Microwave-assisted Bohlmann–Rahtz synthesis of highly-substituted 2-aminonicotinates

Microwave irradiation of 2-carbethoxyacetamidine and an ethynyl ketone under acidic or basic conditions in ethanol at 150 °C for 1.5 h facilitated Bohlmann-Rahtz pyridine synthesis to give highly-substituted ethyl 2 aminonicotinates with total regiocontrol and in reasonable to excellent yield, following purification by immobiliza tion upon an acidic resin

Queer Touch Between Holy Women: Julian of Norwich, Margery Kempe, Birgitta of Sweden, and the Visitation

Under embargo until: 2021-12-17This essay takes a new approach to the well-known meeting between two late-medieval English visionary women, Margery Kempe and the anchoress Julian of Norwich, as described in The Book of Margery Kempe. In this analysis their conversation subtly evokes a long history of women concentrating their subversive power through intimate, spiritual exchange, a history reaching back to the Biblical Visitation scene and expressed in its medieval artistic and literary instantiations. A queer reading illuminates the way that such female same-sex relationships challenge patriarchal systems by offering a privileged access to God outside clerical supervision. By examining Margery and Julian’s encounter, Luke’s Visitation passage, its depiction in a late-medieval Book of Hours, and comparing two different Middle English translations of a Visitation vision in Birgitta of Sweden’s Revelations, the full transgressive effect of queer touch between women—or even its unspoken possibility—emerges.acceptedVersio

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology

OBJECTIVES: - To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. METHODS: - The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. RESULTS: - Twenty-one guideline statements were established. CONCLUSIONS: - Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented

Molecular Biomarkers for the Evaluation of Colorectal Cancer

Objectives: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens

Diabetes and pregnancy:national trends over a 15 year period

Aims/hypothesis: We aimed to examine time trends in national perinatal outcomes in pregnancies complicated by pre-existing type 1 or type 2 diabetes. Methods: We analysed episode-level data on all obstetric inpatient delivery events (live or stillbirth) between 1 April 1998 and 31 March 2013 (n = 813,921) using the Scottish Morbidity Record (SMR02). Pregnancies to mothers with type 1 (n = 3229) and type 2 (n = 1452) diabetes were identified from the national diabetes database (Scottish Care Information-Diabetes), and perinatal outcomes were compared among women with type 1 diabetes, type 2 diabetes and those without diabetes. Results: The number of pregnancies complicated by diabetes increased significantly, by 44% in type 1 diabetes and 90% in type 2 diabetes, across the 15 years examined, to rates of 1 in 210 and 1 in 504 deliveries, respectively. Compared with women without diabetes, delivery occurred 2.6 weeks earlier (type 1 diabetes 36.7 ± 2.3 weeks) and 2 weeks earlier (type 2 diabetes 37.3 ± 2.4 weeks), respectively, showing significant reductions for both type 1 (from 36.7 weeks to 36.4 weeks, p = 0.03) and type 2 (from 38.0 weeks to 37.2 weeks, p < 0.001) diabetes across the time period. The proportions of preterm delivery were markedly increased in women with diabetes (35.3% type 1 diabetes, 21.8% type 2 diabetes, 6.1% without diabetes; p < 0.0001), and these proportions increased with time for both groups (p < 0.005). Proportions of elective Caesarean sections (29.4% type 1 diabetes, 30.5% type 2 diabetes, 9.6% without diabetes) and emergency Caesarean sections (38.3% type 1 diabetes, 29.1% type 2 diabetes, 14.6% without diabetes) were greatly increased in women with diabetes and increased over time except for stable rates of emergency Caesarean section in type 1 diabetes. Gestational age-, sex- and parity-adjusted z score for birthweight (1.33 ± 1.34; p < 0.001) were higher in type 1 diabetes and increased over time from 1.22 to 1.47 (p < 0.001). Birthweight was also increased in type 2 diabetes (0.94 ± 1.34; p < 0.001) but did not alter with time. There were 65 perinatal deaths in offspring of mothers with type 1 diabetes and 39 to mothers with type 2 diabetes, representing perinatal mortality rates of 20.1 (95% CI 14.7, 24.3) and 26.9 (16.7, 32.9) per 1000 births, respectively, and rates 3.1 and 4.2 times, respectively, those observed in the non-diabetic population (p < 0.001). Stillbirth rates in type 1 and type 2 diabetes were 4.0-fold and 5.1-fold that in the non-diabetic population (p < 0.001). Perinatal mortality and stillbirth rates showed no significant fall over time despite small falls in the rates for the non-diabetic population. Conclusions/interpretation: Women with diabetes are receiving increased intervention in pregnancy (earlier delivery, increased Caesarean section rates), but despite this, higher birthweights are being recorded. Improvements in rates of stillbirth seen in the general population are not being reflected in changes in stillbirth or perinatal mortality in our population with diabetes

The SDSS-V Black Hole Mapper Reverberation Mapping Project: Unusual Broad-Line Variability in a Luminous Quasar

