Asymmetric synthesis of tri- and tetrasubstituted trifluoromethyl dihydropyranones from alpha-aroyloxyaldehydes via NHC redox catalysis

We thank the Royal Society for a University Research Fellowship (A.D.S.), and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement No. 279850 (A.T.D.).The asymmetric synthesis of tri- and tetrasubstituted trifluoromethyl dihydropyranones via an NHC-catalyzed redox process, introducing methyl, benzyl, and aryl substituents to the C(5) position, is presented. Their substrate-controlled derivatization into δ-lactones and cyclic hemiacetals containing stereogenic trifluoromethyl groups is also described.PostprintPeer reviewe

Franck-Condon-Broadened Angle-Resolved Photoemission Spectra Predicted in LaMnO3

The sudden photohole of least energy created in the photoemission process is a vibrationally excited state of a small polaron. Therefore the photoemission spectrum in LaMnO3 is predicted to have multiple Franck-Condon vibrational sidebands. This generates an intrinsic line broadening approximately 0.5 eV. The photoemission spectral function has two peaks whose central energies disperse with band width approximately 1.2 eV. Signatures of these phenomena are predicted to appear in angle-resolved photoemission spectra.Comment: Revtex file 4 pages and 3 figure

Polaronic Signatures in Mid-Infrared Spectra: Prediction for LaMnO3 and CaMnO3

Hole-doped LaMnO3 and electron-doped CaMnO3 form self-trapped electronic states. The spectra of these states have been calculated using a two orbital (Mn eg Jahn-Teller) model, from which the non-adiabatic optical conductivity spectra are obtained. In both cases the optical spectrum contains weight in the gap region, whose observation will indicate the self-trapped nature of the carrier states. The predicted spectra are proportional to the concentration of the doped carriers in the dilute regime, with coefficients calculated with no further model parameters.Comment: 6 pages with 3 figures imbedde

Spin versus Lattice Polaron: Prediction for Electron-Doped CaMnO3

CaMnO3 is a simple bi-partite antiferromagnet(AF) which can be continuously electron-doped up to LaMnO3. Electrons enter the doubly degenerate E_g subshell with spins aligned to the S=3/2 core of Mn^4+ (T_2g^3)$. We take the Hubbard and Hund energies to be effectively infinite. Our model Hamiltonian has two E_g orbitals per Mn atom, nearest neighbor hopping, nearest neighbor exchange coupling of the S=3/2 cores, and electron-phonon coupling of Mn orbitals to adjacent oxygen atoms. We solve this model for light doping. Electrons are confined in local ferromagnetic (FM) regions (spin polarons) where there proceeds an interesting competition between spin polarization (spin polarons) which enlarges the polaron, and lattice polarization (Jahn-Teller polarons) which makes it smaller. A symmetric 7-atom ferromagnetic cluster (Mn_7^27+) is the stable result, with net spin S=2 relative to the undoped AF. The distorted oxygen positions around the electron are predicted. The model also predicts a critical doping x_c=0.045 where the polaronic insulator becomes unstable relative to a FM metal.Comment: 9 pages with 7 embedded postscript figures and 2 table

Multi-phonon Resonant Raman Scattering Predicted in LaMnO3 from the Franck-Condon Process via Self-Trapped Excitons

Resonant behavior of the Raman process is predicted when the laser frequency is close to the orbital excitation energy of LaMnO3 at 2 eV. The incident photon creates a vibrationally excited self-trapped ``orbiton'' state from the orbitally-ordered Jahn-Teller (JT) ground state. Trapping occurs by local oxygen rearrangement. Then the Franck-Condon mechanism activates multiphonon Raman scattering. The amplitude of the $n$-phonon process is first order in the electron-phonon coupling $g$. The resonance occurs {\it via} a dipole forbidden $d$ to $d$ transition. We previously suggested that this transition (also seen in optical reflectivity) becomes allowed because of asymmetric oxygen fluctuations. Here we calculate the magnitude of the corresponding matrix element using local spin-density functional theory. This calculation agrees to better than a factor of two with our previous value extracted from experiment. This allows us to calculate the absolute value of the Raman tensor for multiphonon scattering. Observation of this effect would be a direct confirmation of the importance of the JT electron-phonon term and the presence of self-trapped orbital excitons, or ``orbitons''.Comment: 8 pages and 3 embedded figures. The earlier short version is now replaced by a more complete paper with a slightly different title. This version includes a caculation by density-functional theory of the dipole matrix element for exciting the self-trapped orbital exciton which activates the multiphonon Raman signal

Rating neighborhoods for older adult health: results from the African American Health study

<p>Abstract</p> <p>Background</p> <p>Social theories suggest that neighborhood quality affects health. Observer ratings of neighborhoods should be subjected to psychometric tests.</p> <p>Methods</p> <p>African American Health (AAH) study subjects were selected from two diverse St. Louis metropolitan catchment areas. Interviewers rated streets and block faces for 816 households. Items and a summary scale were compared across catchment areas and to the resident respondents' global neighborhood assessments.</p> <p>Results</p> <p>Individual items and the scale were strongly associated with both the catchment area and respondent assessments. Ratings based on both block faces did not improve those based on a single block face. Substantial interviewer effects were observed despite strong discriminant and concurrent validity.</p> <p>Conclusion</p> <p>Observer ratings show promise in understanding the effect of neighborhood on health outcomes. The AAH Neighborhood Assessment Scale and other rating systems should be tested further in diverse settings.</p

ActEarly: a City Collaboratory approach to early promotion of good health and wellbeing.

Economic, physical, built, cultural, learning, social and service environments have a profound effect on lifelong health. However, policy thinking about health research is dominated by the 'biomedical model' which promotes medicalisation and an emphasis on diagnosis and treatment at the expense of prevention. Prevention research has tended to focus on 'downstream' interventions that rely on individual behaviour change, frequently increasing inequalities. Preventive strategies often focus on isolated leverage points and are scattered across different settings. This paper describes a major new prevention research programme that aims to create City Collaboratory testbeds to support the identification, implementation and evaluation of upstream interventions within a whole system city setting. Prevention of physical and mental ill-health will come from the cumulative effect of multiple system-wide interventions. Rather than scatter these interventions across many settings and evaluate single outcomes, we will test their collective impact across multiple outcomes with the goal of achieving a tipping point for better health. Our focus is on early life (ActEarly) in recognition of childhood and adolescence being such critical periods for influencing lifelong health and wellbeing

Plasmids and Rickettsial Evolution: Insight from Rickettsia felis

BACKGROUND: The genome sequence of Rickettsia felis revealed a number of rickettsial genetic anomalies that likely contribute not only to a large genome size relative to other rickettsiae, but also to phenotypic oddities that have confounded the categorization of R. felis as either typhus group (TG) or spotted fever group (SFG) rickettsiae. Most intriguing was the first report from rickettsiae of a conjugative plasmid (pRF) that contains 68 putative open reading frames, several of which are predicted to encode proteins with high similarity to conjugative machinery in other plasmid-containing bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Using phylogeny estimation, we determined the mode of inheritance of pRF genes relative to conserved rickettsial chromosomal genes. Phylogenies of chromosomal genes were in agreement with other published rickettsial trees. However, phylogenies including pRF genes yielded different topologies and suggest a close relationship between pRF and ancestral group (AG) rickettsiae, including the recently completed genome of R. bellii str. RML369-C. This relatedness is further supported by the distribution of pRF genes across other rickettsiae, as 10 pRF genes (or inactive derivatives) also occur in AG (but not SFG) rickettsiae, with five of these genes characteristic of typical plasmids. Detailed characterization of pRF genes resulted in two novel findings: the identification of oriV and replication termination regions, and the likelihood that a second proposed plasmid, pRFδ, is an artifact of the original genome assembly. CONCLUSION/SIGNIFICANCE: Altogether, we propose a new rickettsial classification scheme with the addition of a fourth lineage, transitional group (TRG) rickettsiae, that is unique from TG and SFG rickettsiae and harbors genes from possible exchanges with AG rickettsiae via conjugation. We offer insight into the evolution of a plastic plasmid system in rickettsiae, including the role plasmids may have played in the acquirement of virulence traits in pathogenic strains, and the likely origin of plasmids within the rickettsial tree

Stability of Yellow Fever Virus under Recombinatory Pressure as Compared with Chikungunya Virus

Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4×106 in BHK-21 (vertebrate) cells and ∼1.05×105 in C710 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease