Efforts towards the total synthesis of (+)-sorangicin A

Efforts towards (+)-sorangicin A, a previously unprepared antibiotic macrolide, are reported. A modular approach which investigates several coupling strategies for the union of three core cyclic ether fragments was utilized. The bicyclic ether and tetrahydropyran moieties were constructed utilizing a ringclosing/epoxide opening strategy while the dihydropyran subunit relied on a ring-closing metathesis for the formation of the heterocycle. The three core synthetic fragments were elaborated to various synthetic intermediates and several coupling strategies were evaluated

A Dust Twin of Cas A: Cool Dust and 21-micron Silicate Dust Feature in the Supernova Remnant G54.1+0.3

We present infrared (IR) and submillimeter observations of the Crab-like supernova remnant (SNR) G54.1+0.3 including 350 micron (SHARC-II), 870 micron (LABOCA), 70, 100, 160, 250, 350, 500 micron (Herschel) and 3-40 micron (Spitzer). We detect dust features at 9, 11 and 21 micron and a long wavelength continuum dust component. The 21 micron dust coincides with [Ar II] ejecta emission, and the feature is remarkably similar to that in Cas A. The IRAC 8 micron image including Ar ejecta is distributed in a shell-like morphology which is coincident with dust features, suggesting that dust has formed in the ejecta. We create a cold dust map that shows excess emission in the northwestern shell. We fit the spectral energy distribution of the SNR using the continuous distributions of ellipsoidal (CDE) grain model of pre-solar grain SiO2 that reproduces the 21 and 9 micron dust features and discuss grains of SiC and PAH that may be responsible for the 10-13 micron dust features. To reproduce the long-wavelength continuum, we explore models consisting of different grains including Mg2SiO4, MgSiO3, Al2O3, FeS, carbon, and Fe3O4. We tested a model with a temperature-dependent silicate absorption coefficient. We detect cold dust (27-44 K) in the remnant, making this the fourth such SNR with freshly-formed dust. The total dust mass in the SNR ranges from 0.08-0.9 Msun depending on the grain composition, which is comparable to predicted masses from theoretical models. Our estimated dust masses are consistent with the idea that SNe are a significant source of dust in the early Universe.Comment: MNRAS: accepted on June 28, 2018 and published on July 4, 201

Formal Synthesis of (+)-Sorangicin A

The formal synthesis of (+)-sorangicin A was completed by two independent routes. Both approaches feature a cross metathesis reaction to form the C29-C30 bond to arrive at the bicyclic ether/tetrahydropyran fragment. Formation of the C15-C16 olefin to unite the dihydropyran fragment with the rest of the molecule was achieved by either a cross metathesis reaction or a Julia-Kocienski olefination

Open-target sparse sensing of biological agents using DNA microarray

Background Current biosensors are designed to target and react to specific nucleic acid sequences or structural epitopes. These 'target-specific' platforms require creation of new physical capture reagents when new organisms are targeted. An 'open-target' approach to DNA microarray biosensing is proposed and substantiated using laboratory generated data. The microarray consisted of 12,900 25 bp oligonucleotide capture probes derived from a statistical model trained on randomly selected genomic segments of pathogenic prokaryotic organisms. Open-target detection of organisms was accomplished using a reference library of hybridization patterns for three test organisms whose DNA sequences were not included in the design of the microarray probes. Results A multivariate mathematical model based on the partial least squares regression (PLSR) was developed to detect the presence of three test organisms in mixed samples. When all 12,900 probes were used, the model correctly detected the signature of three test organisms in all mixed samples (mean(R2)) = 0.76, CI = 0.95), with a 6% false positive rate. A sampling algorithm was then developed to sparsely sample the probe space for a minimal number of probes required to capture the hybridization imprints of the test organisms. The PLSR detection model was capable of correctly identifying the presence of the three test organisms in all mixed samples using only 47 probes (mean(R2)) = 0.77, CI = 0.95) with nearly 100% specificity. Conclusions We conceived an 'open-target' approach to biosensing, and hypothesized that a relatively small, non-specifically designed, DNA microarray is capable of identifying the presence of multiple organisms in mixed samples. Coupled with a mathematical model applied to laboratory generated data, and sparse sampling of capture probes, the prototype microarray platform was able to capture the signature of each organism in all mixed samples with high sensitivity and specificity. It was demonstrated that this new approach to biosensing closely follows the principles of sparse sensing.Mitre Corporatio

IllustrisTNG and S2COSMOS: possible conflicts in the evolution of neutral gas and dust

