validated ...with experimental data from 12 different biological macromolecules. This approach avoids many of the assumptions limiting the resolution and accuracy of modeling algorithms by explicitly calculating electron density. This algorithm can be applied to a wide variety of molecular systems.
Small‐angle scattering (SAS) probes the size and shape of particles at low resolution through the analysis of the scattering of X‐rays or neutrons passing through a solution of particles. One ...approach to extracting structural information from SAS data is the indirect Fourier transform (IFT). The IFT approach parameterizes the real‐space pair distribution function P(r) of a particle using a set of basis functions, which simultaneously determines the scattering profile I(q) using corresponding reciprocal‐space basis functions. This article presents an extension of an IFT algorithm proposed by Moore J. Appl. Cryst. (1980), 13, 168–175 which used a trigonometric series to describe the basis functions, where the real‐space and reciprocal‐space basis functions are Fourier mates. An equation is presented relating the Moore coefficients to the intensities of the SAS profile at specific positions, as well as a series of new equations that describe the size and shape parameters of a particle from this distinct set of intensity values. An analytical real‐space regularizer is derived to smooth the P(r) curve and ameliorate systematic deviations caused by series termination. Regularization is commonly used in IFT methods though not described in Moore's original approach, which is particularly susceptible to such effects. The algorithm is provided as a script, denss.fit_data.py, as part of the DENSS software package for SAS, which includes both command line and interactive graphical interfaces. Results of the program using experimental data show that it is as accurate as, and often more accurate than, existing tools.
An indirect Fourier transform method is presented which describes a solution scattering profile from a reduced set of intensities. Equations are derived to fit the experimental profile using least squares and to calculate commonly used size and shape parameters directly from the reduced set of intensities, along with associated uncertainties. An analytical equation is derived enabling regularization of the real‐space pair distribution function. Convenient software is provided to perform all described calculations.
Ab initio modeling methods have proven to be powerful means of interpreting solution scattering data. In the absence of atomic models, or complementary to them, ab initio modeling approaches can be ...used for generating low-resolution particle envelopes using only solution scattering profiles. Recently, a new ab initio reconstruction algorithm has been introduced to the scientific community, called DENSS. DENSS is unique among ab initio modeling algorithms in that it solves the inverse scattering problem, i.e., the 1D scattering intensities are directly used to determine the 3D particle density. The reconstruction of particle density has several advantages over conventional uniform density modeling approaches, including the ability to reconstruct a much wider range of particle types and the ability to visualize low-resolution density fluctuations inside the particle envelope. In this chapter we will discuss the theory behind this new approach, how to use DENSS, and how to interpret the results. Several examples with experimental and simulated data will be provided.
To describe the use of intraprocedural motor evoked potential (MEP) monitoring to minimize risk of neural injury during percutaneous cryoablation of perineural musculoskeletal tumors.
A ...single-institution retrospective review of cryoablation procedures performed to treat perineural musculoskeletal tumors with the use of MEP monitoring between May 2011 and March 2013 yielded 59 procedures to treat 64 tumors in 52 patients (26 male). Median age was 61 years (range, 4-82 y). Tumors were located in the spine (n = 27), sacrum (n = 3), retroperitoneum (n = 4), pelvis (n = 22), and extremities (n = 8), and 21 different tumor histologies were represented. Median tumor size was 4.0 cm (range, 0.8-15.0 cm). Total intravenous general anesthesia, computed tomographic guidance, and transcranial MEP monitoring were employed. Patient demographics, tumor characteristics, MEP findings, and clinical outcomes were assessed.
Nineteen of 59 procedures (32%) resulted in decreases in intraprocedural MEPs, including 15 (25%) with transient decreases and four (7%) with persistent decreases. Two of the four patients with persistent MEP decreases (50%) had motor deficits following ablation. No functional motor deficit developed in a patient with transient MEP decreases or no MEP change. The risk of major motor injury with persistent MEP changes was significantly increased versus transient or no MEP change (P = .0045; relative risk, 69.8; 95% confidence interval, 5.9 to > 100). MEP decreases were 100% sensitive and 70% specific for the detection of motor deficits.
