Bis[μ-bis(diphenylphosphino)methane-К²P:P’]bis[(saccharinato-КN)- palladium(I)] dichloromethane solvate

The dimeric palladium(I) saccharinate complex [Pd₂(sac)₂(dppm)₂], has been characterized as its di¬chloro¬methane solvate, i.e. [Pd₂(C₇H₄NO₃S)₂(C₂₅H₂₂P₂)₂]•CH₂Cl₂. The complex features a Pd—Pd bond bridged by two dppm ligands, with the saccharinate ligands N-bonded trans to the Pd—Pd bond

Progress toward the Enantioselective Synthesis of Curcusones A–D via a Divinylcyclopropane Rearrangement Strategy

We report our iterative efforts toward the divergent total syntheses of curcusones A–D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment

Experience with key indicator cases among otolaryngology residents

Objective To describe the resident experience with respect to key indicator cases for each year of training. Study Design Multi‐institution, cross‐sectional assessment. Methods Using an electronic survey, current otolaryngology residents were solicited to complete a survey regarding their experiences with the key indicator cases to that point. The survey was sent to this cohort in the winter of 2017–2018. Results Three hundred and three residents responded, with 293 completing the survey. Twenty‐three percent were PGY1, 19% PGY2, 21% PGY3, 18% PGY4, and 19% PGY5 or higher. The majority of residents progress from resident assistant as a PGY2, to resident surgeon as a PGY3 and self‐assessed competent surgeon as a PGY4 for the majority of the key indicator cases. Less than 50% of the surveyed PGY5 residents had reached independent practice in all the key indicator cases, with stapedectomy (16%), rhinoplasty (18%), and paramedian forehead flap (14.5%) being the cases least frequently performed independently. Ninety‐five percent of the respondent residents felt their program provided adequate training, but 20% of the respondents were either unsure or believed that they would be unable to perform all the key indicator cases by the completion of their training. Conclusions The majority of otolaryngology residents feel confident in their training, but experience with certain cases lags behind and may not currently be taught as resident level cases. These findings raise the question of whether the current key indicator cases are the best option for assessing breadth and depth of residency training. Level of Evidence N

Analysis of margin classification systems for assessing the risk of local recurrence after soft tissue sarcoma resection

Purpose: To compare the ability of margin classification systems to determine local recurrence (LR) risk after soft tissue sarcoma (STS) resection. Methods: Two thousand two hundred seventeen patients with nonmetastatic extremity and truncal STS treated with surgical resection and multidisciplinary consideration of perioperative radiotherapy were retrospectively reviewed. Margins were coded by residual tumor (R) classification (in which microscopic tumor at inked margin defines R1), the R+1mm classification (in which microscopic tumor within 1 mm of ink defines R1), and the Toronto Margin Context Classification (TMCC; in which positive margins are separated into planned close but positive at critical structures, positive after whoops re-excision, and inadvertent positive margins). Multivariate competing risk regression models were created. Results: By R classification, LR rates at 10-year follow-up were 8%, 21%, and 44% in R0, R1, and R2, respectively. R+1mm classification resulted in increased R1 margins (726 v 278, P < .001), but led to decreased LR for R1 margins without changing R0 LR; for R0, the 10-year LR rate was 8% (range, 7% to 10%); for R1, the 10-year LR rate was 12% (10% to 15%) . The TMCC also showed various LR rates among its tiers (P < .001). LR rates for positive margins on critical structures were not different from R0 at 10 years (11% v 8%, P = .18), whereas inadvertent positive margins had high LR (5-year, 28% [95% CI, 19% to 37%]; 10-year, 35% [95% CI, 25% to 46%]; P < .001). Conclusion: The R classification identified three distinct risk levels for LR in STS. An R+1mm classification reduced LR differences between R1 and R0, suggesting that a negative but < 1-mm margin may be adequate with multidisciplinary treatment. The TMCC provides additional stratification of positive margins that may aid in surgical planning and patient education

A short hairpin RNA screen of interferon-stimulated genes identifies a novel negative regulator of the cellular antiviral response

