Quantum Simulators: Architectures and Opportunities

Quantum simulators are a promising technology on the spectrum of quantum devices from specialized quantum experiments to universal quantum computers. These quantum devices utilize entanglement and many-particle behavior to explore and solve hard scientific, engineering, and computational problems. Rapid development over the last two decades has produced more than 300 quantum simulators in operation worldwide using a wide variety of experimental platforms. Recent advances in several physical architectures promise a golden age of quantum simulators ranging from highly optimized special purpose simulators to flexible programmable devices. These developments have enabled a convergence of ideas drawn from fundamental physics, computer science, and device engineering. They have strong potential to address problems of societal importance, ranging from understanding vital chemical processes, to enabling the design of new materials with enhanced performance, to solving complex computational problems. It is the position of the community, as represented by participants of the National Science Foundation workshop on “Programmable Quantum Simulators,” that investment in a national quantum simulator program is a high priority in order to accelerate the progress in this field and to result in the first practical applications of quantum machines. Such a program should address two areas of emphasis: (1) support for creating quantum simulator prototypes usable by the broader scientific community, complementary to the present universal quantum computer effort in industry; and (2) support for fundamental research carried out by a blend of multi-investigator, multidisciplinary collaborations with resources for quantum simulator software, hardware, and education.This document is a summary from a U.S. National Science Foundation supported workshop held on 16–17 September 2019 in Alexandria, VA. Attendees were charged to identify the scientific and community needs, opportunities, and significant challenges for quantum simulators over the next 2–5 years

Novel post-synthetic generation, isomeric resolution, and characterization of Fapy-dG within oligodeoxynucleotides: differential anomeric impacts on DNA duplex properties

Accumulation of damaged guanine nucleobases within genomic DNA, including the imidazole ring opened N6-(2-Deoxy-α,β-D-erythro-pentafuranosyl)-2,6-diamino-4-hydroxy-5-formylamidopyrimidine (Fapy-dG), is associated with progression of age-related diseases and cancer. To evaluate the impact of this mutagenic lesion on DNA structure and energetics, we have developed a novel synthetic strategy to incorporate cognate Fapy-dG site-specifically within any oligodeoxynucleotide sequence. The scheme involves the synthesis of an oligonucleotide precursor containing a 5-nitropyrimidine moiety at the desired lesion site via standard solid-phase procedures. Following deprotection and isolation, the Fapy-dG lesion is generated by catalytic hydrogenation and subsequent formylation. NMR assignment of the Fapy-dG lesion (X) embedded within a TXT trimer reveals the presence of rotameric and anomeric species. The latter have been characterized by synthesizing the tridecamer oligodeoxynucleotide d(GCGTACXCATGCG) harboring Fapy-dG as the central residue and developing a protocol to resolve the isomeric components. Hybridization of the chromatographically isolated fractions with their complementary d(CGCATGCGTACGC) counterpart yields two Fapy-dG·C duplexes that are differentially destabilized relative to the canonical G·C parent. The resultant duplexes exhibit distinct thermal and thermodynamic profiles that are characteristic of α- and β-anomers, the former more destabilizing than the latter. These anomer-specific impacts are discussed in terms of differential repair enzyme recognition, processing and translesion synthesis

Tyrannobdella rex N. Gen. N. Sp. and the Evolutionary Origins of Mucosal Leech Infestations

BACKGROUND: Leeches have gained a fearsome reputation by feeding externally on blood, often from human hosts. Orificial hirudiniasis is a condition in which a leech enters a body orifice, most often the nasopharyngeal region, but there are many cases of leeches infesting the eyes, urethra, vagina, or rectum. Several leech species particularly in Africa and Asia are well-known for their propensity to afflict humans. Because there has not previously been any data suggesting a close relationship for such geographically disparate species, this unnerving tendency to be invasive has been regarded only as a loathsome oddity and not a unifying character for a group of related organisms. PRINCIPAL FINDINGS: A new genus and species of leech from Perú was found feeding from the nasopharynx of humans. Unlike any other leech previously described, this new taxon has but a single jaw with very large teeth. Phylogenetic analyses of nuclear and mitochondrial genes using parsimony and Bayesian inference demonstrate that the new species belongs among a larger, global clade of leeches, all of which feed from the mucosal surfaces of mammals. CONCLUSIONS: This new species, found feeding from the upper respiratory tract of humans in Perú, clarifies an expansion of the family Praobdellidae to include the new species Tyrannobdella rex n. gen. n. sp., along with others in the genera Dinobdella, Myxobdella, Praobdella and Pintobdella. Moreover, the results clarify a single evolutionary origin of a group of leeches that specializes on mucous membranes, thus, posing a distinct threat to human health

DNA adducts of aristolochic acid II: total synthesis and site-specific mutagenesis studies in mammalian cells

Aristolochic acids I and II (AA-I, AA-II) are found in all Aristolochia species. Ingestion of these acids either in the form of herbal remedies or as contaminated wheat flour causes a dose-dependent chronic kidney failure characterized by renal tubulointerstitial fibrosis. In ∼50% of these cases, the condition is accompanied by an upper urinary tract malignancy. The disease is now termed aristolochic acid nephropathy (AAN). AA-I is largely responsible for the nephrotoxicity while both AA-I and AA-II are genotoxic. DNA adducts derived from AA-I and AA-II have been isolated from renal tissues of patients suffering from AAN. We describe the total synthesis, de novo, of the dA and dG adducts derived from AA-II, their incorporation site-specifically into DNA oligomers and the splicing of these modified oligomers into a plasmid construct followed by transfection into mouse embryonic fibroblasts. Analysis of the plasmid progeny revealed that both adducts blocked replication but were still partly processed by DNA polymerase(s). Although the majority of coding events involved insertion of correct nucleotides, substantial misincorporation of bases also was noted. The dA adduct is significantly more mutagenic than the dG adduct; both adducts give rise, almost exclusively, to misincorporation of dA, which leads to AL-II-dA→T and AL-II-dG→T transversions

Sampling and refinement protocols for template-based macrocycle docking: 2018 D3R Grand Challenge 4

We describe a new template-based method for docking flexible ligands such as macrocycles to proteins. It combines Monte-Carlo energy minimization on the manifold, a fast manifold search method, with BRIKARD for complex flexible ligand searching, and with the MELD accelerator of Replica-Exchange Molecular Dynamics simulations for atomistic degrees of freedom. Here we test the method in the Drug Design Data Resource blind Grand Challenge competition. This method was among the best performers in the competition, giving sub-angstrom prediction quality for the majority of the targets

Chapter VI: Land-use and landscape management

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