Persistent MEP decreases correlate with postprocedural sustained motor deficits. Intraprocedural MEP monitoring helps predict neural injury and may improve patient safety during cryoablation of perineural musculoskeletal tumors.
To determine the incidence of major adverse events related to a large volume of image-guided liver biopsies performed at our institution over a 12-year period and to identify risk factors for major ...bleeding events.
A retrospective analysis of an internally maintained biopsy registry was performed. The analysis revealed that 6613 image-guided liver biopsies were performed in 5987 adult patients between December 7, 2001, and December 31, 2013. Liver biopsies were performed using real-time ultrasound guidance and a spring-loaded biopsy device, with rare exceptions. Adverse events considered major and included in this study were hematoma, infection, pneumothorax, hemothorax, and death. Using data from the biopsy registry, we evaluated statistically significant risk factors (P<.05) for hematoma related to image-guided liver biopsy, including coagulation status, biopsy technique, and medications.
A total of 49 acute and delayed major adverse events (0.7%) occurred after 6613 liver biopsy events. The incidence of hematoma requiring transfusion and/or angiographic intervention was 0.5% (34 of 6613). The incidence of infection was 0.1% (8 of 6613), and that of hemothorax was 0.06% (4 of 6613). No patient (0%) incurred a pneumothorax after biopsy. Three patients (0.05%) died within 30 days of liver biopsy, 1 being directly related to biopsy. Thirty-eight of 46 major adverse events (83%) presented acutely (within 24 hours). More than 2 biopsy passes, platelets 50,000/μL or less, and female sex were statistically significant risk factors for postbiopsy hemorrhage.
Image-guided liver biopsy performed by subspecialized interventionalists at a tertiary medical center is safe when the platelet count is greater than 50,000/μL. With appreciation of specific risk factors, safety outcomes of this procedure can be optimized in both general and specialized centers.
Conferring legal personhood on purely synthetic entities is a very real legal possibility, one under consideration presently by the European Union. We show here that such legislative action would be ...morally unnecessary and legally troublesome. While AI legal personhood may have some emotional or economic appeal, so do many superficially desirable hazards against which the law protects us. We review the utility and history of legal fictions of personhood, discussing salient precedents where such fictions resulted in abuse or incoherence. We conclude that difficulties in holding “electronic persons” accountable when they violate the rights of others outweigh the highly precarious moral interests that AI legal personhood might protect.
Solution scattering techniques, such as small- and wide-angle X-ray scattering (SWAXS), provide valuable insights into the structure and dynamics of biological macromolecules in solution. In this ...study, we present an approach to accurately predict solution X-ray scattering profiles at wide angles from atomic models by generating high-resolution electron density maps. Our method accounts for the excluded volume of bulk solvent by calculating unique adjusted atomic volumes directly from the atomic coordinates. This approach eliminates the need for one of the free fitting parameters commonly used in existing algorithms, resulting in improved accuracy of the calculated SWAXS profile. An implicit model of the hydration shell is generated that uses the form factor of water. Two parameters, namely the bulk solvent density and the mean hydration shell contrast, are adjusted to best fit the data. Results using eight publicly available SWAXS profiles show high-quality fits to the data. In each case, the optimized parameter values show small adjustments demonstrating that the default values are close to the true solution. Disabling parameter optimization produces significantly more accurate predicted scattering profiles compared to the leading software. The algorithm is computationally efficient, comparable to the leading software and up to 10 times faster for large molecules. The algorithm is encoded in a command line script called denss.pdb2mrc.py and is available open source as part of the DENSS v1.7.0 software package. In addition to improving the ability to compare atomic models to experimental SWAXS data, these developments pave the way for increasing the accuracy of modeling algorithms using SWAXS data and decreasing the risk of overfitting.
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