ABSTRACT The type I interferon (IFN) signaling pathway restricts infection of many divergent families of RNA and DNA viruses by inducing hundreds of IFN-stimulated genes (ISGs), some of which have direct antiviral activity. We screened 813 short hairpin RNA (shRNA) constructs targeting 245 human ISGs using a flow cytometry approach to identify genes that modulated infection of West Nile virus (WNV) in IFN-β-treated human cells. Thirty ISGs with inhibitory effects against WNV were identified, including several novel genes that had antiviral activity against related and unrelated positive-strand RNA viruses. We also defined one ISG, activating signal cointegrator complex 3 (ASCC3), which functioned as a negative regulator of the host defense response. Silencing of ASCC3 resulted in upregulation of multiple antiviral ISGs, which correlated with inhibition of infection of several positive-strand RNA viruses. Reciprocally, ectopic expression of human ASCC3 or mouse Ascc3 resulted in downregulation of ISGs and increased viral infection. Mechanism-of-action and RNA sequencing studies revealed that ASCC3 functions to modulate ISG expression in an IRF-3- and IRF-7-dependent manner. Compared to prior ectopic ISG expression studies, our shRNA screen identified novel ISGs that restrict infection of WNV and other viruses and defined a new counterregulatory ISG, ASCC3, which tempers cell-intrinsic immunity. IMPORTANCE West Nile virus (WNV) is a mosquito-transmitted virus that continues to pose a threat to public health. Innate immune responses, especially those downstream of type I interferon (IFN) signaling, are critical for controlling virus infection and spread. We performed a genetic screen using a gene silencing approach and identified 30 interferon-stimulated genes (ISGs) that contributed to the host antiviral response against WNV. As part of this screen, we also identified a novel negative regulatory protein, ASCC3, which dampens expression of ISGs, including those with antiviral or proinflammatory activity. In summary, our studies define a series of heretofore-uncharacterized ISGs with antiviral effects against multiple viruses or counterregulatory effects that temper IFN signaling and likely minimize immune-mediated pathology

The DEEP2 Galaxy Redshift Survey: Clustering of Groups and Group Galaxies at z~1

We study the clustering properties of groups and of galaxies in groups in the DEEP2 Galaxy Redshift Survey dataset at z~1. Four clustering measures are presented: 1) the group correlation function for 460 groups with estimated velocity dispersions of sigma>200 km/s, 2) the galaxy correlation for the full galaxy sample, using a flux-limited sample of 9800 objects between 0.7<z<1.0, 3) the galaxy correlation for galaxies in groups, and 4) the group-galaxy cross-correlation function. Using the observed number density and clustering amplitude of the groups, the estimated minimum group dark matter halo mass is M_min~6 10^12 h^-1 M_Sun for a flat LCDM cosmology. Groups are more clustered than galaxies, with a relative bias of b=1.7 +/-0.04 on scales r_p=0.5-15 Mpc/h. Galaxies in groups are also more clustered than the full galaxy sample, with a scale-dependent relative bias which falls from b~2.5 +/-0.3 at r_p=0.1 Mpc/h to b~1 +/-0.5 at r_p=10 Mpc/h. The correlation functions for all galaxies and galaxies in groups can be fit by a power-law on scales r_p=0.05-20 Mpc/h. We empirically measure the contribution to the projected correlation function for galaxies in groups from a `one-halo' term and a `two-halo' term by counting pairs of galaxies in the same or in different groups. The projected cross-correlation between shows that red galaxies are more centrally concentrated in groups than blue galaxies at z~1. DEEP2 galaxies in groups appear to have a shallower radial distribution than that of mock galaxy catalogs made from N-body simulations, which assume a central galaxy surrounded by satellite galaxies with an NFW profile. We show that the clustering of galaxies in groups can be used to place tighter constraints on the halo model than can be gained from using the usual galaxy correlation function alone.Comment: 22 pages, 12 figures, in emulateapj format, accepted to ApJ, minor changes made to match published versio

Remotely-sensed imagery vs. eye-level photography: Evaluating associations among measurements of tree cover density

AbstractThe easy availability and widespread use of remotely-sensed imagery, especially Google Earth satellite imagery, makes it simple for urban forestry professionals to assess a site and measure tree cover density without visiting the site. Remotely-sensed tree cover density has become the dominant criterion for urban forestry regulations in many countries, but it is unclear how much such measures match the eye-level tree cover density that people experience; or the information gained through site visits, eye-level photography, or from consulting with citizens. To address this uncertainty, we assessed associations among two remotely-sensed and three eye-level tree cover density measures for 140 community street sites across the Midwestern United States with low, medium, or high tree cover coverage by using linear regression analysis. We found significant associations among the two remotely-sensed measures and the three eye-level measures across the three levels of tree cover. The associations between any pair of remotely-sensed and eye-level measures, however, diminish dramatically as canopy cover increased. At high levels of canopy cover, all associations between the remotely-sensed measures and the eye-level measures became statistically insignificant. These findings suggest that measures from remotely-sensed imagery fail to represent the amount of tree cover people perceive at eye-level when canopy cover is medium or high at the site scale. Therefore, the current urban forestry planning regulations, which rely heavily on remotely-sensed tree cover density measurements, need to be revised. We suggest strategic spots where eye-level measures of tree cover density should be emphasized

