P 419 Comparison of tight junctions permeability and modulation in iris pigment epithelium and retinal pigment epithelium in vitro

Amb una superfície: 0,61 ha, de basalt i aigua nebulitzada.Barragán, Pedro (dissenyador)Gran pla general de El Volcà,conegut com la Carbonera. El carbó calent era mullat per aigua subterrània i desprenia vapor. Actualment està inactiu. Destaquen el pg. Josep Carner amb el monument a Colom i els edificis de Capitania i Duana

On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds.

Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective, on-resin N-methylation of cyclic peptides to generate compounds with drug-like membrane permeability and oral bioavailability. The selectivity and degree of N-methylation of the cyclic peptide was dependent on backbone stereochemistry, suggesting that conformation dictates the regiochemistry of the N-methylation reaction. The permeabilities of the N-methyl variants were corroborated by computational studies on a 1,024-member virtual library of N-methyl cyclic peptides. One of the most permeable compounds, a cyclic hexapeptide (molecular mass = 755 Da) with three N-methyl groups, showed an oral bioavailability of 28% in rat

Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44)†

Background We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). Patients and methods Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m2; q3w) followed by four cycles docetaxel (100 mg/m2; q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. Results TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. Conclusions The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rate

Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD?

Item does not contain fulltextThis study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).17 p

Identification of Vanadium on Iron Ore Sample from a Depo-sit in Choghart Area, Iran from Beneficiation Point of View

Large deposits of titanoferous vanadium bearing magnet-ites have been reported from different parts of Iran including those of Choghart area which are rich in vanad-ium. These deposits cannot be directly used for the prod-uction of vanadium because of the unknown feature and characteristics of vanadium in the deposits. To know the mineralogical composition, shape of the particles, chemi-cal character and mesh of grind which play vial role in flowsheet design, samples from Choghart have been subjec-ted to detailed mineralogical and microscopic studies especially SEM, sieve analysis, liberation studies using Davis tube, sink and float tests and particle counting methods and chemical analysis. The results show that most of vanadium is present in magnetite minerals analysing V205 0.45%.Magnetite, hematite, talc (as major minerals) and apatite, calcite, goethite, feldspars, amphibole and pyroxene (as minor minerals) are present in the order of abundance and liberation studies have shown that most of the magnetite particles are free at below 150 microns in which, vanadium element replaced iron, in magnetite structure. This and evenly distribution of vanadium in magnetite sample were further confirmed by SEM technique. Based on the characterization studies carried out it can be predicted, that the combination of low intensity magnetic separation, roasting and leaching would the possible techniques to recover vanadium without ineffective destruction of magnetite structure

Characterization and Lytic Activity of Isolated Escherichia coli Bacteriophages against Escherichia coli in vitro.

Escherichia coli (E. coli) is the most common cause of urinary tract infection (UTI) and typically treated with antibiotics. Unrestricted use of antibiotics may lead to the emergence of antibiotic-resistant bacteria. The present study aimed to isolate and characterize phages against E. coli from infected urine samples and to determine the lytic activity of phages against E. coliin vitro. The present experimental study was conducted in the Laboratory of Bouali Sina Hospital (Sari, Iran) in May 2018. E. coli was identified from nine urine samples of patients with UTI using conventional microbiological methods. Bacteriophages were isolated from the infected urine specimens, and their lytic activity was determined using the spot test. The titer of the bacteriophages was measured using the double-layer agar technique. The morphology of the bacteriophages was revealed using transmission electron microscopy, and the latent time period and burst size were determined. Data were analyzed using the SPSS software package. E. coli was isolated from nine infected urine samples. The lytic activity of bacteriophages against E. coli was determined using the spot test by observing the formation of inhibition zones. Transmission electron microscopy showed E. coli phages belonging to the Myoviridae family. The latent time period was 20 minutes with a burst size of 1,200 plaque-forming unit (PFU) per infected cell. The results of the double-layer agar assay showed that the titer of bacteriophages was 20×10 <sup>8</sup> PFU/mL. The E. coli bacteriophage was isolated from infected urine samples and characterized, and their lytic activity against E. coli was determined in vitro

OTX015 (MK-8628), a novel BET inhibitor, exhibits antitumor activity in non-small cell and small cell lung cancer models harboring different oncogenic mutations.

