Progress in the photodynamic therapy (PDT) of cancer should benefit from a rationale to predict the most efficient of a series of photosensitizers that strongly absorb light in the phototherapeutic window (650-800 nm) and efficiently generate reactive oxygen species (ROS = singlet oxygen and oxygen-centered radicals). We show that the ratios between the triplet photosensitizer-O2 interaction rate constant (kD) and the photosensitizer decomposition rate constant (kd), kD/kd, determine the relative photodynamic activities of photosensitizers against various cancer cells. The same efficacy trend is observed in vivo with DBA/2 mice bearing S91 melanoma tumors. The PDT efficacy intimately depends on the dynamics of photosensitizer-oxygen interactions: charge transfer to molecular oxygen with generation of both singlet oxygen and superoxide ion (high kD) must be tempered by photostability (low kd). These properties depend on the oxidation potential of the photosensitizer and are suitably combined in a new fluorinated sulfonamide bacteriochlorin, motivated by the rationale.

3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a widely abused, psychoactive recreational drug. There is growing evidence that the MDMA neurotoxic profile may be highly dependent on both its hepatic metabolism and body temperature. Metabolism of MDMA involves N-demethylation to 3,4-methylenedioxyamphetamine (MDA), which is also a drug of abuse. MDMA and MDA are O-demethylenated to N-methyl-␣-methyldopamine (N-Me-␣-MeDA) and ␣-methyldopamine (␣-MeDA), respectively, both of which are catechols that can undergo oxidation to the corresponding ortho-quinones. In the presence of glutathione (GSH), ortho-quinones may be conjugated with GSH to form glutathionyl adducts. In this study, we evaluated the neurotoxicity of MDMA and three of its metabolites obtained by synthesis, N-Me-␣-MeDA, ␣-MeDA, and 5-(GSH)-␣-MeDA [5-(glutathion-S-yl)-␣-methyldopamine] in rat cortical neuronal serum-free cultures under normal (36.5°C) and hyperthermic (40°C) conditions. Cell viability was assessed, and the mechanism of cell death was also evaluated. Our study shows that these metabolites are more neurotoxic [5-(GSH)-␣-MeDA being the most toxic] than the parent compound MDMA. The neurotoxicity of MDMA metabolites was partially prevented by the antioxidants N-acetylcystein and also, in a minor extent, by ␣-phenyl-N-tert-butyl nitrone. All the tested compounds induced apoptotic cell death in cortical neurons, and their neurotoxic effect was potentiated under hyperthermic conditions. These data suggest that MDMA metabolites, especially under hyperthermic conditions, contribute to MDMA-induced neurotoxicity.

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A key challenge in project management is to understand to which extent the dynamic interactions between the different project people-through formal and informal networks of collaboration that temporarily emerge across a project´s lifecycle-throughout all the phases of a project lifecycle, influence a project's outcome. This challenge has been a growing concern to organizations that deliver projects, due their huge impact in economic, environmental, and social sustainability. In this work, a heuristic two-part model, supported with three scientific fields-project management, risk management, and social network analysis-is proposed, to uncover and measure the extent to which the dynamic interactions of project people-as they work through networks of collaboration-across all the phases of a project lifecycle, influence a project's outcome, by first identifying critical success factors regarding five general project collaboration types ((1) communication and insight, (2) internal and cross collaboration, (3) know-how and power sharing, (4) clustering, and (5) teamwork efficiency) by analyzing delivered projects, and second, using those identified critical success factors to provide guidance in upcoming projects regarding the five project collaboration types.Sustainability 2020, 12, 1503 2 of 32 competency and training are important factors, it is almost always the network factor that is the big key predictor of high performance in organizations and are usually characterized by having broader and diverse problem-solving networks fueled with positive energy [20]. But a broader network does not necessarily mean larger in size. Furthermore, some authors argue that when it comes to effective networks of collaboration, bigger does not always means better, but rather, superior quality means better [7,8]. However, creating a broad and diverse problem-solving network usually requires an extra mile from the employees of an organization, essentially because they need to be more flexible, accountable, and empowered, and proactively search and maintain such networks. This also means that more work will be done through informal networks of relationships, removing to a certain extent, the role of the formal organizational structure in several ways [8,21]. In fact, building a broader and more diverse problem-solving network requires a proper organizational structure that enables people to strategically create the necessary connections in an energized way. Usually, due its rigid nature, a formal organizational structure [6] is not able to provide for the needs of building such problem-solving networks [8,22]. However, either under the pressure or when highly motivated to get the work done, employees of an organization naturally engage in informal networks of collaboration, in order to overcome the natural constraints of the formal organizational structure to get the work done [8,22,23]. Very often these emerging informal networks are not ruled by the rational-legal authority system that the formal organizational structure provides ba...

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The development of large scale synthesis of enantiopure and thermally stable (R)- and (S)-BINOL molecules constitutes a key milestone in the field of asymmetric catalysis. Particularly, a great variety of chiral binaphthyl-based phosphorus compounds, herein represented by phosphite and phosphine classes, have earned considerable relevance due to their versatility as ligands in enantioselective metal-catalysed reactions, allowing the preparation of optically active products with the desired enantiopurity. This review highlights the most relevant concepts and accounts regarding general synthetic procedures for binaphthyl-based mono- and bidentate phosphites and phosphines. Furthermore, the search for environmentally benign chemical catalytic processes compelled us to also give special attention to the functionalisation of binaphthyl-based phosphorus ligands for use in alternative reaction media. When available, a critical selection of their applications in catalysis is briefly assessed.

The in vitro phototoxicity of a photostable, synthetic, water-soluble, halogenated bacteriochlorin, 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl)bacteriochlorin (TCPBSO3H), toward mouse melanoma (S91) cells is ∼60-fold higher than that of the analogous porphyrin, and is associated with very weak toxicity in the dark; 90% of S91 cells were killed in response to a light dose of 0.26 J cm(-2) in the presence of [TCPBSO3H]=5 μM. In vivo toxicity toward DBA mice is very low, even at doses of 20 mg kg(-1). In vivo pharmacokinetics and biodistribution of TCPBSO3H were studied in DBA mice with S91 tumors; 24 h after intraperitoneal injection of 10 mg kg(-1), TCPBSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue ratios of 3 and 5 for muscle and skin, respectively. Photodynamic therapy (PDT) performed under these conditions, with 90 mW cm(-2) diode laser irradiation at λ 750 nm for 20 min (total light dose of 108 J cm(-2)), resulted in tumor regression. Tumor recurrence was observed only approximately two months after treatment, confirming the efficacy of this PDT against melanoma.

360°video is attracting an increasing amount of attention in the context of Virtual Reality (VR). Owing to its very high-resolution requirements, existing professional streaming services for 360°video suffer from severe drawbacks. This paper introduces a novel end-to-end streaming system from encoding to displaying, to transmit 8K resolution 360°v ideo and to provide an enhanced VR experience using Head Mounted Displays (HMDs). The main contributions of the proposed system are about tiling, integration of the MPEG-Dynamic Adaptive Streaming over HTTP (DASH) standard, and viewport-aware bitrate level selection. Tiling and adaptive streaming enable the proposed system to deliver very high-resolution 360°video at good visual quality. Further, the proposed viewport-aware bitrate assignment selects an optimum DASH representation for each tile in a viewportaware manner. The quality performance of the proposed system is verified in simulations with varying network bandwidth using realistic view trajectories recorded from user experiments. Our results show that the proposed streaming system compares favorably compared to existing methods in terms of PSNR and SSIM inside the viewport.