Ertapenem-Induced Encephalopathy in a Patient With Normal Renal Function

Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient’s symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction. Since clinical evidence strongly suggested ertapenem causality, we utilized the Naranjo Scale to estimate the probability of an adverse drug reaction to ertapenem. Our patient received a Naranjo Scale score of 7, suggesting a probable adverse drug reaction, with a reasonable temporal sequence to support our conclusion

Improved protein structure prediction using potentials from deep learning

Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence1. This problem is of fundamental importance as the structure of a protein largely determines its function2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction5 (CASP13)—a blind assessment of the state of the field—AlphaFold created high-accuracy structures (with template modelling (TM) scores6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined7

Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13)

We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13 Submissions were made by three free-modelling methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on-par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 free-modelling assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group. (An average GDT_TS of 61.4.) The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 free-modelling domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods

Nuclear dependence of the transverse single-spin asymmetry in the production of charged hadrons at forward rapidity in polarized p+pp+p, p+p+Al, and p+p+Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively-charged hadrons in polarized $p^{\uparrow}+p$, $p^{\uparrow}+$Al and $p^{\uparrow}+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. The measurements have been performed at forward rapidity ($1.4<\eta<2.4$) over the range of $1.8<p_{T}<7.0$ GeV$/c$ and $0.1<x_{F}<0.2$. We observed a positive asymmetry $A_{N}$ for positively-charged hadrons in \polpp collisions, and a significantly reduced asymmetry in $p^{\uparrow}$+$A$ collisions. These results reveal a nuclear dependence of charged hadron $A_N$ in a regime where perturbative techniques are relevant. These results provide new opportunities to use \polpA collisions as a tool to investigate the rich phenomena behind TSSAs in hadronic collisions and to use TSSA as a new handle in studying small-system collisions.Comment: 303 authors from 66 institutions, 9 pages, 2 figures, 1 table. v1 is version accepted for publication in Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions

Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation

Measurements of double-helicity asymmetries in inclusive J/ψJ/\psi production in longitudinally polarized p+pp+p collisions at s=510\sqrt{s}=510 GeV

We report the double helicity asymmetry, $A_{LL}^{J/\psi}$, in inclusive $J/\psi$ production at forward rapidity as a function of transverse momentum $p_T$ and rapidity $|y|$. The data analyzed were taken during $\sqrt{s}=510$ GeV longitudinally polarized $p$$+$$p$ collisions at the Relativistic Heavy Ion Collider (RHIC) in the 2013 run using the PHENIX detector. At this collision energy, $J/\psi$ particles are predominantly produced through gluon-gluon scatterings, thus $A_{LL}^{J/\psi}$ is sensitive to the gluon polarization inside the proton. We measured $A_{LL}^{J/\psi}$ by detecting the decay daughter muon pairs $\mu^+ \mu^-$ within the PHENIX muon spectrometers in the rapidity range $1.2<|y|<2.2$. In this kinematic range, we measured the $A_{LL}^{J/\psi}$ to be $0.012 \pm 0.010$~(stat)~$\pm$~$0.003$(syst). The $A_{LL}^{J/\psi}$ can be expressed to be proportional to the product of the gluon polarization distributions at two distinct ranges of Bjorken $x$: one at moderate range $x \approx 0.05$ where recent RHIC data of jet and $\pi^0$ double helicity spin asymmetries have shown evidence for significant gluon polarization, and the other one covering the poorly known small-$x$ region $x \approx 2\times 10^{-3}$. Thus our new results could be used to further constrain the gluon polarization for $x< 0.05$.Comment: 335 authors, 10 pages, 4 figures, 3 tables, 2013 data. Version accepted for publication by Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm