Accurate Hyperfine Coupling Calculations of Radiation Induced DNA Constituent Radicals Using Density Functional Theory.

Previous density functional theory (DFT) calculations of hyperfine coupling constants (HFCC) on single nucleic acid base radicals agree well with the EPR/ENDOR experiments’ values on radiation induced nucleic acid constituents radicals, except for four problem cases,1 namely the N1-deprotonated cytosine cation radical, the native guanine cation radical, the N3-deprotonated 5’-dCMP cation radical and the N7-H, O6-H protonated 5’-GMP anion. The main effort of the present work is to address these four discrepancies by using the highly parameterized density functional M05/6-2X and by including the crystalline environment’s H-bonding effects in the calculations. The geometries of the four model radicals are optimized within their single crystal environment using ONIOM technique. Then the spin density distributions and HFCCs of the radicals are examined within various scales of cluster models. The results obtained by including H-bonding environment are in strong agreement with the experimental values. The calculations show advantages of using the M05/62X functional rather than the B3LYP functional in obtaining more satisfactory HFCC results. However, the delocalization errors are encountered with both M05/6-2X and B3LYP functionals. Further development in eliminating delocalization errors in practical DFT approximations is suggested

Calculating Hyperfine Couplings in Large Ionic Crystals Containing Hundreds of QM Atoms: Subsystem DFT is the Key

We present an application of the linear scaling Frozen Density Embedding (FDE) formulation of subsystem DFT to the calculation of isotropic hyperfine coupling constants (hfccs) of atoms belonging to a guanine radical cation embedded in a guanine hydrochloride monohydrate crystal. The model systems considered range from an isolated guanine to a 15,000 atom QM/MM cluster where the QM region is comprised of 36 protonated guanine cations, 36 chlorine anions and 42 water molecules. Our calculations show that the embedding effects of the surrounding crystal cannot be reproduced neither by small model systems nor by a pure QM/MM procedure. Instead, a large QM region is needed to fully capture the complicated nature of the embedding effects in this system. The unprecedented system size for a relativistic all-electron isotropic hfccs calculation can be approached in this work because the local nature of the electronic structure of the organic crystals considered is fully captured by the FDE approach

Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration

Branched actin network supports cell migration through extracellular microenvironments. However, it is unknown how intracellular proteins adapt the elastic properties of the network to the highly varying extracellular resistance. Here we develop a three-dimensional assembling model to simulate the realistic self-assembling process of the network by encompassing intracellular proteins and their dynamic interactions. Combining this multiscale model with finite element method, we reveal that the network can not only sense the variation of extracellular resistance but also self-adapt its elastic properties through remodeling with intracellular proteins. Such resistance-adaptive elastic behaviours are versatile and essential in supporting cell migration through varying extracellular microenvironments. The bending deformation mechanism and anisotropic Poisson’s ratios determine why lamellipodia persistently evolve into sheet-like structures. Our predictions are confirmed by published experiments. The revealed self-adaptive elastic properties of the networks are also applicable to the endocytosis, phagocytosis, vesicle trafficking, intracellular pathogen transport and dendritic spine formation

Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization

BackgroundThe mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.MethodsWe collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), in situ hybridization and immunohistochemistry for MCP-1, TNF-α, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score.ResultsHE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. In situ hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-α, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, Firmicutes was significantly higher in HS than NS. At the genus level, S. aureus was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices.ConclusionMicrobiome dysbiosis, dominated by S. aureus, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management

Quantum Simulation of an Extended Fermi-Hubbard Model Using a 2D Lattice of Dopant-based Quantum Dots

The Hubbard model is one of the primary models for understanding the essential many-body physics in condensed matter systems such as Mott insulators and cuprate high-Tc superconductors. Recent advances in atomically precise fabrication in silicon using scanning tunneling microscopy (STM) have made possible atom-by-atom fabrication of single and few-dopant quantum dots and atomic-scale control of tunneling in dopant-based devices. However, the complex fabrication requirements of multi-component devices have meant that emulating two-dimensional (2D) Fermi-Hubbard physics using these systems has not been demonstrated. Here, we overcome these challenges by integrating the latest developments in atomic fabrication and demonstrate the analog quantum simulation of a 2D extended Fermi-Hubbard Hamiltonian using STM-fabricated 3x3 arrays of single/few-dopant quantum dots. We demonstrate low-temperature quantum transport and tuning of the electron ensemble using in-plane gates as efficient probes to characterize the many-body properties, such as charge addition, tunnel coupling, and the impact of disorder within the array. By controlling the array lattice constants with sub-nm precision, we demonstrate tuning of the hopping amplitude and long-range interactions and observe the finite-size analogue of a transition from Mott insulating to metallic behavior in the array. By increasing the measurement temperature, we simulate the effect of thermally activated hopping and Hubbard band formation in transport spectroscopy. We compare the analog quantum simulations with numerically simulated results to help understand the energy spectrum and resonant tunneling within the array. The results demonstrated in this study serve as a launching point for a new class of engineered artificial lattices to simulate the extended Fermi-Hubbard model of strongly correlated materials

Prevalence of Common Respiratory Viral Infections and Identification of Adenovirus in Hospitalized Adults in Harbin, China 2014 to 2017

