Nonclassical Structure Research Articles

Isolable T-Shaped Planar Silyl Anion.

Silyl anions have garnered significant attention due to their synthetic abilities. However, previously reported silyl anions have been limited to either trigonal-pyramidal or trigonal-planar geometries, which confine them primarily as nucleophiles in substitution reactions. Herein, we report the isolation of the unprecedented T-shaped planar silyl anion salt 2 by employment of a geometrically constrained triamido pincer ligand. Theoretical calculations disclosed that the silicon centre in 2 possesses both a lone pair of electrons and an empty 3pz orbital. In addition to nucleophilic substitution reactions with Ph3PAuCl and W(CO)6, 2 readily undergoes oxidative additions with CO2 and 2,6-dimethylphenylisonitrile at room temperature. Furthermore, under mild conditions, compound 2 cleaves Csp2-H, Csp2-H, and H-H bonds in 1,2,4,5-tetrafluorobenzene, an intramolecular iPr group, and dihydrogen, representing the first examples of C-H and H-H activations mediated by a silyl anion, respectively. This work unveils new reactivity of silyl anions owing to the non-classical geometry and electronic structure.

Polar covalent apex-base bonding in borapyramidanes probed by solid-state NMR and DFT calculations.

Pyramidane molecules have attracted chemists for many decades due to their regular shape, high symmetry and their correspondence in the macroscopic world. Recently, experimental access to a number of examples has been reported, in particular the rarely reported square pyramidal bora[4]pyramidanes. To describe the bonding situation of the nonclassical structure of pyramidanes, we present solid-state Nuclear Magnetic Resonance (NMR) as a versatile tool for deciphering such bonding properties for three now accessible bora[4]pyramidane and dibora[5]pyramidane molecules. 11 B solid-state NMR spectra indicate that the apical boron nuclei in these compounds are strongly shielded (around -50 ppm vs. BF3 -Et2 O complex) and possess quadrupolar coupling constants of less than 0.9 MHz pointing to a rather high local symmetry. 13 C-11 B spin-spin coupling constants have been explored as a measure of the bond covalency in the borapyramidanes. While the carbon-boron bond to the -B(C6 F5 )2 substituents of the base serves as an example for a classical covalent 2-center-2-electron (2c-2e) sp2 -carbon-sp2 -boron σ-bond with 1 J(13 C-11 B) coupling constants in the order of 75 Hz, those of the boron(apical)-carbon(basal) bonds in the pyramid are too small to measure. These results suggest that these bonds have a strongly ionic character, which is also supported by quantum-chemical calculations.

Embodied Imagination: Lakoff and Johnson’s Experientialist View of Conceptual Understanding

This paper reviews an embodied or experientialist view of conceptual understanding. It focuses on George Lakoff and Mark Johnson’s theory of embodied cognition and its framing of human conceptualization and reasoning in terms of embodied imagination. These ideas are summarized as ten basic claims: (a) objectivist assumptions are problematic; (b) many human categories have non-classical structure; (c) conceptual systems consist of cognitive models; (d) thinking utilizes frames, metonymies, and prototypes; (e) metaphor is prevalent and primarily conceptual; (f) image schemas structure our experiences; (g) the mind is embodied; (h) abstract thought is largely metaphorical; (i) truth is relative to embodied understanding; and (j) philosophy should be empirically responsible. Lakoff and Johnson’s theory of embodied cognition offers a view of conceptual understanding that is cognitively realistic (or empirically responsible), biologically plausible, and self-critical, while providing adequate theories of meaning and truth grounded in embodied experience.

Prediction of strand-specific and cell-type-specific G-quadruplexes based on high-resolution CUT&Tag data.

G-quadruplex (G4), a non-classical deoxyribonucleic acid structure, is widely distributed in the genome and involved in various biological processes. In vivo, high-throughput sequencing has indicated that G4s are significantly enriched at functional regions in a cell-type-specific manner. Therefore, the prediction of G4s based on computational methods is necessary instead of the time-consuming and laborious experimental methods. Recently, G4 CUT&Tag has been developed to generate higher-resolution sequencing data than ChIP-seq, which provides more accurate training samples for model construction. In this paper, we present a new dataset construction method based on G4 CUT&Tag sequencing data and an XGBoost prediction model based on the machine learning boost method. The results show that our model performs well within and across cell types. Furthermore, sequence analysis indicates that the formation of G4 structure is greatly affected by the flanking sequences, and the GC content of the G4 flanking sequences is higher than non-G4. Moreover, we also identified G4 motifs in the high-resolution dataset, among which we found several motifs for known transcription factors (TFs), such as SP2 and BPC. These TFs may directly or indirectly affect the formation of the G4 structure.

The Role of the Redox Non-Innocent Hydroxyl Ligand in the Activation of O2 Performed by [Ni(H)(OH)

The cationic complex [Ni(H)(OH)]+ was previously found to activate dioxygen and methane in gas phase under single collision conditions. These remarkable reactivities were thought to originate from a non-classical electronic structure, where the Ni-center adopts a Ni(II), instead of the classically expected Ni(III) oxidation state by formally accepting an electron from the hydroxo ligand, which formally becomes a hydroxyl radical in the process. Such radicaloid oxygen moieties are envisioned to easily react with otherwise inert substrates, mimicking familiar reactivities of free radicals. In this study, the reductive activation of dioxygen by [Ni(H)(OH)]+ to afford the hydroperoxo species was investigated using coupled cluster, multireference ab initio and density functional theory calculations. Orbital and wave function analyses indicate that O2 binding tranforms the aforementioned non-classical electronic structure to a classical Ni(III)-hydroxyl system, before O2 reduction takes place. Remarkably, we found no evidence for a direct involvement of the radicaloid hydroxyl in the reaction with O2 , as is often assumed. The function of the redox non-innocent character of the activator complex is to protect the reactive electronic structure until the complex engages O2 , upon which a dramatic electronic reorganization releases internal energy and drives the chemical reaction to completion.

Artificial General Intelligence and Noncomputability: A Dynamical Framework

Achieving genuine (human-level) artificial general intelligence (AGI) is one of the major goals of computer science, engineering, psychology, neuroscience, and mathematics. In this paper, we critically reexamine the relation between natural intelligence and artificial intelligence at a fairly general theoretical level. After identifying four major structural themes in natural intelligence, we move to the issue of AGI implementation through physical computing machines. Motivated by Penrose’s Gödelian argument refuting the thesis of AGI realizability via Turing machines, we formulate several theses on the noncomputable character of AGI systems. In particular, we support the claim that infinitary noncomputability might constitute a viable path toward future AGI implementations, especially if coupled with nonlocality and a nonclassical probabilistic structure such as those in the quantum world. A theoretical mathematical framework for realizing AGI through non-Markovian stochastic dynamic systems is then presented and illustrated by describing multi-agent AGI assemblages comprised of interconnected dynamic agents. We envision that such networked dynamical assemblages might be powered by noncomputable physics or arranged in an infinitary structure.

Identification of Active Compounds against Melanoma Growth by Virtual Screening for Non-Classical Human DHFR Inhibitors.

Antifolates such as methotrexate (MTX) have been largely known as anticancer agents because of their role in blocking nucleic acid synthesis and cell proliferation. Their mechanism of action lies in their ability to inhibit enzymes involved in the folic acid cycle, especially human dihydrofolate reductase (hDHFR). However, most of them have a classical structure that has proven ineffective against melanoma, and, therefore, inhibitors with a non-classical lipophilic structure are increasingly becoming an attractive alternative to circumvent this clinical resistance. In this study, we conducted a protocol combining virtual screening (VS) and cell-based assays to identify new potential non-classical hDHFR inhibitors. Among 173 hit compounds identified (average logP = 3.68; average MW = 378.34 Da), two-herein, called C1 and C2-exhibited activity against melanoma cell lines B16 and A375 by MTT and Trypan-Blue assays. C1 showed cell growth arrest (39% and 56%) and C2 showed potent cytotoxic activity (77% and 51%) in a dose-dependent manner. The effects of C2 on A375 cell viability were greater than MTX (98% vs 60%) at equivalent concentrations and times. Our results indicate that the integrated in silico/in vitro approach provided a benchmark to identify novel promising non-classical DHFR inhibitors showing activity against melanoma cells.

Hopf-Galois module structure of quartic Galois extensions of Q

Given a quartic Galois extension $L/\mathbb{Q}$ of number fields and a Hopf-Galois structure $H$ on $L/\mathbb{Q}$, we study the freeness of the ring of integers $\mathcal{O}_L$ as module over the associated order $\mathfrak{A}_H$ in $H$. For the classical Galois structure $H_c$, we know by Leopoldt's theorem that $\mathcal{O}_L$ is $\mathfrak{A}_{H_c}$-free. If $L/\mathbb{Q}$ is cyclic, it admits a unique non-classical Hopf-Galois structure, whereas if it is biquadratic, it admits three such Hopf-Galois structures. In both cases, we obtain that freeness depends on the solvability in $\mathbb{Z}$ of certain generalized Pell equations. We shall translate some results on Pell equations into results on the $\mathfrak{A}_H$-freeness of $\mathcal{O}_L$.

Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

ABSTRACT Inducing a full antitumor immune response in the tumor microenvironment (TME) is essential for successful cancer immunotherapy. Here, we report that an oncolytic adenovirus carrying mIL-15 (Ad-IL15) can effectively induce antitumor immune response and inhibit tumor growth in a mouse model of cancer. We found that Ad-IL15 facilitated the activation and infiltration of immune cells, including dendritic cells (DCs), T cells and natural killer (NK) cells, in the TME. Unexpectedly, we observed that Ad-IL15 also induced vascular normalization and tertiary lymphoid structure formation in the TME. Moreover, we demonstrated these Ad-IL15-induced changes in the TME were depended on the Ad-IL15-induced activation of the STING-TBK1-IRF3 pathway in DCs. Taken together, our findings suggest that Ad-IL15 is a candidate for cancer immunotherapy that promotes immune cell activation and infiltration, tumor vascular normalization and tertiary lymphoid structure formation in the TME.

Fast Near Ab Initio Potential Energy Surfaces Using Machine Learning.

A machine-learning based approach for evaluating potential energies for quantum mechanical studies of properties of the ground and excited vibrational states of small molecules is developed. This approach uses the molecular-orbital-based machine learning (MOB-ML) method to generate electronic energies with the accuracy of CCSD(T) calculations at the same cost as a Hartree-Fock calculation. To further reduce the computational cost of the potential energy evaluations without sacrificing the CCSD(T) level accuracy, GPU-accelerated Neural Network Potential Energy Surfaces (NN-PES) are trained to geometries and energies that are collected from small-scale Diffusion Monte Carlo (DMC) simulations, which are run using energies evaluated using the MOB-ML model. The combined NN+(MOB-ML) approach is used in variational calculations of the ground and low-lying vibrational excited states of water and in DMC calculations of the ground states of water, CH5+, and its deuterated analogues. For both of these molecules, comparisons are made to the results obtained using potentials that were fit to much larger sets of electronic energies than were required to train the MOB-ML models. The NN+(MOB-ML) approach is also used to obtain a potential surface for C2H5+, which is a carbocation with a nonclassical equilibrium structure for which there is currently no available potential surface. This potential is used to explore the CH stretching vibrations, focusing on those of the bridging hydrogen atom. For both CH5+ and C2H5+ the MOB-ML model is trained using geometries that were sampled from an AIMD trajectory, which was run at 350 K. By comparison, the structures sampled in the ground state calculations can have energies that are as much as ten times larger than those used to train the MOB-ML model. For water a higher temperature AIMD trajectory is needed to obtain accurate results due to the smaller thermal energy. A second MOB-ML model for C2H5+ was developed with additional higher energy structures in the training set. The two models are found to provide nearly identical descriptions of the ground state of C2H5+.

The development of an iridium(III) complex functionalized G-quadruplex probe for the stability of G-quadruplex and lifetime image in cytoplasm

G-quadruplex (G4) is widely known as a non-classical secondary structure of nucleic acid. With the in-depth study of G4, it is an urgent need for a phosphorescent probe with a high G4 binding ability to evaluate the level of G4 in the cytoplasm. Thus, this study designed and synthesized Ir-PDP where an Ir(III) complex was used as a phosphorescent emitter. Meanwhile, two installed PDPs (pyridostatin derivatives) were used to improve the combination ability with G4 and reduced the cytotoxicity of the Ir(III) complex. Compared with other nucleic acid secondary structures, Ir-PDP produced a higher phosphorescence lifetime after interacting with G4. Ir-PDP was distributed in the cytoplasm of living cells, and two-photon phosphorescence lifetime imaging can detect the binding events of the probe in the cytoplasm. The addition of G4 binder PDS significantly regulated cytoplasmic phosphorescence lifetime. The project explored a new sensing pathway to observe the binding manners of probes in the cytoplasm through the phosphorescence lifetime of probes.

Surveying Structural Complexity in Quantum Many-Body Systems

Quantum many-body systems exhibit a rich and diverse range of exotic behaviours, owing to their underlying non-classical structure. These systems present a deep structure beyond those that can be captured by measures of correlation and entanglement alone. Using tools from complexity science, we characterise such structure. We investigate the structural complexities that can be found within the patterns that manifest from the observational data of these systems. In particular, using two prototypical quantum many-body systems as test cases - the one-dimensional quantum Ising and Bose-Hubbard models - we explore how different information-theoretic measures of complexity are able to identify different features of such patterns. This work furthers the understanding of fully-quantum notions of structure and complexity in quantum systems and dynamics.