We present a high-cadence multi-epoch analysis of dramatic variability of three broad emission lines (MgII, H$\beta$, and H$\alpha$) in the spectra of the luminous quasar ($\lambda L_{\lambda}$(5100\r{A}) = $4.7 \times 10^{44}$ erg s$^{-1}$) SDSS J141041.25+531849.0 at $z = 0.359$ with 127 spectroscopic epochs over 9 years of monitoring (2013-2022). We observe anti-correlations between the broad emission-line widths and flux in all three emission lines, indicating that all three broad emission lines "breathe" in response to stochastic continuum variations. We also observe dramatic radial velocity shifts in all three broad emission lines, ranging from $\Delta{v}$ $\sim$400 km s$^{-1}$ to $\sim$800 km s$^{-1}$, that vary over the course of the monitoring period. Our preferred explanation for the broad-line variability is complex kinematics in the broad-line region gas. We suggest a model for the broad-line variability that includes a combination of gas inflow with a radial gradient, an azimuthal asymmetry (e.g., a hot spot), superimposed on the stochastic flux-driven changes to the optimal emission region ("line breathing"). Similar instances of line-profile variability due to complex gas kinematics around quasars are likely to represent an important source of false positives in radial velocity searches for binary black holes, which typically lack the kind of high-cadence data we analyze here. The long-duration, wide-field, and many-epoch spectroscopic monitoring of SDSS-V BHM-RM provides an excellent opportunity for identifying and characterizing broad emission-line variability, and the inferred nature of the inner gas environment, of luminous quasars

A Transient “Changing-look” Active Galactic Nucleus Resolved on Month Timescales from First-year Sloan Digital Sky Survey V Data

We report the discovery of a new “changing-look” active galactic nucleus (CLAGN) event, in the quasar SDSS J162829.17+432948.5 at z = 0.2603, identified through repeat spectroscopy from the fifth Sloan Digital Sky Survey (SDSS-V). Optical photometry taken during 2020-2021 shows a dramatic dimming of Δg ≈ 1 mag, followed by a rapid recovery on a timescale of several months, with the ≲2 month period of rebrightening captured in new SDSS-V and Las Cumbres Observatory spectroscopy. This is one of the fastest CLAGN transitions observed to date. Archival observations suggest that the object experienced a much more gradual dimming over the period of 2011-2013. Our spectroscopy shows that the photometric changes were accompanied by dramatic variations in the quasar-like continuum and broad-line emission. The excellent agreement between the pre- and postdip photometric and spectroscopic appearances of the source, as well as the fact that the dimmest spectra can be reproduced by applying a single extinction law to the brighter spectral states, favor a variable line-of-sight obscuration as the driver of the observed transitions. Such an interpretation faces several theoretical challenges, and thus an alternative accretion-driven scenario cannot be excluded. The recent events observed in this quasar highlight the importance of spectroscopic monitoring of large active galactic nucleus samples on weeks-to-months timescales, which the SDSS-V is designed to achieve

A Transient "Changing-look'' Active Galactic Nucleus Resolved on Month Timescales from First-year Sloan Digital Sky Survey V Data

We report the discovery of a new ``changing-look'' active galactic nucleus (CLAGN) event, in the quasar SDSS J162829.17+432948.5 at z=0.2603, identified through repeat spectroscopy from the fifth Sloan Digital Sky Survey (SDSS-V). Optical photometry taken during 2020--2021 shows a dramatic dimming of ${\Delta}$g${\approx}$1 mag, followed by a rapid recovery on a timescale of several months, with the ${\lesssim}$2 month period of rebrightening captured in new SDSS-V and Las Cumbres Observatory spectroscopy. This is one of the fastest CLAGN transitions observed to date. Archival observations suggest that the object experienced a much more gradual dimming over the period of 2011--2013. Our spectroscopy shows that the photometric changes were accompanied by dramatic variations in the quasar-like continuum and broad-line emission. The excellent agreement between the pre- and postdip photometric and spectroscopic appearances of the source, as well as the fact that the dimmest spectra can be reproduced by applying a single extinction law to the brighter spectral states, favor a variable line-of-sight obscuration as the driver of the observed transitions. Such an interpretation faces several theoretical challenges, and thus an alternative accretion-driven scenario cannot be excluded. The recent events observed in this quasar highlight the importance of spectroscopic monitoring of large active galactic nucleus samples on weeks-to-months timescales, which the SDSS-V is designed to achieve.Comment: Published in ApJ

Chondrocyte Deformations as a Function of Tibiofemoral Joint Loading Predicted by a Generalized High-Throughput Pipeline of Multi-Scale Simulations

Cells of the musculoskeletal system are known to respond to mechanical loading and chondrocytes within the cartilage are not an exception. However, understanding how joint level loads relate to cell level deformations, e.g. in the cartilage, is not a straightforward task. In this study, a multi-scale analysis pipeline was implemented to post-process the results of a macro-scale finite element (FE) tibiofemoral joint model to provide joint mechanics based displacement boundary conditions to micro-scale cellular FE models of the cartilage, for the purpose of characterizing chondrocyte deformations in relation to tibiofemoral joint loading. It was possible to identify the load distribution within the knee among its tissue structures and ultimately within the cartilage among its extracellular matrix, pericellular environment and resident chondrocytes. Various cellular deformation metrics (aspect ratio change, volumetric strain, cellular effective strain and maximum shear strain) were calculated. To illustrate further utility of this multi-scale modeling pipeline, two micro-scale cartilage constructs were considered: an idealized single cell at the centroid of a 100×100×100 μm block commonly used in past research studies, and an anatomically based (11 cell model of the same volume) representation of the middle zone of tibiofemoral cartilage. In both cases, chondrocytes experienced amplified deformations compared to those at the macro-scale, predicted by simulating one body weight compressive loading on the tibiofemoral joint. In the 11 cell case, all cells experienced less deformation than the single cell case, and also exhibited a larger variance in deformation compared to other cells residing in the same block. The coupling method proved to be highly scalable due to micro-scale model independence that allowed for exploitation of distributed memory computing architecture. The method’s generalized nature also allows for substitution of any macro-scale and/or micro-scale model providing application for other multi-scale continuum mechanics problems