The AzTEC mm-Wavelength Camera

AzTEC is a mm-wavelength bolometric camera utilizing 144 silicon nitride micromesh detectors. Herein we describe the AzTEC instrument architecture and its use as an astronomical instrument. We report on several performance metrics measured during a three month observing campaign at the James Clerk Maxwell Telescope, and conclude with our plans for AzTEC as a facility instrument on the Large Millimeter Telescope.Comment: 13 pages, 15 figures, accepted for publication in Monthly Notice

YREC: The Yale Rotating Stellar Evolution Code

The stellar evolution code YREC is outlined with emphasis on its applications to helio- and asteroseismology. The procedure for calculating calibrated solar and stellar models is described. Other features of the code such as a non-local treatment of convective core overshoot, and the implementation of a parametrized description of turbulence in stellar models, are considered in some detail. The code has been extensively used for other astrophysical applications, some of which are briefly mentioned at the end of the paper.Comment: 10 pages, 2 figures, ApSS accepte

Real world, multicentre patterns of treatment and survival in metastatic renal cell carcinoma with the UK Renal Oncology Collaborative (UK ROC): Is it time to look favourably on first-line immunotherapy containing combinations in all IMDC groups?

\ua9 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.Introduction: Clinical trials show improved progression-free survival (PFS) and overall survival (OS) in first-line metastatic renal cell carcinoma (mRCC) patients with immunotherapy containing systemic anti-cancer therapies (SACT). However, in the favourable international metastatic renal cell cancer database consortium (IMDC) group there is no trial evidence for OS benefit despite clear PFS improvement when comparing anti-VEGF tyrosine kinase inhibitor (TKI) monotherapy and (immunotherapy and TKI) IO/TKI combinations. Objective: To assess the impact of first-line SACT choice on the clinical outcomes of PFS and OS in mRCC. To evaluate this impact of initial SACT for allcomers and the favourable IMDC group. Methods: A multicentre retrospective review of patients who started SACT for mRCC (01/01/2018–30/06/2021) at 17 UK NHS trusts. Patient demographics and IMDC group were analysed. Survival data were compared using Kaplan–Meier curves, and the statistical significance of differences in outcome between the groups was assessed with the log-rank test. Univariable and multivariable Cox proportional hazard modelling estimate the hazard ratios (HRs) for survival outcomes associated with IMDC and treatment subtype. Results: One thousand three hundred and nineteen patients were identified with a median age of 64. 294 (22.3%), 695 (52.7%) and 321 (24.3%) were IMDC group favourable, intermediate and poor, respectively. 311 (23.6%), 197 (14.9%) and 778 (59%) patients received checkpoint inhibitor and anti-CTLA4 monoclonal antibody (IO/IO), IO/TKI and TKI first-line SACT across all IMDC groups. Significant PFS improvement favouring IO/TKI versus TKI was demonstrated in allcomers HR = 0.61. In the favourable risk group, Log rank testing demonstrated a significant benefit for IO/TKI over TKI for PFS (HR = 0.60, 95% CI [0.39, 0.91]) and OS (HR = 0.42, 95% CI [0.18, 0.99]). Conclusion: In this real-world evidence cohort, we have shown OS and PFS benefit with IO/TKI versus TKI in the favourable IMDC risk group. This has not been previously reported from trial outcomes and would support use of front-line IO/TKI in mRCC favourable risk patients

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Influence of structural isomerism and fluorine atom substitution on the self-association of naphthoic acid

The self-association of small aromatic systems driven by π-π stacking and hydrophobic interactions is well known. Understanding the nature of these interactions is important if they are to be used to control association. Here, we present results of an NMR study into the self-association of two isomers of naphthoic acid along with an investigation into the role of a fluorine substituent on that self- association. We interpret the results in terms of a simple isodesmic model of self- association and show that the addition of the fluorine atom appears to increase the stability of the aggregates by an order of magnitude (e.g. 1-naphothic acid vs 4- fluoro-1-naphthoic acid Keq = 0.05 increases to 0.35 M-1), a result which is supported by computational studies in the literature on the role of substituent effects on interaction energy. The use of fluorinated isomers to probe the assembly is also presented, with differing trends in fluorine-19 chemical shifts observed depending on the isomer substitution pattern

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer : long-term survival results from the STAMPEDE trial

Background STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. Methods We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. Results Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P  0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). Conclusions The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden

Artemisinin Inhibits Chloroplast Electron Transport Activity: Mode of Action

Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo), behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the QB; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth

Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits

Purpose: Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model. Methods: A full-depth chondral defect along with subchondral bone injury were originated in the knee joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation. Results: Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface. Conclusions: Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.This study was supported by the Spanish Ministry of Science and Innovation through MAT2010-21611-C03-00 project (including the FEDER financial support), by Conselleria de Educacion (Generalitat Valenciana, Spain) PROMETEO/2011/084 grant, and by CIBER-BBN en Bioingenieria, Biomateriales y Nanomedicina. The work of JLGR was partially supported by funds from the Generalitat Valenciana, ACOMP/2012/075 project. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the - Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Sancho-Tello Valls, M.; Forriol, F.; Gastaldi, P.; Ruiz Sauri, A.; Martín De Llano, JJ.; Novella-Maestre, E.; Antolinos Turpín, CM.... (2015). 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