Synthesis of Novel Nitroxoline Analogs with Potent Cathepsin B Exopeptidase Inhibitory Activity

Nitroxoline, a well-known antimicrobial agent, has been identified in several independent studies, and on different molecular targets, as a promising candidate to be repurposed for cancer treatment. One specific target of interest concerns cathepsin B, a lysosomal peptidase involved in the degradation of the extracellular matrix (ECM), leading to tumor invasion, metastasis and angiogenesis. However, dedicated optimization of the nitroxoline core is needed to actually deliver a nitroxoline-based antitumor drug candidate. Within that context, 34 novel nitroxoline analogs were synthesized and evaluated for their relative cathepsin B inhibitory activity, their antiproliferative properties and their antimicrobial activity. More than twenty analogs were shown to exert a similar or even slightly higher cathepsin B inhibitory activity compared to nitroxoline. The implemented modifications of the nitroxoline scaffold and the resulting SAR information can form an eligible basis for further optimization toward more potent cathepsin B inhibitors in the quest for a clinical nitroxoline-based antitumor agent.     

Alumina-Protected,Durable and Photostable Zinc Sulfide Particles from Scalable Atomic Layer Deposition

Zinc sulfide has unique and easily modifiable photophysical properties and is a promising candidate for photocatalysis and optoelectronic devices. However, ZnS suffers from corrosive decomposition during excitation processes like UV irradiation, which drastically limits its field of potential applications. For the first time, complete photostabilization of individual ZnS particles by a dense, durable, and only 3-nm-thick Al₂O₃ layer, produced by rotary atomic layer deposition (ALD) is reported. In contrast to bare ZnS, the coated particles do not suffer from photocorrosive degradation even under long-term or high power UV irradiation. The presence of a protection layer covering the entire ZnS surface is additionally confirmed by microscopic and spectroscopic investigations of particle cross-sections. Further, complete inhibition of the reaction between Ag⁺ ions added as the analyte and the ZnS surface is observed. Durability tests of the as-prepared Al₂O₃ layer upon prolonged exposure to water reveal a significant decrease in the protection capability of the layer, which is ascribed to the hydrolysis of the amorphous Al₂O₃. A calcination step at 1000 °C after the ALD treatment, which leads to crystallization of the amorphous Al₂O₃ layer, successfully suppresses this hydrolysis and produces an insulating, dense, and inert protection layer.     

Identification of boundary heat fluxes in a falling film experiment using high resolution temperature measurements

In this paper, we consider a three-dimensional inverse heat conduction problem (IHCP) in a falling film experiment. The wavy film is heated electrically by a thin constantan foil and the temperature on the back side of this foil is measured by high resolution infrared (IR) thermography. The transient heat flux at the inaccessible film side of the foil is determined from the IR data and the electrical heating power. The IHCP is formulated as a mathematical optimization problem, which is solved with the conjugate gradient method. In each step of the iterative process two direct transient heat conduction problems must be solved. We apply a one step θ-method and piecewise linear finite elements on a tetrahedral grid for the time and space discretization, respectively. The resulting large sparse system of equations is solved with a preconditioned Krylov subspace method. We give results of simulated experiments, which illustrate the performance and tuning of the solution method, and finally present the estimation results from temperature measurements obtained during falling film experiments.     

In‐Situ Switching from Barrier‐Limited to Ohmic Anodes for Efficient Organic Optoelectronics

Injection and extraction of charges through ohmic contacts are required for efficient operation of semiconductor devices. Treatment using polar non‐solvents switches polar anode surfaces, including PEDOT:PSS and ITO, from barrier‐limited hole injection and extraction to ohmic behaviour. This is caused by an in‐situ modification of the anode surface that is buried under a layer of organic semiconductor. The exposure to methanol removes polar hydroxyl groups from the buried anode interface, and permanently increases the work function by 0.2–0.3 eV. In the case of ITO/PEDOT:PSS/PBDTTT‐CT:PC71BM/Al photovoltaic devices, the higher work function promotes charge transfer, leading to p‐doping of the organic semiconductor at the interface. This results in a two‐fold increase in hole extraction rates which raises both the fill factor and the open‐circuit voltage, leading to high power conversion efficiency of 7.4%. In ITO/PEDOT:PSS/F8BT/Al polymer light‐emitting diodes, where the organic semiconductor's HOMO level lies deeper than the anode Fermi level, the increased work function enhances hole injection efficiency and luminance intensity by 3 orders of magnitude. In particular, hole injection rates from PEDOT:PSS anodes are equivalent to those achievable using MoO₃. These findings exemplify the importance of work function control as a tool for improved electrode design, and open new routes to device interfacial optimization using facile solvent processing techniques. Such simple, persistent, treatments pave the way towards low cost manufacturing of efficient organic optoelectronic devices.     

