Structural and catalytic studies on novel copper complexes

Transition metal complexes and their chemistry are providing synthetic chemists and the chemical industry with simpler and less tedious synthetic procedures but also opened endless doors to new synthetic transformations that had been thought impossible. The main advantage of transition metal chemistry is that these complexes are often used in substoichiometric amounts to perform the desired reaction. Other benefits such as high atom efficiency or fewer amount of by-products are often observed as well. Despite all these advantages, the commonly utilised transition metals are either expensive, toxic, and/or prospected from politically unstable regions. Copper, a less toxic and economical transition metal, circumvents these downsides. The first Chapter outlines a brief overview of Schiff bases and their utilisation in transition metal chemistry including a discussion on diazabutadiene (DAB) and iminopyridine (ImPy) ligands, their complexes, and their reported applications. Furthermore, it includes the accounts for the preparation of DAB and ImPy ligands and their novel copper(I) complexes. The characterisation and X-ray structures of these complexes and in depth studies into the solution behaviour of [Cu(DAB)] complexes are discussed as well. The second Chapter outlines an introduction to the chemistry of amines. It gives a brief overview over their importance in chemistry and their preparation, and a focus on the synthesis of primary amines from azide precursors. Furthermore, the utilisation of amines in the hydroamination reaction is reviewed and the application of copper(I) complexes in the literature is examined. In Chapter 3, results of our successful attempts to exploit [Cu(DAB)] in the reduction of aryl azides are presented. In addition, computational studies are included to introduce the proposed reaction mechanism. The fourth Chapter includes our efforts to apply the prepared copper(I) complexes in the intra- and intermolecular hydroamination reaction of primary and secondary amines to a variety of carbon–carbon unsaturated bonds. The preparation for the various starting materials and the isolation of their corresponding products is discussed. The fifth Chapter provides a summary and the general conclusions of our studies and the final Chapter contains all experimental procedures and characterisation data for all compounds synthesised during this project.Open Acces

Reducing prostaglandin E2 production to raise cancer immunogenicity

Cyclooxygenases (COX), commonly upregulated in numerous cancers, generate prostaglandin E2 (PGE2), which has been implicated in key aspects of malignant growth including proliferation, invasion and angiogenesis. Recently, we showed that production of PGE2 by cancer cells dominantly enables progressive tumor growth via immune escape and that cyclooxygenase inhibitors synergize with immunotherapy to enhance tumor eradication

Homo- and Heteroleptic Copper(I) Complexes with Diazabutadiene Ligands: Synthesis, Solution- and Solid-State Structural Studies

The preparation of novel copper(I) complexes of diazabutadiene (DAB) ligands with aliphatic backbones is reported. [Cu(DABR)2](BF4), [Cu(DABR)(NCMe)2](BF4) and [CuCl(DABR)] are easily synthesised and air-stable. These complexes, which remain scarce in the literature, have been fully characterised, and their behaviour both in the solid state as well as in solution has been studied by means of X-ray crystallography, NMR and UV/Vis spectroscopy

Prostaglandin E₂ impacts multiple stages of the natural killer cell antitumor immune response

Tumor immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumors can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on Natural killer (NK) cells to inhibit antitumor immunity. However, precisely how PGE2 influences NK cell tumor-restraining functions remains unclear. Here, we report that following PGE₂ treatment, human NK cells exhibited altered expression of specific activating receptors and a reduced ability to degranulate and kill cancer targets. Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Using live cell imaging, we showed that in the presence of PGE2, NK cells were slower and less likely to kill cancer target cells following conjugation. Imaging the sequential stages of NK cell killing revealed that PGE₂ impaired NK cell polarization, but not the re-organization of synaptic actin or the release of perforin itself. Together, these findings demonstrate that PGE₂ affects multiple but select NK cell functions. Understanding how cancer cells subvert NK cells is necessary to more effectively harness the cancer-inhibitory function of NK cells in treatments

Measurement of influence of network impairments on VoIP call quality

Práca skúma, analyzuje a vyhodnocuje vplyv nežiaducich faktorov v IP sieťach na prenos hlasu VoIP. Rozoberá problematiku prenosu hlasu cez paketové siete v rámci noriem a zaužívaných pravidiel. V teoretickej časti sú vysvetlené pojmy a problematika VoIP sietí, so zameraním sa na fakty, potrebné k plnému pochopeniu skúmaných dejov a meraní. V praktickej časti je zhrnutá realizácia konkrétnych testov, podľa zadania práce s orientáciou na prvotné overenie si zariadení i hodnotiacich modelov a následné meranie vplyvu javov na kvalitu hovorov, s použitím týchto zariadení a ústredne Asterisk.This work explores, analyzes and rates influence of network impairments on VoIP traffic. It describes how voice over IP is carried according to standards. There are described concepts and basics of VoIP networks with orientation on facts necessary to understand analyzed actions and measurements in theoretical part. In practical part, there is described realization of tests according to instructions with orientation on initial checking of devices and rating models and then measurement of influence of network impairments on quality of calls with use of these devices and Opensource PBX Asterisk.

