Superexchange coupling of donor qubits in silicon

Atomic engineering in a solid-state material has the potential to functionalize the host with novel phenomena. STM-based lithographic techniques have enabled the placement of individual phosphorus atoms at selective lattice sites of silicon with atomic precision. Here, we show that by placing four phosphorus donors spaced 10-15 nm apart from their neighbours in a linear chain, it is possible to realize coherent spin coupling between the end dopants of the chain, analogous to the superexchange interaction in magnetic materials. Since phosphorus atoms are a promising building block of a silicon quantum computer, this enables spin coupling between their bound electrons beyond nearest neighbours, allowing the qubits to be spaced out by 30-45 nm. The added flexibility in architecture brought about by this long-range coupling not only reduces gate densities but can also reduce correlated noise between qubits from local noise sources that are detrimental to error correction codes. We base our calculations on a full configuration interaction technique in the atomistic tight-binding basis, solving the 4-electron problem exactly, over a domain of a million silicon atoms. Our calculations show that superexchange can be tuned electrically through gate voltages where it is less sensitive to charge noise and donor placement errors

Impact of measurement backaction on nuclear spin qubits in silicon

Phosphorus donor nuclear spins in silicon couple weakly to the environment making them promising candidates for high-fidelity qubits. The state of a donor nuclear spin qubit can be manipulated and read out using its hyperfine interaction with the electron confined by the donor potential. Here we use a master equation-based approach to investigate how the backaction from this electron-mediated measurement affects the lifetimes of single and multi-donor qubits. We analyze this process as a function of electric and magnetic fields, and hyperfine interaction strength. Apart from single nuclear spin flips, we identify an additional measurement-related mechanism, the nuclear spin flip-flop, which is specific to multi-donor qubits. Although this flip-flop mechanism reduces qubit lifetimes, we show that it can be effectively suppressed by the hyperfine Stark shift. We show that using atomic precision donor placement and engineered Stark shift, we can minimize the measurement backaction in multi-donor qubits, achieving larger nuclear spin lifetimes than single donor qubits

Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

<p>Abstract</p> <p>Background</p> <p>Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with <it>P. aeruginosa </it>by a Th17-mediated mechanism.</p> <p>Results</p> <p>Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the <it>P. aeruginosa </it>strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against <it>P. aeruginosa </it>in vitro.</p> <p>Conclusions</p> <p>Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with <it>P. aeruginosa </it>in the CF lung.</p

Inflammasome-Mediated IL-1β Production in Humans with Cystic Fibrosis

Inflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.Bronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.Hematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function

Analysis of arterial intimal hyperplasia: review and hypothesis

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it &quot;benign intimal hyperplasia&quot;. However, normal or &quot;benign &quot; intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Indotricarbocyanine dyes relevant for photodynamic therapy and their radicals: Substituent effects studied by optical and electrochemical methods

Photodynamic therapy is an effective and minimally invasive treatment method for cancer. A deeper under- standing of the photocytotoxicity mechanism of cyanine dyes is necessary for the development of more efficient photosensitizers. We combine electrochemistry, optical and ESR spectroscopy, and quantum chemical calcula- tions to study indotricarbocyanine dyes relevant for photodynamic therapy. The incorporation of 4-meso-chloride and a 3,5-o-phenylene bridge into the polymethine chain results in a hypsochromic shift of the absorption spectrum by ca. 30 nm and in a downward shift of the frontier orbitals energy levels by 0.1–0.3 eV. In addition, such substitution imparts stability to the electrogenerated radical dications of the dyes. The presence of 4-meso- chloride and a 3,5-trimethylene bridge in the polymethine chain causes the absorption spectrum to shift bath- ochromically by almost 40 nm and the HOMO–LUMO energy gap to decrease by ca. 0.1 eV. The radical dication of the dye with such substitution is particularly stable and exhibits improved electron delocalization. The radical dication of the dye with an unsubstituted polymethine chain is unstable due to its propensity to form dimers. The substituents at the nitrogen atoms are shown to have almost no influence on the optical and electrochemical properties of the indotricarbocyanine dyes. The radical dications of the dyes with an o-phenylene bridge can oxidize bromide ions, unlike the radical dications of the dyes with an unsubstituted polymethine chain or with a trimethylene bridge. The reported data can be used to develop new indotricarbocyanine dyes with desired characteristics