Localized high-rate deposition of zinc oxide films at atmospheric pressure using inductively coupled microplasma

Linear transparent zinc oxide films were fabricated using an inductively coupled microplasma jet generated in argon under atmospheric conditions. The films were formed by the sputtering and melting of a zinc filament placed inside the plasma. Film growth rates varied between 10 to 30 nm/s for input powers between 20 and 30 W. Film roughness below 20 nm and optical transmittances up to 90% in the visible were obtained while the sheet resistances ranged between 2 × 10⁴ and 1 × 10⁵Ω/□. The presented technique may allow high-rate, localized, fabrication of functional ZnO films for optoelectronic applications.     

A two species trap for chromium and rubidium atoms

Abstract

We realize a combined trap for bosonic chromium (⁵²Cr) and rubidium (⁸⁷Rb) atoms. Initial experiments focus on exploring a suitable loading scheme for the combined trap and on studies of new trap loss mechanisms originating from simultaneous trapping of two species. By comparing the trap loss from the ⁸⁷Rb magneto-optical trap (MOT) in the absence and presence of magnetically trapped ground state ⁵²Cr atoms we determine the scattering cross-section of σ _inel,RbCr = 5.0 ± 4.0 × 10^?18 m² for light-induced inelastic collisions between the two species. Studying the trap loss from the Rb magneto-optical trap induced by the Cr cooling-laser light, the photoionization cross-section of the excited 5P_3/1 state at an ionizing wavelength of 426 nm is measured to be σ _P = 1.1 ± 0.3 × 10^?21 m².     

Influence of the substrate finish and thin film roughness on the optical performance of Mo/Si multilayers

Scattering resulting from interface imperfections critically affects the image contrast and optical throughput of multilayer coatings for 13.5 nm. To investigate the scattering mechanisms, at-wavelength scattering measurements in combination with atomic force microscopy are analyzed for an in-depth characterization of the roughness properties. The different impacts of substrate finish and intrinsic thin film roughness on the scattering distribution are separated and analyzed in detail. Furthermore, a novel approach to characterize the roughness of large extreme ultraviolet substrates is presented, based on light scattering measurements at 442 nm.     

Moving toward seamless mobility: state of the art and emerging aspects in standardization bodies

The challenge to provide seamless mobility in the near future emerges as a key topic in various standardization bodies. This includes first of all the support of seamless handover between homogeneous networks. Distinct technologies—such as IEEE 802.11WLANs (Wi-Fi) and IEEE 802.16 MANs WiMAX—have recently augmented such support to existing standards to enable seamless homogeneous handover. Cellular networks, in contrast, already included this inherently from the start. Currently considerable effort goes into coupling of different radio access technologies. Therefore, the second key topic in standardization is seamless heterogeneous handovers. IEEE, IETF, as well as 3GPP consider different approaches toward architectures and protocols enabling seamless mobility management. In this work, we discuss recent and on-going standardization activities within IEEE, IETF, and 3GPP toward seamless homogeneous as well as heterogeneous mobility support.     

Observation and characterization of defects in HfO2 high-K gate dielectric layers

A deeper understanding of Hf-based high-K materials in terms of their structural and electrical defects is important for device implementation. We have studied the occurrence of such defects using wet-etch defect delineation, electron microscopy, depth-profiling and conventional electrical measurements. It is evident that defects are present in HfO₂ films that are related to the microstructure and stoichiometry of the film, which in turn depend on the deposition temperature, starting surface and post-deposition treatments. These results appear to be independent of the deposition technique. Two types of defects were observed, those that are physically visible and cause immediate failures especially on large-area structures, and those that cause high leakage but not immediate failures. The existence of defects affects not only leakage or performance but will also affect the reliability through trapping of charge at the defect sites. As films continue to be scaled thinner, the requirements on defect reduction to minimize electrical impact may become more stringent.