Elucidation of role of graphene in catalytic designs for electroreduction of oxygen

Graphene is, in principle, a promising material for consideration as component (support, active site) of electrocatalytic materials, particularly with respect to reduction of oxygen, an electrode reaction of importance to low-temperature fuel cell technology. Different concepts of utilization, including nanostructuring, doping, admixing, preconditioning, modification or functionalization of various graphene-based systems for catalytic electroreduction of oxygen are elucidated, as well as important strategies to enhance the systems' overall activity and stability are discussed

Chapter Operationalizing Heterogeneous Data-Driven Process Models for Various Industrial Sectors through Microservice-Oriented Cloud-Based Architecture

Industrial performance optimization increasingly makes the use of various analytical data-driven models. In this context, modern machine learning capabilities to predict future production quality outcomes, model predictive control to better account for complex multivariable environments of process industry, Bayesian Networks enabling improved decision support systems for diagnostics and fault detection are some of the main examples to be named. The key challenge is to integrate these highly heterogeneous models in a holistic system, which would also be suitable for applications from the most different industries. Core elements of the underlying solution architecture constitute highly decoupled model microservices, ensuring the creation of largely customizable model runtime environments. Deployment of isolated user-space instances, called containers, further extends the overall possibilities to integrate heterogeneous models. Strong requirements on high availability, scalability, and security are satisfied through the application of cloud-based services. Tieto successfully applied the outlined approach during the participation in FUture DIrections for Process industry Optimization (FUDIPO), a project funded by the European Commission under the H2020 program, SPIRE-02-2016

Evaluation of Reduced-Graphene-Oxide Aligned with WO3-Nanorods as Support for Pt Nanoparticles during Oxygen Electroreduction in Acid Medium

Hybrid supports composed of chemically-reduced graphene-oxide-aligned with tungsten oxide nanowires are considered here as active carriers for dispersed platinum with an ultimate goal of producing improved catalysts for electroreduction of oxygen in acid medium. Here WO3 nanostructures are expected to be attached mainly to the edges of graphene thus making the hybrid structure not only highly porous but also capable of preventing graphene stacking and creating numerous sites for the deposition of Pt nanoparticles. Comparison has been made to the analogous systems utilizing neither reduced graphene oxide nor tungsten oxide component. By over-coating the reduced-graphene-oxide support with WO3 nanorods, the electrocatalytic activity of the system toward the reduction of oxygen in acid medium has been enhanced even at the low Pt loading of 30 microg cm-2. The RRDE data are consistent with decreased formation of hydrogen peroxide in the presence of WO3. Among important issues are such features of the oxide as porosity, large population of hydroxyl groups, high Broensted acidity, as well as fast electron transfers coupled to unimpeded proton displacements. The conclusions are supported with mechanistic and kinetic studies involving double-potential-step chronocoulometry as an alternative diagnostic tool to rotating ring-disk voltammetry.Comment: arXiv admin note: text overlap with arXiv:1805.0315

Regulatory T Cells Selectively Express Toll-like Receptors and Are Activated by Lipopolysaccharide

Regulatory CD4 T cells (Treg) control inflammatory reactions to commensal bacteria and opportunist pathogens. Activation of Treg functions during these processes might be mediated by host-derived proinflammatory molecules or directly by bacterial products. We tested the hypothesis that engagement of germline-encoded receptors expressed by Treg participate in the triggering of their function. We report that the subset of CD4 cells known to exert regulatory functions in vivo (CD45RBlow CD25+) selectively express Toll-like receptors (TLR)-4, -5, -7, and -8. Exposure of CD4+ CD25+ cells to the TLR-4 ligand lipopolysaccharide (LPS) induces up-regulation of several activation markers and enhances their survival/proliferation. This proliferative response does not require antigen-presenting cells and is augmented by T cell receptor triggering and interleukin 2 stimulation. Most importantly, LPS treatment increases CD4+ CD25+ cell suppressor efficiency by 10-fold and reveals suppressive activity in the CD4+ CD45RBlow CD25− subset that when tested ex-vivo, scores negative. Moreover, LPS-activated Treg efficiently control naive CD4 T cell–dependent wasting disease. These findings provide the first evidence that Treg respond directly to proinflammatory bacterial products, a mechanism that likely contributes to the control of inflammatory responses

Efficient and versatile manipulation of the peripheral CD4+ T-cell compartment by antigen targeting to DNGR-1/CLEC9A

DC NK lectin group receptor-1 (DNGR-1, also known as CLEC9A) is a C-type lectin receptor expressed by mouse CD8α+ DC and by their putative equivalents in human. DNGR-1 senses necrosis and regulates CD8+ T-cell cross-priming to dead-cell-associated antigens. In addition, DNGR-1 is a target for selective in vivo delivery of antigens to DC and the induction of CD8+ T-cell and Ab responses. In this study, we evaluated whether DNGR-1 targeting can be additionally used to manipulate antigen-specific CD4+ T lymphocytes. Injection of small amounts of antigen-coupled anti-DNGR-1 mAb into mice promoted MHC class II antigen presentation selectively by CD8α+ DC. In the steady state, this was sufficient to induce proliferation of antigen-specific naïve CD4+ T cells and to drive their differentiation into Foxp3+ regulatory lymphocytes. Co-administration of adjuvants prevented this induction of tolerance and promoted immunity. Notably, distinct adjuvants allowed qualitative modulation of CD4+ T-cell behavior: poly I:C induced a strong IL-12-independent Th1 response, whereas curdlan led to the priming of Th17 cells. Thus, antigen targeting to DNGR-1 is a versatile approach for inducing functionally distinct CD4+ T-cell responses. Given the restricted pattern of expression of DNGR-1 across species, this strategy could prove useful for developing immunotherapy protocols in humans