Controlled surface-associated delivery of genes and oligonucleotides

A system and methods for controlled gene delivery comprising condensed nucleic acids complexed with polylinkers, wherein the complexes are covalently and/or noncovalently bound to the surface of a substrate capable of supporting cell adhesion. The gene delivery system achieves temporal and spatial control of nucleic acid delivery to a target cell or cells through control of complex density on the surface of the support substrate, and reversibility of the attachment of the polylinker to the support substrate. The system and method of the invention can be used to create spatial patterns of gene expression, and in tissue engineering, high throughput screening, and gene therapy applications. What is claimed is: 1. A method for increasing transgene expression, comprising making a controlled nucleic acid delivery system, said system comprising forming nucleic acid polylinker complexes capable of being delivered to cells cultured on a support substrate, wherein said complexes are formed prior to being covalently or non-covalently immobilized to the surface of a support substrate, and wherein said method comprises: a) contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex, said complex being formed prior to attachment to a support substrate; and b) immobilizing the nucleic acid-polylinker complex to a support substrate; and wherein said cells are added to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate. 2. The method of claim 1, further comprising modification of the support substrate with serum prior to addition of the nucleic acid-polylinker complex, and wherein said modification allows for an increase in transgene expression. 3. The method of claim 1, wherein the extent of transgene expression is dependent upon substrate modification and complex formation. 4. The method of claim 1, wherein said nucleic acid polylinker complexes are polyplexes or lipoplexes. 5. The method of claim 1, wherein said support substrate is polystyrene, gold, hyaluronic acid collagen hydrogels or polylactide-co-glycolide (PLG). 6. The method of claim 2, wherein said substrate modification is made by treatment with serum. 7. The method of claim 1, wherein delivery of the nucleic acid-polylinker complexes to cells occurs from a polystyrene surface treated with serum, and wherein said delivery results in similar or greater percentage of transfected cells relative to bolus delivery. 8. The method of claim 1, said method further comprising release of the nucleic acid from the nucleic acid-polylinker complexes, wherein said release is maximized when the support substrate is treated with serum. 9. A method for increasing transgene expression, comprising making a controlled nucleic acid delivery system, said system comprising forming nucleic acid polylinker complexes capable of being delivered to cells cultured on a support substrate, wherein said complexes are covalently or non-covalently immobilized to the surface of a support substrate, and wherein said method comprises: a) contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex; b) immobilizing the nucleic acid-polylinker complex to a support substrate; and c) adding cells to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein the release of nucleic acid from the nucleic acid-polylinker complexes is further enhanced when the support substrate containing the complexes is treated with serum or is incubated in conditioned medium. 10. The method of claim 2, wherein the delivery of the nucleic acid-polylinker complexes to cells from a serum-modified support substrate results in higher cellular association of the nucleic acid-polylinker complexes with the support substrate. 11. A method for increasing transgene expression, comprising the steps of: a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex, wherein said complex is formed prior to addition to a support substrate; b) immobilizing the nucleic acid-polylinker complex to a support substrate; wherein said immobilizing is accomplished by covalent or non-covalent means, and c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate. 12. The method of claim 11, wherein said support substrate comprises a biodegradable or non-biodegradable material. 13. The method of either one of claim 1 or 11, wherein said complexes are formed prior to attachment to the solid support substrate. 14. The method of claim 12, wherein said biodegradable material is a hydrogel and said non-biodegradable material is polystyrene or gold. 15. The method of claim 12, wherein said hydrogel comprises a mixture of hyaluronic acid and collagen. 16. A method for increasing transgene expression, wherein said method promotes transfection of primary cells, comprising the steps of: a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex; b) immobilizing the nucleic acid-polylinker complex to a support substrate; wherein said immobilizing is accomplished by covalent or non-covalent means, and c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein the biodegradable material is a hydrogel and the non-biodegradable material is polystyrene or gold, and wherein the hvdrogel comprises a mixture of hyaluronic acid and collagen. 17. The method of either one of claim 1 or 11, wherein said nucleic acid polylinker complexes are immobilized to the support substrate using biotin and avidin, or an avidin derivative, or by non-specific adsorption. 18. The method of claim 17, wherein said avidin derivative is streptavidin or neutravidin. 19. The method of any one of claim 11–15, wherein the method further comprises controlling the size of the nucleic acid polylinker complex by regulating the salt content during complex formation. 20. The method of claim 19, wherein controlling the size of said complex formation is accomplished by the presence or absence of salt during the formation of the complexes, wherein the forming of large diameter complexes in the presence of salt results in increased transgene expression, and wherein the forming of small diameter complexes in the absence of salt results in a greater percentage of cells being transfected. 21. The method of claim 19, wherein the salt is sodium chloride. 22. A method for increasing transgene expression, comprising the steps of: a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex; b) immobilizing the nucleic acid-polylinker complex to a support substrate; wherein said immobilizing is accomplished by covalent or non-covalent means, and c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein said method further comprises release of the nucleic acid from the substrate, wherein the release is optimized by using conditioned medium. 23. The method of claim 11, wherein said method further comprises biotinylation of said complex to enhance release of said complex from said substrate. 24. The method of either of claim 1 or 11, wherein the nucleic acid is DNA, RNA or an oligonucleotide. 25. The method of claim 24, wherein said oligonucleotide is an antisense oligonucleotide or a catalytic RNA capable of interfering with the expression of a gene. 26. The controlled nucleic acid delivery system of either of claim 1 or 11, wherein the polylinker is a cationic polymer, cationic lipid, cationic protein, or cationic peptide