Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor

The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small-molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine-based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.     

Crystal Structure and Elastic Properties of Hypothesized MAX Phase‐Like Compound (Cr2Hf)2Al3C3

The term “MAX phase” refers to a very interesting and important class of layered ternary transition‐metal carbides and nitrides with a novel combination of both metal and ceramic‐like properties that have made these materials highly regarded candidates for numerous technological and engineering applications. Using (Cr₂Hf)₂Al₃C₃ as an example, we demonstrate the possibility of incorporating more types of elements into a MAX phase while maintaining the crystallinity, instead of creating solid solution phases. The crystal structure and elastic properties of MAX phase‐like (Cr₂Hf)₂Al₃C₃ are studied using the Vienna ab initio Simulation Package. Unlike MAX phases with a hexagonal symmetry (P6₃/mmc, #194), (Cr₂Hf)₂Al₃C₃ crystallizes in the monoclinic space group of P2₁/m (#11) with lattice parameters of a = 5.1739 Å, b = 5.1974 Å, c = 12.8019 Å; α = β = 90°, γ = 119.8509°. Its structure is found to be energetically much more favorable with an energy (per formula unit) of ?102.11 eV, significantly lower than those of the allotropic segregation (?100.05 eV) and solid solution (?100.13 eV) phases. Calculations using a stress versus strain approach and the VRH approximation for polycrystals also show that (Cr₂Hf)₂Al₃C₃ has outstanding elastic moduli.     

Through‐the‐glass spectroscopic ellipsometry for analysis of CdTe thin‐film solar cells in the superstrate configuration

Polycrystalline CdS/CdTe thin‐film solar cells in the superstrate configuration have been studied by spectroscopic ellipsometry (SE) using glass side illumination. In this measurement method, the first reflection from the ambient/glass interface is rejected, whereas the second reflection from the glass/film‐stack interface is collected; higher order reflections are also rejected. The SE analysis incorporates parameterized dielectric functions ε for solar cell component materials obtained by in situ and variable‐angle SE. In the SE analysis of the complete cells, a step‐wise procedure ranks the fitting parameters, including thicknesses and those defining the spectra in ε, according to their ability to reduce the root‐mean‐square deviation between the simulated and measured SE spectra. The best fit thicknesses from this analysis are found to be consistent with electron microscopy. Based on the SE results, the solar cell quantum efficiency (QE) can be simulated without any free parameters, and comparisons with measured QE enable optical model refinements as well as identification of optical and electronic losses. These capabilities have wide applications in photovoltaic module mapping and in‐line monitoring. Copyright © 2016 John Wiley & Sons, Ltd.     

Radiolabeled Polymeric Nanoconstructs Loaded with Docetaxel and Curcumin for Cancer Combinatorial Therapy and Nuclear Imaging

Growing evidence suggests that multifaceted diseases as cancer can be effectively tackled by hitting simultaneously different biological targets and monitoring patient‐specific responses. Combinatorial therapies, relying on the administration of two or more molecules with different cytotoxic mechanisms, are rapidly progressing in the clinic. Here, 100 nm spherical polymeric nanoconstructs (SPNs) are proposed for the combinatorial treatment of tumors by codelivering a potent antimitotic drug—docetaxel (DTXL)—and a broad spectrum anti‐inflammatory molecule—curcumin (CURC). In vitro, SPNs loaded with DTXL and CURC induce a threefold decrease in IC₅₀ as compared to DTXL‐loaded SPNs. This synergic antitumor effect is also significant in mouse models of glioblastoma multiforme, where, after 22 d of treatment, the combinatorial approach leads to complete disease regression. At 90 d post‐treatment initiation, mice injected with DTXL + CURC SPNs have a 100% survival, whereas only 50% of the DTXL SPN treated mice survive. SPNs are also labeled with radioactive ⁶⁴Cu(DOTA) molecules to document, via PET imaging, the progressive tumor mass shrinkage. Sensitization of DTXL by CURC is associated with NF‐κB downregulation and increased apoptosis. These theranostic nanoconstructs could be used for combinatorial treatment and assessment of therapeutic efficacy in other malignancies.     

Hydrous iron oxide for removal of inorganic contaminants in simulated stormwater: A batch sorption kinetics study

Urban stormwater runoff, which consists of inorganic and organic contaminants, is a major source of pollutants to receiving waters and therefore they need to be removed. Simultaneous removal of contaminants, Cd²⁺, Cu²⁺, Ni²⁺, Zn²⁺ (heavy metal cations), and SeO₄²⁻ (oxyanion) from a simulated stormwater by a hydrous ferric oxide (HFO) was studied in batch and column sorption experiments. In the batch experiment the rate of sorption of the ions was rapid at the beginning and reached equilibrium in approximately 300 min. The amounts of ions sorbed were proportionate to the respective initial concentration of the ions added to the HFO. Cluster analysis showed that all heavy metals had similar sorption behavior, whereas Se had a distinctly different sorption process. Of the three different kinetic models tested the pseudo-first order kinetic model fitted the data the best. The column experimental results beyond 180 min were consistent with those of the batch experiment that the removal efficiencies of the ions were in proportion to the ion concentration in the feed. Below 180 min, Cu appeared to be preferentially removed than Zn.     

Hierarchically Structured Magnetic Nanoconstructs with Enhanced Relaxivity and Cooperative Tumor Accumulation

Iron oxide nanoparticles are formidable multifunctional systems capable of contrast enhancement in magnetic resonance imaging, guidance under remote fields, heat generation, and biodegradation. Yet, this potential is underutilized in that each function manifests at different nanoparticle sizes. Here, sub‐micrometer discoidal magnetic nanoconstructs are realized by confining 5 nm ultra‐small super‐paramagnetic iron oxide nanoparticles (USPIOs) within two different mesoporous structures, made out of silicon and polymers. These nanoconstructs exhibit transversal relaxivities up to ≈10 times (r ₂ ≈ 835 mm ^?1 s^?1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r ₂ relaxivity arises from the formation of mesoscopic USPIO clusters within the porous matrix, inducing a local reduction in water molecule mobility as demonstrated via molecular dynamics simulations. The cooperative accumulation under static magnetic field derives from the large amount of iron that can be loaded per nanoconstuct (up to ≈65 fg) and the consequential generation of significant inter‐particle magnetic dipole interactions. In tumor bearing mice, the silicon‐based nanoconstructs provide MRI contrast enhancement at much smaller doses of iron (≈0.5 mg of Fe kg^?1 animal) as compared to current practice.     

Formation of Nanocrystalline Calcia by the Decomposition of Calcite

Formation of nanocrystalline calcia from calcite has been studied in situ via transmission electron microscopy. The crystallographic transformation occurred via two mechanisms: the first is by distortion of the cleaved rhombohedron of calcite, formed by {104} planes in hexagonal coordinates, into a cube. This produced a microstructure of oriented, elongated nanocrystals of calcia with planar boundaries. In the second mechanism, the micrometer-sized parent calcite particles broke up into nano-sized grains as the decomposition began, leading to irregularly shaped, randomly oriented nanocrystals of calcia.     

Effect of substrate bias voltage on the properties of diamond-like carbon thin films deposited by microwave surface wave plasma CVD

Diamond-like carbon (DLC) thin films were deposited on silicon and ITO substrates with applying different negative bias voltage by microwave surface wave plasma chemical vapor deposition (MW SWP-CVD) system. The influence of negative bias voltage on optical and structural properties of the DLC film were investigated using X-ray photoelectron spectroscopy, UV/VIS/NIR spectroscopy, Fourier transform infrared spectroscopy and Raman spectroscopy. Optical band gap of the films decreased from 2.4 to 1.7 with increasing negative bias voltage (0 to − 200 V). The absorption peaks of sp³ CH and sp² CH bonding structure were observed in FT-IR spectra, showing that the sp²/sp³ ration increases with increasing negative bias voltage. The analysis of Raman spectra corresponds that the films were DLC in nature.     

Stability and Mobility of Sand-Bed Channels Affected by Seepage

Seepage effects on the stability, mobility, and incipient motion of sand-bed particles are experimentally investigated. Seepage through a sand bed in a downward direction (suction) reduces the stability of particles, and it can even initiate their movement. The bed erosion is increased with the increased rates of suction. Whereas the seepage in an upward direction (injection) increases the stability of bed particles, it does not aid initiating their movement. The rate of bed erosion is reduced or even stopped by the increased injection rates. Hydrodynamic conditions leading to the so-called “pseudoincipient motion” with suction (for the initiation of particles movement that are otherwise at rest under no-seepage conditions), and with injection (for only arresting the particles movement that are otherwise moving initially) are evaluated. The conventional Shields curve cannot be used to predict such pseudoincipient motion conditions with seepage. The concepts thus developed are useful for a better understanding of the sediment transport mechanics and in the design of stable alluvial channels affected by seepage.