The String Landscape, the Swampland, and the Missing Corner

We give a brief overview of the string landscape and techniques used to construct string compactifications. We then explain how this motivates the notion of the swampland and review a number of conjectures that attempt to characterize theories in the swampland. We also compare holography in the context of superstrings with the similar, but much simpler case of topological string theory. For topological strings, there is a direct definition of topological gravity based on a sum over a "quantum gravitational foam." In this context, holography is the statement of an identification between a gravity and gauge theory, both of which are defined independently of one another. This points to a missing corner in string dualities which suggests the search for a direct definition of quantum theory of gravity rather than relying on its strongly coupled holographic dual as an adequate substitute (Based on TASI 2017 lectures given by C. Vafa)

The "Click-tail approach" for the design and synthesis of novel carbonic anhydrase inhibitors

The Carbonic Anhydrases (CAs) are a family of zinc enzymes deputed to the interconversion of carbonic dioxide to hydrogen carbonate. Herein, we report on a sustainable modular strategy, also called "clicktail approach", used to obtain two series of 4-(4-substituted-lH-l,2,3-triazol-lyl) benzenesulfonamides. Design and synthesis strategies, x-ray derived CA-ligand binding mode and enzyme-based inhibition results will be presented

Heat Transfer Analysis of Damaged Shrouded High-Pressure Turbine Rotor Blades

Due to the increasingly high turbine inlet temperatures, heat transfer analysis is now, more than ever, a vital part of the design and optimization of high-pressure turbine rotor blades of a modern jet engine. The present study aimed to find out how shape deviation and in-service deterioration affect heat exchange patterns on the rotor blade. The rotor geometries used for this analysis are represented by a set of high-resolution 3D structured light scans of blades with the same number of in-service hours. An automatic meshing technique was employed to generate high-resolution meshes directly on the scanned rotor geometries, which captured all the surface features with high fidelity. Steady-state 3D RANS flow simulations with a k-ω SST turbulence model were conducted on a one-and-a-half stage computational domain of the scanned geometries. First, the distribution of the heat transfer coefficient was calculated for each blade; then, a correlation was sought between the heat transfer coefficient and parametrized shape deviation, to assess the impact of each parameter on HTC levels

7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII.

Sulfocoumarins behave as interesting inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Here, we report a new series of 7-substituted derivatives which were obtained by the click chemistry approach from 7-propargyloxy-sulfocoumarin and aryl azides incorporating halogens, hydroxy, methoxy and carboxyl moieties in their molecules. The new compounds were screened for the inhibition on four physiologically relevant human CA (hCA) isoforms, the cytosolic hCA I and II and the transmembrane tumor-associated hCA IX and XII. The new compounds did not inhibit the cytosolic isoforms but were low nanomolar inhibitors of the tumor-associated ones hCA IX and XII

Synthesis of aminocyanopyrazoles via a multi-component reaction and anti-carbonic anhydrase inhibitory activity of their sulfamide derivatives against cytosolic and transmembrane isoforms

A convenient protocol for the multicomponent reaction (MCRs) between malononitrile with an orthoester and hydrazine derivatives, under acid catalyst is described. A series of aminocyanopyrazoles 4 was prepared, isolated and characterized. These pyrazoles reacted with sodium nitrite followed by secondary amine reagent and with formic acid to lead pyrazolotriazines 6 and pyrazolopyrimidinones 7. Some of the aminopyrazoles were converted to the corresponding sulfamides by reaction with sulfamoyl chloride. The aminopyrazoles incorporating phenyl and tosyl moieties were tested as inhibitors of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. Many of them showed low micromolar or submicromolar inhibition of these enzymes. The corresponding sulfamides were low nanomolar CA inhibitors

Long-lasting FR-4 surface hydrophilisation towards commercial PCB passive microfluidics

Printed circuit boards (PCB) technologies are an attractive system for simple sensing and microfluidic systems. Controlling the surface properties of PCB material is an important part of this technology and to date there has been no study on long-term hydrophilisation stability of these materials. In this work, the effect of different oxygen plasma input power and treatment duration times on the wetting properties of FR-4 surfaces was investigated by sessile droplet contact angle measurements. Super and weakly hydrophilic behaviour was achieved and the retention time of these properties was studied, with the hydrophilic nature being retained for at least 26 days. To demonstrate the applicability of this treatment method, a commercially manufactured microfluidic structure made from a multilayer PCB (3-layer FR-4 stack) was exposed to oxygen plasma at the optimum conditions. The structures could be filled with deionised (DI) water under capillary flow unlike the virgin devices

Multivalent Carbonic Anhydrases Inhibitors

Biomolecular recognition using a multivalent strategy has been successfully applied, this last decade on several biological targets, especially carbohydrate-processing enzymes, proteases, and phosphorylases. This strategy is based on the fact that multivalent interactions of several inhibitory binding units grafted on a presentation platform may enhance the binding affinity and selectivity. The zinc metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) are considered as drug targets for several pathologies, and different inhibitors found clinical applications as diuretics, antiglaucoma agents, anticonvulsants, and anticancer agents/diagnostic tools. Their main drawback is related to the lack of isoform selectivity leading to serious side effects for all pathologies in which they are employed. Thus, the multivalent approach may open new opportunities in the drug design of innovative isoform-selective carbonic anhydrase inhibitors with biomedical applications