We investigate the evolution in galactic dust mass over cosmic time through (i) empirically derived dust masses using stacked submillimetre fluxes at 850 μm in the COSMOS field and (ii) dust masses derived using a robust post-processing method on the results from the cosmological hydrodynamical simulation IllustrisTNG. We effectively perform a ‘self-calibration’ of the dust mass absorption coefficient by forcing the model and observations to agree at low redshift and then compare the evolution shown by the observations with that predicted by the model. We create dust mass functions (DMFs) based on the IllustrisTNG simulations from 0 < z < 0.5 and compare these with previously observed DMFs. We find a lack of evolution in the DMFs derived from the simulations, in conflict with the rapid evolution seen in empirically derived estimates of the low-redshift DMF. Furthermore, we observe a strong evolution in the observed mean ratio of dust mass to stellar mass of galaxies over the redshift range 0 < z < 5, whereas the corresponding dust masses from IllustrisTNG show relatively little evolution, even after splitting the sample into satellites and centrals. The large discrepancy between the strong observed evolution and the weak evolution predicted by IllustrisTNG plus post-processing may be explained by either strong cosmic evolution in the properties of the dust grains or limitations in the model. In the latter case, the limitation may be connected to previous claims that the neutral gas content of galaxies does not evolve fast enough in IllustrisTNG

Metal factories in the early universe

We have estimated the mass of metals in the molecular gas in 13 dusty star-forming galaxies at z ∼ 4 in which the gas, based on previous observations, lies in a cold rotating disk. We estimated the metal masses using either the submillimetre line or continuum emission from three tracers of the overall metal content - carbon atoms, carbon monoxide molecules and dust grains - using the first simultaneous calibration of all three tracers. We obtain very similar mass estimates from the different tracers, which are similar to the entire metal content of a present-day massive early-type galaxy. We used the dynamical masses of these galaxies to estimate an upper limit on the mass of the molecular gas in each galaxy, allowing us to estimate a lower limit on the metal abundance of the gas, finding values for many of the galaxies well above the solar value. We show that the high metal masses and metal abundances are what is expected shortly after the formation of a galaxy for a top-heavy IMF. We suggest a scenario for galaxy evolution in which massive galaxies reach a high metal abundance during their formation phase, which is then gradually reduced by dry mergers with lower mass galaxies. We show that the metals in the outflows from high-redshift dusty star-forming galaxies can quantitatively explain the long-standing puzzle that such a large fraction of the metals in galaxy clusters (≃0.75) is in the intracluster gas rather than in the galaxies themselves

Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance

Background: Treatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the choice and efficacy of a selected targeted therapeutic, and hence the objective of this study was to analyze discordance in EGFR status in patients with lung cancer brain metastasis (LCBM). Methods: Using PRISMA guidelines, a systematic review was performed of series in the Medline database of biopsied or resected LCBM published before May, 2020. Key words included “lung cancer” and “brain metastasis” combined with “epidermal growth factor receptor/EGFR,” and “receptor conversion/discordance or concordance.” Weighted random effects models were used to calculate pooled estimates. Results: We identified 501 patients from 19 full-text articles for inclusion in this study. All patients underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. On primary/LCBM comparison, the weighted pooled estimate for overall EGFR receptor discordance was 10% (95% CI 5–17%). The weighted effects model estimated a gain of an EGFR mutation in a brain metastases in patients with negative primary tumors was 7% (95% CI 4–12%). Alternatively, the weighted effects model estimate of loss of an EGFR mutation in patients with detected mutations in the primary tumor was also 7% (95% CI 4–10%). KRAS testing was also performed on both primary tumors and LCBM in a subset of 148 patients. The weighted effects estimate of KRAS-mutation discordance among LCBM compared to primary tumors was 13% (95% CI 5–27%). The weighted effects estimated of KRAS gain and loss in LCBM was 10% (95% CI 6–18%) and 8% (95% CI 4–15%), respectively. Meta-regression analysis did not find any association with any factors that could be associated with discordances. Conclusions: EGFR and KRAS mutation status discordance between primary tumor and LCBM occurs in approximately 10% and 13% of patients, respectively. Evaluation of LCBM receptor status is key to biomarker-driven targeted therapy for intracranial disease and awareness of subtype switching is critical for those patients treated with systemic therapy alone for intracranial disease

Race and Ethnicity, Obesity, Metabolic Health, and Risk of Cardiovascular Disease in Postmenopausal Women

Background It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups. Methods and Results We identified 14 364 postmenopausal women from the Women\u27s Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m2) as normal weight (body mass index 18.5 to P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity. Conclusions Metabolic abnormalities appeared to convey more cardiovascular risk among black women