Background: Respiratory infections pose a great challenge in global health, and the prevalence of viral infection in adult patients has been poorly understood in northeast China. Harbin is one of the major cities in northeast China, and more than half of any given year in Harbin is occupied by winter. To reveal the viral etiology and seasonality in adult patients from Harbin, a 4-year consecutive survey was conducted in Harbin, China.Methods: From January 2014 to December 2017, specimens were obtained from adult patients admitted to the Second Affiliated Hospital of Harbin Medical University with lower respiratory tract infections. Sputum samples were examined by direct immunofluorescence assays to detect seven common respiratory viruses, including influenza virus (type A and B), parainfluenza virus (type 1 to 3), respiratory syncytial virus and adenovirus. Adenovirus positive samples were seeded onto A549 cells to isolate viral strains. Phylogenetic analysis was conducted on the highly variable region of adenoviral hexon gene.Results: A total of 1,300 hospitalized adult patients with lower respiratory tract infections were enrolled, in which 189 patients (14.5%) were detected as having at least one viral infection. The co-infection rate in this study was 25.9% (49/189). The dominant viral pathogen from 2014 to 2017 was parainfluenza virus, with a detection rate of 7.2%, followed by influenza virus, respiratory syncytial virus and adenovirus. Based on the climate seasons determined by daily average temperature, the highest overall viral detection rate was detected in spring (22.0%, 52/236), followed by winter (13.4%, 109/813), autumn (11.4%, 13/114) and summer (10.9%, 15/137). Adenovirus type 3 strains with slight variations were isolated from positive cases, which were closely related to the GB strain from the United States, as well as the Harbin04B strain isolated locally.Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen. Climate seasons could be rational indicators for the seasonality analysis of airborne viral infections. Future surveillance on viral mutations would be necessary to reveal the evolutionary history of respiratory viruses

ATOMICALLY PRECISE FABRICATION AND CHARACTERIZATION OF DONOR-BASED QUANTUM DEVICES IN SILICON

Atomically precise donor-based quantum devices in silicon are a promising candidate for scalable solid-state quantum computing and analog quantum simulation. This thesis demonstrates success in fabricating state-of-the-art silicon-phosphorus (Si:P) quantum devices with atomic precision. We present critical advances towards fabricating high-fidelity qubit circuitry for scalable quantum information processing that demands unprecedented precision and reproducibility to control and characterize precisely placed donors, electrodes, and the quantum interactions between them. We present an optimized atomically precise fabrication scheme with improved process control strategies to encapsulate scanning tunneling microscope (STM)-patterned devices and technological advancements in device registration and electrical contact formation that drastically increase the yield of atomic-precision fabrication. We present an atomic-scale characterization of monolayer step edges on Si (100) surfaces using spatially resolved scanning tunneling spectroscopy and quantitatively determine the impact of step edge density of states on the local electrostatic environment. Utilizing local band bending corrections, we report a significant band gap narrowing behavior along rebonded SB step edges on a degenerately boron-doped Si substrate. We quantify and control atomic-scale dopant movement and electrical activation in silicon phosphorus (Si:P) monolayers using room-temperature grown locking layers (LL), sputter profiling simulation, and magnetotransport measurements. We explore the impact of LL growth conditions on dopant confinement and show that the dopant segregation length can be suppressed below one Si lattice constant while maintaining good epitaxy. We demonstrate weak-localization measurement as a high-resolution, high-throughput, and non-destructive method in determining the conducting layer thickness in the sub-nanometer thickness regime. Finally, we present atomic-scale control of tunnel coupling using STM-patterned Si:P single electron transistors (SET). We demonstrate the exponential scaling of tunnel coupling down to the atomic limit by utilizing the Si (100) 2×1 surface reconstruction lattice as a natural ruler with atomic-accuracy and varying the number of lattices counts in the tunnel gaps. We analyze resonant tunneling spectroscopy through atomically precise tunnel gaps as we scale the SET islands down to the few-donor quantum dot regime. Finally, by combining single/few-donor quantum dots with atomically defined single electron transistors as charge sensors, we demonstrate single electron charge sensing in few-donor quantum dots and characterize the tunnel coupling between few-donor quantum dots and precision-aligned single electron charge sensors

The Essay In The Postmodern Era

The overarching goal of this study is to suggest that the essay as a genre, although seeming to manifest the epistemological conceptions of the modern, possesses certain qualities from its origin that justify and strengthen its position in the paradigm of the postmodern condition. It is my argument that misconceptions about such qualities have led to its mistreatment by writing teachers in accordance with two dominant pedagogical approaches, formalism (current-traditionalism) and romanticism (expressivism). My argument requires a detailed examination of the political, historical and cultural reality that cultivated and nurtured the genre of the essay, and a major focus of my study is on the way Montaigne conceived of the new mode of writing as his response to the new social realities of the sixteenth century, an age marked by discoveries and inventions. To justify this approach, I consider works by composition theorists who promote an agenda of critical literacy, scholarly works on Montaigne\u27s essays, as well as various relevant works on postmodernism and literary theory. Perhaps more importantly, I look back to the chaotic, unpredictable, and skeptical mentality of the sixteenth century and attempt to draw connections between that time period and the present, as our present postmodern era is also marked by major shifts of conceptions about reality, knowledge, authority, and the self. From this framework, I indicate connections can be drawn between the two revolutionary ages, both marked by explosion of new knowledge and dissipation of authority and certainty. It is my proposition that the essay, arising from the need to question traditions and to adapt to new emerging realities, possesses qualities--explorative, skeptical, and dialogical--that procure a valid position in the ongoing questioning and challenging of the Modern by the Postmodern. Finally, I examine how essay has been and continues to be taught just for its formalistic merits and ignored for its epistemological, aesthetic, and philosophical values, an examination that serves to repudiate the wrongful relegation and dismissal of the essay and to establish a justification of not only the literary merits, but also the pedagogical values of the essay