Structures and Reactivity Patterns of Group 9 Metallocorroles

Group 9 metallocorroles 1-M(PPh_3) and 1-M(py)_2 [M = Co(III), Rh(III), Ir(III); 1 denotes the trianion of 5,10,15-tris-pentafluorophenylcorrole] have been fully characterized by structural, spectroscopic, and electrochemical methods. Crystal structure analyses reveal that average metal−N(pyrrole) bond lengths of the bis-pyridine metal(III) complexes increase from Co (1.886 Å) to Rh (1.957 Å)/Ir (1.963 Å); and the average metal−N(pyridine) bond lengths also increase from Co (1.995 Å) to Rh (2.065 Å)/Ir (2.059 Å). Ligand affinities for 1-M(PPh_3) axial coordination sites increase dramatically in the order 1-Co(PPh_3) < 1-Rh(PPh_3) < 1-Ir(PPh_3). There is a surprising invariance in the M(+/0) reduction potentials within the five- and six-coordinate corrole series, and even between them; the average M(+/0) potential of 1-M(PPh_3) is 0.78 V vs Ag/AgCl in CH_2Cl_2 solution, whereas that of 1-M(py)_2 is 0.70 V under the same conditions. Electronic structures of one-electron-oxidized 1-M(py)_2 complexes have been assigned by analysis of electron paramagnetic resonance spectroscopic measurements: oxidation is corrole-centered for 1-Co(py)_2 (g = 2.008) and 1-Rh(py)_2 (g = 2.003), and metal-centered for 1-Ir(tma)_2 (g_(zz) = 2.489, g_(yy) = 2.010, g_(xx) = 1.884, g_(av) = 2.128) and 1-Ir(py)_2 (g_(zz) = 2.401, g_(yy) = 2.000, g_(xx) = 1.937, g_(av) = 2.113)

Highly efficient 5\u27 capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at, and upstream of, the transcription start site and, in yeast and human cells, by intracellular NAD+ and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial transcriptional outputs, sensing NAD+ and NADH levels and adjusting transcriptional outputs accordingly. © 2018, Bird et al

Near Infrared Investigation of Polypropylene-Clay Nanocomposites for Further Quality Control Purposes-Opportunities and Limitations

YesPolymer nanocomposites are usually characterized using various methods, such as small angle X-ray diffraction (XRD) or transmission electron microscopy, to gain insights into the morphology of the material. The disadvantages of these common characterization methods are that they are expensive and time consuming in terms of sample preparation and testing. In this work, near infrared spectroscopy (NIR) spectroscopy is used to characterize nanocomposites produced using a unique twin-screw mini-mixer, which is able to replicate, at ~25 g scale, the same mixing quality as in larger scale twin screw extruders. We correlated the results of X-ray diffraction, transmission electron microscopy, G′ and G″ from rotational rheology, Young’s modulus, and tensile strength with those of NIR spectroscopy. Our work has demonstrated that NIR-technology is suitable for quantitative characterization of such properties. Furthermore, the results are very promising regarding the fact that the NIR probe can be installed in a nanocomposite-processing twin screw extruder to measure inline and in real time, and could be used to help optimize the compounding process for increased quality, consistency, and enhanced product propertie

Free-standing graphene films embedded in epoxy resin with enhanced thermal properties

The poor thermal conductivity of polymer composites has long been a deterrent to their increased use in high-end aerospace or defence applications. This study describes a new approach for the incorporation of graphene in an epoxy resin, through the addition of graphene as free-standing film in the polymeric matrix. The electrical and thermal conductivity of composites embedding two different free-standing graphene films was compared to composites with embedded carbon nanotube buckypapers (CNT-BP). Considerably higher thermal conductivity values than those achieved with conventional dispersing methods of graphene or CNTs in epoxy resins were obtained. The characterisation was complemented with a study of the structure at the microscale by cross-sectional scanning electron microscopy (SEM) images and a thermogravimetric analysis (TGA). The films are preconditioned in order to incorporate them into the composites, and the complete manufacturing process proposed allows the production and processing of these materials in large batches. The high thermal conductivity obtained for the composites opens the way for their use in demanding thermal management applications, such as electronic enclosures or platforms facing critical temperature loads.European Defence Agency tender No 17.ESI.OP.066. Study on the Impact of Graphene on Defence Application

Intersectional identities and dilemmas in interactions with health care professionals: An interpretative phenomenological analysis of British gay Muslim men

Individual interviews were conducted with six self-identified Muslim gay men living in London focusing on their experience of health service use. Transcripts were analysed using Interpretative Phenomenological Analysis. Analysis identified two major themes: namely, the close(d) community and self-management with health care professionals, detailing participants’ concerns regarding the risks of disclosing sexuality; and the authentic identity: “you’re either a Muslim or you’re gay, you can’t be both”, which delineated notions of incommensurate identity. Analysis highlights the need for health practitioners to have insight into the complexity of intersectional identities, identity disclosure dynamics, and the negative = consequences of assumptions made, be these heteronormative or faith-related

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health

Cutaneous Squamous Cell Carcinoma, an Immunohistological Analysis

Background: To detect the presence of keratin in apparently non-keratinizing squamous cell carcinomas by immunoperoxidase staining. This is important because keratinizing tumours are less radiosensitive and non-keratinizing are more radio responsive. Methods: This prospective study was conducted at King Edward Medical College and Post Graduate Medical Institute, Lahore over six months, A total of 45 patients suffering from squamous cell carcinomas of skin were included in the study.Both H and E and immunoperoxidase stainings were performed. Positive and negative controls were set up. The results of both types of staining were compared for each case. Results: Four groups were identified. Nineteen cases showed obvious keratinization on both H and E and immunoperoxidase staining.Eight cases had doubtful keratinization on H and E but showed more obvious keratinization on immunoperoxidase staining. Seven cases were non-keratinizing on H and E staining but revealed keratin on immunoperoxidase analysis.Eleven cases were non-keratinizing on H and E as well as on immunoperoxidase analysis. Conclusion: Immunohistological technique can help us in revising and modifying our H and E impression of a squamous cell carcinoma. It can help us in better diagnosis of squamous cell cancers on basis of keratinizatio

Time Control or Size Control? Reducing Complexity and Improving Accuracy of Genetic Programming Models

Complexity of evolving models in genetic programming (GP) can impact both the quality of the models and the evolutionary search. While previous studies have proposed several notions of GP model complexity, the size of a GP model is by far the most researched measure of model complexity. However, previous studies have also shown that controlling the size does not automatically improve the accuracy of GP models, especially the accuracy on out of sample (test) data. Furthermore, size does not represent the functional composition of a model, which is often related to its accuracy on test data. In this study, we explore the {\em evaluation time} of GP models as a measure of their complexity; we define the evaluation time as the time taken to evaluate a model over some data. We demonstrate that the evaluation time reflects both a model’s size and its composition; also, we show how to measure the evaluation time reliably. To validate our proposal, we leverage four well-known methods to size-control but to control evaluation times instead of the tree sizes; we thus compare size-control with time-control. The results show that time-control with a nuanced notion of complexity produces more accurate models on 17 out of 20 problem scenarios. Even when the models have slightly greater times and sizes, time-control counterbalances via superior accuracy on both training and test data. The paper also argues that time-control can differentiate functional complexity even better in an identically-sized population. To facilitate this, the paper proposes Fixed Length Initialisation (FLI) that creates an identically-sized but functionally-diverse population. The results show that while FLI particularly suits time-control, it also generally improves the performance of size-control. Overall, the paper poses evaluation-time as a viable alternative to tree sizes to measure complexity in GP