Experimental and numerical analysis of vibration-based hybrid energy harvesting from non-classical beam structures

It is known that the displacement and stress on beams will directly affect the energy harvesting performance. For this purpose, structural changes are made on the beam elements. Behaviours of these beam structures are investigated by designing different non-classical beam geometries. This study examines vibration-based electromagnetic and piezoelectric energy harvesting from the non-classical beam structures under various conditions. Before analysing the non-classical beam structure, studies are performed for a classical beam for electromagnetic and piezoelectric energy harvesting studies. In the electromagnetic energy harvesting analysis, the effects of magnitude of magnetic field and the distance between the coil and the permanent magnet on the harvesting performance are studied by free vibration experiments. In this regard, a neodymium permanent magnet is attached to the vibrating aluminium beam endpoint. During the free vibration period, the coil and the magnet interact closely. As a result, a voltage output is obtained by inducing an electric field on the coil side. Secondly, voltage outputs of piezoelectric energy harvesting structures are experimentally evaluated for a classical beam and used for the verification of numerical simulations. Using the verified numerical simulations, new types of beam structures so-called non-classical beams are designed to obtain higher voltage outputs. Finally, by introducing the phenomenon of continuous vibration with the effect of air, the hybrid energy performance is analyzed for the proposed structure. The continuous vibration is created by the air-flow on the square galloping geometry.

The typicality effect in basic needs

According to the so-called Classical Theory, concepts are mentally represented by individually necessary and jointly sufficient application conditions. One of the principal empirical objections against this view stems from evidence that people judge some instances of a concept to be more typical than others. In this paper we present and discuss four empirical studies that investigate the extent to which this ‘typicality effect’ holds for the concept of basic needs. Through multiple operationalizations of typicality, our studies yielded evidence for a strong effect of this kind: (1) Participants tended to recall the same core examples of the concept in a free-listing task. (2) They judged some basic needs to be more typical than others. (3) The items that were judged to be more typical were listed more frequently in the free-listing task. (4) These items were listed earlier on in the free-listing task. (5) Typical basic needs, as well as non needs, were classified faster than atypical basic needs in a reaction time study. These findings suggest that the concept of basic needs may have a non-classical (e.g., exemplar or prototype) structure. If so, the quest for a simple and robust intensional analysis of the concept may be futile.

Charge-Inverted Hydrogen-Bridged Bond in HCa(μ-H)3E (E = Si, Ge, and Sn): Matrix Isolation Infrared Spectroscopic and Theoretical Studies

Matrix isolation infrared spectroscopy combined with quantum-chemical calculations were employed to study the reactions of calcium atoms with silane, germane, and stannane in a 4 K argon matrix. The ion pairs [HCa]+ and [EH3]- (E = Si, Ge, and Sn) in both the classical structure HCaEH3 and the bridged structure HCa(μ-H)3E were identified based on the H/D isotopic substitution experiments and quantum-chemical calculations. The results show that the reaction between ground-state Ca and EH4 proceeds inefficiently, and only after the photolytic activation of Ca atoms to the Ca(1P:4s4p) state does insertion occur to give HCaEH3, which rearranges to HCa(μ-H)3E upon photolysis. Topological analysis of the electronic structure suggests that the nonclassical structure HCa(μ-H)3E is formed by the electrostatic interaction with charge-inverted hydrogen bridge bond, while HCaEH3 is dominated by (HCa)+(EH3)- ion pair interactions.

Optimal Local and Remote Controllers With Unreliable Uplink Channels: An Elementary Proof

Recently, a model of a decentralized control system with local and remote controllers connected over unreliable channels was presented in [1] . The model has a nonclassical information structure that is not partially nested. Nonetheless, it is shown in [1] that the optimal control strategies are linear functions of the state estimate (which is a nonlinear function of the observations). Their proof is based on a fairly sophisticated dynamic programming argument. In this article, we present an alternative and elementary proof of the result which uses common information-based conditional independence and completion of squares.

Study on flow separation and transition of the airfoil in low Reynolds number

As typical flow characteristics in a low Reynolds number, laminar separation bubbles (LSBs) and transition to turbulence over airfoils have been extensively studied in recent years. In order to analyze their flow mechanism, numerical investigation using the finite volume method to solve the Reynolds averaged Navier-Stokes equations with a transition Shear Stress Transport (SST) four-equation transition model is performed in this work, combined with the experimental study facilitated by the oil film interferometry technique. Specifically, the transition SST four-equation transition model is solved to simulate the separation location and LSB structure at low Reynolds numbers on a Wortmann FX63-137 airfoil. Good agreement is obtained between the numerical simulation and experimental measurements regarding the separation, transition and reattachment location, aerodynamic coefficients, and overall flow structures. At higher Reynolds numbers of 200 000 and 300 000, similar bubble structures on the airfoil surface are observed, and the location of the bubble moves toward the leading edge of the airfoil by increasing the angle of attack. However, in Reynolds numbers ranging from 300 000 to 500 000, significant changes of the laminar flow separation structures emerge. The flow structure changes from the classical laminar separation bubble to the nonclassical separation flow structure that is composed of a major vortex 1(V1) and a minor vortex 2(V2). Due to the small distance between V1 and V2, it is difficult to distinguish the delicate structure of the two separation bubbles from the classical laminar separation bubble by the experimental method.

Cyclobutane dication, (CH2)4 2+: a model for a two-electron four-center (2e-4c) Woodward-Hoffmann frozen transition state.

The structures of the elusive cyclobutane dication, (CH2)42+, were investigated at the MP2/cc-pVTZ and CCSD(T)/cc-pVTZ levels. Calculations show that the two-electron four-center (2e-4c) bonded structure 1 involving four carbon atoms is a minimum. The structure contains formally two tetracoordinate and two pentacoordinate carbons. The non-classical σ-delocalized structure can be considered as a prototype for a 2e-4c Woodward–Hoffmann frozen transition state. The planar rectangular shaped structure 2 with a 2e-4c bond was found not to be a minimum.

2560. Multispecies Outbreak of KPC-2 Producing Enterobacteriaceae in a Chilean Pediatric Hospital

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) are a critical global health problem. We detected a surge of CRE cases in a pediatric hospital in Chile, a country with a low endemicity of KPC-producing organisms. Herein, we describe the molecular epidemiology of this outbreak.MethodsCRE isolates from clinical specimens and surveillance rectal swabs (obtained using chromID CARBA SMART agar, BioMerieux) of pediatric patients were collected from July 2015 to January 2017. Species identity was confirmed by MALDI-TOF. Carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like) were detected by multiplex PCR, followed by amplification and sequencing of the blaKPC allele. Conjugation experiments were conducted with representative species as donors and sodium azide-resistant E. coli J53 as recipient. PCR-based plasmid typing (PBRT Diatheva kit) was then performed on donors and recipients. For K. pneumoniae, genetic relatedness was investigated by PFGE, multilocus sequence typing and wzi typing.ResultsSixty-one CRE clinical and surveillance isolates were obtained from 49 patients aged 17 days to 16 years. blaKPC-2 was present in 57/62 isolates; no other carbapenemases were found. For 11 patients, multiple cultures were obtained; 4/11 had more than one KPC-harboring species. KPC-harboring isolates displayed ertapenem MICs ranging from 1 to >8 mg/L. Preliminary analyses suggest that blaKPC-2 is contained within a nonclassical Tn4401 structure (lacking the upstream promoter). Mating experiments indicate that blaKPC-2 is carried by a conjugative IncN backbone plasmid. Interestingly, K. pneumoniae isolates were nonclonal by PFGE and belonged to multiple STs unrelated to CG258 (ST34, ST36, among others) and different wzi types (37, 154, among others). ConclusionWe report a multispecies outbreak of KPC-2 producing CRE in children mainly driven by horizontal dissemination of a promiscuous IncN plasmid. The nonclonal, multispecies nature of this outbreak provides insights into the complex dynamics of KPC dissemination in countries like Chile, where the clonal spread of highly successful clones like CG258 is not the predominant dissemination vehicle, and instead HGT-related spread could be playing a more important role.Disclosures All authors: No reported disclosures.

Novel fluorinated platinum(II) complexes with pyridine-2-carboxylate ligand as potent radiosensitizer and antiviral agent

Novel Pt(II) complexes, (TFPPy)PtPic and (TFPQ)PtPic, containing fluorinated phenylpyridine or phenylquinoline with pyridine-2-carboxylate as chelating ligands were synthesized according to rational design, their therapeutical activities examined. Remarkable radiosensitization SER values were observed even in radio-resistant cell line after treated with these complexes. Furthermore, the two complexes have shown antiviral activity against DNA virus HSV-1. Comply with live cell imaging results, molecular docking have revealed the complexes forms stable hydrogen bond and hydrophobic interactions to the minor groove of target DNA double helix. These findings demonstrate the non-classical structure complexes are promising for further evaluation as a new type of prodrug radiochemotherapy and antiviral treatment.