A Convergent, Umpoled Synthesis of 2-(1-Amidoalkyl)pyridines

A convenient, one-pot, two-component synthesis of 2-(1-amidoalkyl)pyridines is reported, based upon the substitution of suitably-activated pyridine N-oxides by azlactone nucleophiles, followed by decarboxylative azlactone ring-opening. The synthesis obviates the need for precious metal catalysts to achieve a formal enolate arylation reaction, and constitutes a formally ‘umpoled’ approach to this valuable class of bioactive structures

Three-Component Synthesis of Pyridylacetic Acid Derivatives by Arylation/Decarboxylative Substitution of Meldrum’s Acids

A convenient and simple three-component synthesis of substituted pyridylacetic acid derivatives is reported. The approach centers on the dual reactivity of Meldrum’s acid derivatives, initially as nucleophiles to perform substitution on activated pyridine-N-oxides, then as electrophiles with a range of nucleophiles to trigger ring-opening and decarboxylation

Rhodium(III)-Catalyzed C-H Activation/Annulation with Vinyl Esters as an Acetylene Equivalent

The behavior of electron-rich alkenes in rhodium-catalyzed C–H activation/annulation reactions is investigated. Vinyl acetate emerges as a convenient acetylene equivalent, facilitating the synthesis of sixteen 3,4-unsubstituted isoquinolones, as well as select heteroaryl-fused pyridones. The complementary regiochemical preferences of enol ethers versus enol esters/enamides is discusse

Assessing Centrality Without Knowing Connections

We consider the privacy-preserving computation of node influence in distributed social networks, as measured by egocentric betweenness centrality (EBC). Motivated by modern communication networks spanning multiple providers, we show for the first time how multiple mutually-distrusting parties can successfully compute node EBC while revealing only differentially-private information about their internal network connections. A theoretical utility analysis upper bounds a primary source of private EBC error---private release of ego networks---with high probability. Empirical results demonstrate practical applicability with a low 1.07 relative error achievable at strong privacy budget $\epsilon=0.1$ on a Facebook graph, and insignificant performance degradation as the number of network provider parties grows.Comment: Full report of paper appearing in PAKDD202

Synthesis and Evaluation of the Performance of a Small Molecule Library Based on Diverse Tropane-Related Scaffolds

A unified synthetic approach was developed that enabled the synthesis of diverse tropane-related scaffolds. The key intermediates that were exploited were cycloadducts formed by reaction between 3-hydroxy-pyridinium salts and vinyl sulfones or sulfonamides. The diverse tropane-related scaffolds were formed by addition of substituents to, cyclisation reactions of, and fusion of additional ring(s) to the key bicyclic intermediates. A set of 53 screening compounds was designed, synthesised and evaluated in order to determine the biological relevance of the scaffolds accessible using the synthetic approach. Two inhibitors of Hedgehog signalling, and four compounds with weak activity against the parasite P. falciparum, were discovered. Three of the active compounds may be considered to be indotropane or pyrrotropane pseudo natural products in which a tropane is fused with a fragment from another natural product class. It was concluded that the unified synthetic approach had yielded diverse scaffolds suitable for the design of performance-diverse screening libraries

Enterobius vermicularis in the male urinary tract: a case report

Enterobius vermicularis is an intestinal nematode of humans. Adults usually have low worm burdens and are asymptomatic. Ectopic infections in the pelvic area or urinary tract rarely occur in women. We report a case of the patient with mild voiding difficulties such as urgency, frequency, nocturia, dysuria, mild low back pain or perineal discomfort. The patient's prostatic secretions showed a large number of inflammatory cells and several eggs. The size and the shape of the eggs identified them as a group of E. vermicularis. On examination we found a soft palpable material which was 5 mm diameter in size and spherical shape. Palpation gave the impression of a tissue than a stone. An incision was performed and a 4 mm long living worm was found. The microscopic examination identified the worm as E- vermicularis. It is an extremely rare manifestation of enterobius vermicularis infection since an intestinal-breeding worm is rarely found in the male genital tract

Synthesis of spirocyclic 1,2-diamines by dearomatising intramolecular diamination of phenols

The stereocontrolled synthesis of complex spirotricyclic systems containing an embedded syn-1,2-diaminocyclohexane unit is reported, based upon a dearomatising oxidation of phenols bearing pendant ureas capable of acting as double nucleophiles. This complexity-generating transformation yields products with rich functionality suitable for application in the synthesis of potentially bioactive compounds

Modular Synthesis of Bicyclic Twisted Amides and Anilines

Bridged amides and anilines display interesting properties owing to perturbation of conjugation of the nitrogen lone-pair with the adjacent π-system. A convergent approach to diazabicyclic scaffolds which contain either twisted amides or anilines is described, based on the photocatalysed hydroamination of cyclic enecarbamates and subsequent cyclisation. The modular nature of the synthesis allows for variation of the degree of ‘twist’ and hence the properties of the amides and anilines

Estimating magnetic filling factors from Zeeman-Doppler magnetograms

This is the author accepted manuscript. The final version is available from American Astronomical Society via the DOI in this record.Low-mass stars are known to have magnetic fields that are believed to be of dynamo origin. Two complementary techniques are principally used to characterise them. Zeeman-Doppler imaging (ZDI) can determine the geometry of the large-scale magnetic field while Zeeman broadening can assess the total unsigned flux including that associated with small-scale structures such as spots. In this work, we study a sample of stars that have been previously mapped with ZDI. We show that the average unsigned magnetic flux follows an activity-rotation relation separating into saturated and unsaturated regimes. We also compare the average photospheric magnetic flux recovered by ZDI, hBV i, with that recovered by Zeeman broadening studies, hBI i. In line with previous studies, hBV i ranges from a few % to ∼20% of hBI i. We show that a power law relationship between hBV i and hBI i exists and that ZDI recovers a larger fraction of the magnetic flux in more active stars. Using this relation, we improve on previous attempts to estimate filling factors, i.e. the fraction of the stellar surface covered with magnetic field, for stars mapped only with ZDI. Our estimated filling factors follow the well-known activity-rotation relation which is in agreement with filling factors obtained directly from Zeeman broadening studies. We discuss the possible implications of these results for flux tube expansion above the stellar surface and stellar wind models.European CommissionAustrian Space Application Programm

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis