Precious metal complexes of bis(pyridyl)allenes: synthesis and catalytic and medicinal applications

The incorporation of donor-type substituents on the allene core opens up the possibility of coordination complexes in which the metal is bonded to the donor groups, with or without interaction with the double bond system. Despite the challenges in the synthesis of such allene-containing metal complexes, their unique 3D environments and dual functionality (allene and metal) could facilitate catalysis and interaction with chemical and biological systems. Bis(pyridyl)allenes are presented here as robust ligands for novel Pd(II), Pt(IV) and Au(III) complexes. Their synthesis, characterisation and first application as catalysts of benchmark reactions for Pd, Pt and Au are presented with interesting reactivity and selectivities. The complexes have also been probed as antimicrobial and anticancer agents with promising activities, and the first studies on their unusual interaction with several DNA structures will open new avenues for research in the area of metallodrugs with new mechanisms of action

All-optical inverter based on polarization switching in long-wavelength VCSELs

All-optical processing of high-speed signals is expected to be a key technology in future photonic networks. VCSELs are very promising devices for these applications due to their inherent advantages. Nonlinear transfer functions can be obtained by using optical injection because it strongly affects the transverse mode and polarization characteristics of VCSELs [1]. Optical injection can be used to obtain polarization switching (PS) of single transverse mode VCSELs. When the polarization of an injected optical field is orthogonal to that of the solitary VCSEL (orthogonal optical injection), PS and bistability are observed [2]. PS by optical injection is expected to be fast and thus suitable for application in all-optical signal-processing systems. In this work we report, for the first time to our knowledge, all-optical inversion operation using PS in a 1550nm single-mode VCSEL induced by orthogonal optical injection. We demonstrate all-optical inversion for NRZ signals at a bit rate of 2.5 Gb/s. An all-fiber system has been developed in order to inject the light from a tunable laser into a commercial 1550nm-VCSEL (RayCan, Co.). The free-running VCSEL emits in the fundamental transverse mode with a linear polarization (parallel polarization) over the whole current range. The subsidiary orthogonal polarization is shifted 0.48 nm to the long wavelength side with respect to the dominant one. Pulsed optical injection was obtained by using a pulse pattern generator and a Mach-Zhender intensity modulator. © 2011 IEEE

Qualitative and quantitative characterization of a coal power plant waste by TG/DSC/MS, XRF and XRD

SO2 removal from coal-fired power plant flue gases can be done by dry, semi-dry or wet desulphurization processes, using limestone or lime-containing products as sorbents. In a Brazilian coal power plant, there is a dry desulphurization unit to capture SO2 with hydrated lime from the combustion gases. A part of the flying ashes produced is mixed with the bottom coal ashes and the spent sulphated product generated after SO2 capture. This residual solid blend is then buried in a non-productive area, from which coal was already extracted and is studied in this work. According to the authors’ experience in the development and characterization of adsorbents for low temperature dry desulphurization processes and in thermogravimetric analysis, this paper shows and discusses a method which was developed to characterize qualitatively and quantitatively the chemical and mineral composition of this waste by using thermogravimetry coupled with mass spectrometry, X-ray fluorescence and X-ray diffraction, to preview new potential industrial applications for this waste.We are thankful to the University of Cantabria for the financial support under the Project: 51.VP61.64005, to the Brazilian Research Council, under the project CNPq no. 407005/2013-7, and to the Brazilian Education Council CAPES

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Angiosarcoma of the nasal cavity: a case report

Angiosarcomas are malignant neoplasias of rapid growth that develop from endothelial cells. They represent 2% of all sarcomas and only 1–4% are located in the aerodigestive tract. Since 1977, only 16 cases have been reported

Inflammatory Adipokines, High Molecular Weight Adiponectin, and Insulin Resistance: A Population-Based Survey in Prepubertal Schoolchildren

BackgroundThe aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.MethodologyWe studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.Principal findingsLeptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (pConclusionsIn prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance

Proteomic approach used in the diagnosis of Riedel's thyroiditis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Riedel's thyroiditis, a rare thyroid disease, can be difficult to diagnose prior to surgical removal and can be confused with malignancy both clinically and cytologically.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old Caucasian woman who presented with a goiter, which showed a rapid increase in size at ultrasound check, suggesting malignancy. Because of inconclusive cytology, a total thyroidectomy was performed. Fine-needle aspiration of the removed thyroid was processed by two-dimensional electrophoresis, and the proteome was compared with both anaplastic cancer and control samples. Significant differentially expressed protein spots were identified by Western blot analysis by using specific antibodies.</p> <p>Conclusions</p> <p>The protein pattern of Riedel's fine-needle aspiration revealed a superimposition with that of the control samples. The comparison of the protein pattern of Riedel's thyroiditis fine-needle aspiration with that of anaplastic cancer showed evidence of a different expression of ferritin heavy chains, ferritin light chains, and haptoglobins, as previously reported in thyroid cancers. Therefore, we performed Western blot analysis of these proteins and validated that their expression levels were low or absent in Riedel's thyroiditis and control samples despite the high concentrations present in fine-needle aspiration anaplastic samples. The concurrent absent or low expression levels of haptoglobin, ferritin light chain, and ferritin heavy chain in Riedel's thyroiditis fine-needle aspiration samples strongly indicate the benign nature of the thyroid lesion. These results suggest the potential applicability of fine-needle aspiration proteome analysis for Riedel's thyroiditis diagnosis.</p

Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. FINDINGS: Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8-10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6-4·2] vs 1·4 months [1·4-1·6]; hazard ratio 0·37; 95% CI 0·25-0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. INTERPRETATION: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. FUNDING: Agios Pharmaceuticals