Inhibitors targeting epigenetic control points of oncogenes offer a potential mean of blocking tumor progression in small cell and non-small cell lung carcinomas (SCLC, NSCLC). OTX015 (MK-8628) is a BET inhibitor selectively blocking BRD2/3/4. OTX015 was evaluated in a panel of NSCLC or SCLC models harboring different oncogenic mutations. Cell proliferation inhibition and cell cycle arrest were seen in sensitive NSCLC cells. MYC and MYCN were downregulated at both the mRNA and protein levels. In addition, OTX015-treatment significantly downregulated various stemness cell markers, including NANOG, Musashi-1, CD113 and EpCAM in H3122-tumors in vivo. Conversely, in SCLC models, weak antitumor activity was observed with OTX015, both in vitro and in vivo. No predictive biomarkers of OTX015 activity were identified in a large panel of candidate genes known to be affected by BET inhibition. In NSCLC models, OTX015 was equally active in both EML4-ALK positive and negative cell lines, whereas in SCLC models the presence of functional RB1 protein, which controls cell progression at G1, may be related to the final biological outcome of OTX015. Gene expression profiling in NSCLC and SCLC cell lines showed that OTX015 affects important genes and pathways with a very high overlapping between both sensitive and resistant cell lines. These data support the rationale for the OTX015 Phase Ib (NCT02259114) in solid tumors, where NSCLC patients with rearranged ALK gene or KRAS-positive mutations are currently being treated

The Economics of 1.5°C Climate Change

The economic case for limiting warming to 1.5°C is unclear, due to manifold uncertainties. However, it cannot be ruled out that the 1.5°C target passes a cost-benefit test. Costs are almost certainly high: The median global carbon price in 1.5°C scenarios implemented by various energy models is more than US$100 per metric ton of CO2 in 2020, for example. Benefits estimates range from much lower than this to much higher. Some of these uncertainties may reduce in the future, raising the question of how to hedge in the near term. Maintaining an option on limiting warming to 1.5°C means targeting it now. Setting off with higher emissions will make 1.5°C unattainable quickly without recourse to expensive large-scale carbon dioxide removal (CDR), or solar radiation management (SRM), which can be cheap but poses ambiguous risks society seems unwilling to take. Carbon pricing could reduce mitigation costs substantially compared with ramping up the current patchwork of regulatory instruments. Nonetheless, a mix of policies is justified and technology-specific approaches may be required. It is particularly important to step up mitigation finance to developing countries, where emissions abatement is relatively cheap

Real or imagined women? Staff representations of international women postgraduate students

In Australia\u27s globalising universities many support staff and teaching staff now work with international women postgraduate students. But are they aware of the issues facing these women, and is their understanding of them adequate? Indeed, how do they represent them? In this paper we draw on a small-scale pilot study involving key university personnel. We argue that the ways in which such staff represent this group of students is problematic. Focusing primarily on academic issues and on the literature on learning styles, we analyse these staff members\u27 representations of international women postgraduate students from a postcolonial perspective. We explore the extent to which such representations, and the learning styles literature that reflects and informs them, are what Edward Said calls \u27Orientalist\u27. In so doing, we point to both the constitution of the international woman student as postcolonial female subject and show how this situates her in relation to the prevalent learning styles discourse. Further we argue that such representations of the students differ in crucial ways from the students\u27 self-representations, suggesting that in certain subtle ways such staff members are engaging with \u27imagined\u27 rather than \u27real\u27 women. <br /

Air and water pollution over time and industries with stochastic dominance

We employ a stochastic dominance (SD) approach to analyze the components that contribute to environmental degradation over time. The variables include countries\u2019 greenhouse gas (GHG) emissions and water pollution. Our approach is based on pair-wise SD tests. First, we study the dynamic progress of each separate variable over time, from 1990 to 2005, within 5-year horizons. Then, pair-wise SD tests are used to study the major industry contributors to the overall GHG emissions and water pollution at any given time, to uncover the industry which contributes the most to total emissions and water pollution. While CO2 emissions increased in the first order SD sense over 15 years, water pollution increased in a second-order SD sense. Electricity and heat production were the major contributors to the CO2 emissions, while the food industry gradually became the major water polluting industry over time. SD sense over 15 years, water pollution increased in a second-order SD sense. Electricity and heat production were the major contributors to the CO2 emissions, while the food industry gradually