Synthesis, modeling, and biological evaluation of anti-tubulin indole-substituted furanones.

Due to the central role of tubulin in various cellular functions, it is a validated target for anti-cancer therapeutics. However, many of the current tubulin inhibitors are derived from complex natural products and suffer from multidrug resistance, low solubility, toxicity issues, and/or the lack of multi-cancer efficacy. As such, there is a continued need for the discovery and development of new anti-tubulin drugs to enter the pipeline. Herein we report on a group of indole-substituted furanones that were prepared and tested for anti-cancer activity. Molecular docking studies showed positive correlations between favorable binding in the colchicine binding site (CBS) of tubulin and anti-proliferative activity, and the most potent compound was found to inhibit tubulin polymerization. These compounds represent a promising new structural motif in the search for small heterocyclic CBS cancer inhibitors.

Detection of Toxoplasma gondii oocysts on organic and conventionally grown produce.

Toxoplasma gondii infection can result in toxoplasmosis and potential psychological effects. Research commonly focuses on infection through contact with cat fecal matter or consumption of contaminated meat. However, T. gondii oocysts can persist in the environment for years and may be present in soils and on soil-grown produce. Rates of oocyst DNA recovery from produce were high, with 18% of vegetable samples testing positive for T. gondii via PCR test and melt curve analysis. Radishes had significantly higher oocyst counts than arugula, collard greens, kale, lettuce, and spinach. There were no significant differences in oocyst detection rates between samples taken from organic farmer's markets and conventional grocery stores. This study demonstrates that these oocysts can transfer to produce grown both conventionally and using organic techniques.

Burden of illness for patients with cholangiocarcinoma in the United States: a retrospective claims analysis.

BACKGROUND: Advanced cholangiocarcinoma (CCA) is associated with considerable morbidity and mortality. Novel second-line treatments for advanced CCA underscore the need to understand treatment patterns and economic burden of illness in clinical practice. METHODS: This retrospective, claims-based study using Optum's de-identified Clinformatics® Data Mart Database [2007-2019] selected patients with CCA who experienced failure of a line of therapy containing either gemcitabine or fluorouracil. The index date was defined based on evidence of treatment failure: date of last administration of the gemcitabine- or fluorouracil-based regimen plus 28 days, or initiation date of the next-line systemic therapy. Treatment patterns, healthcare resource use (HRU), costs, and survival were assessed during the follow-up period (index until death or end of eligibility). RESULTS: A total of 1,298 patients met inclusion criteria and had a mean age of 69.1 years. There were 958 patients (73.8%) with intrahepatic and 275 patients (21.2%) with extrahepatic CCA. Average follow-up was 7.5 months. Almost 40% of patients did not receive another line of therapy after the index date. Among the 784 patients who received another line of therapy, 40.3% used fluorouracil-based therapy, 30.7% used gemcitabine-based therapy, and 29.3% used capecitabine-based therapy. Total mean per patient per month CCA-related healthcare costs were $7,743, with medical services ($6,685) a larger driver of monthly costs relative to treatment costs ($1,058). Median overall survival (OS) was 5.3 months among all patients. CONCLUSIONS: Many patients with advanced CCA do not initiate additional therapy after failure of gemcitabine or fluorouracil treatment, and there is considerable variation in treatments among those who do. This study highlights the high costs and unmet need for a standard of care in this patient population.

Discovery of an indole-substituted furanone with tubulin polymerization inhibition activity.

Analogs of diarylpyrrolinone lead compound 1 were prepared and tested for anti-proliferative activity in U-937 cancer cells. Alterations of 1 focused on modifying the two nitrogen atoms: a) the pyrrolinone nitrogen atom was substituted with a propyl group or replaced with an oxygen atom (furanone), and b) the substituents on the indole nitrogen were varied. These changes led to the discovery of a furanone analog 3b with sub-micromolar anti-cancer potency and tubulin polymerization inhibition activity.

Investigation of the Internal Structure of a Modern Seafloor Hydrothermal Chimney With a Combination of EBSD, EPMA, and XRD.

Samples from the sphalerite-dominated zone of a seafloor massive sulfide chimney, the Satanic Mills Chimney of the PACMANUS hydrothermal field, have been investigated to determine the internal macrostructure and microstructure of this zone, the phases present, and the distribution of metals. A combination of electron probe microanalysis, electron backscattered diffraction, and x-ray diffraction has been used. At the macroscale, this zone of the chimney wall is heavily porous and is comprised primarily of sphalerite, enclosing minor chalcopyrite, pyrite, and wurtzite. A Pb­As sulfosalt layer of possible microbial origins is present at the outer edge of the sphalerite matrix, next to a pore. The sphalerite has grown in globules on the order of 300 µm in diameter. At the microscale, the sphalerite features a colloform texture and a duplex-type grain structure consisting of either fine-grain regions in the center surrounded by coarse-grained regions or radiating coarse grains only. Pb- and As-rich bands have been detected in the colloform sphalerite, and growth twins have been observed in both the sphalerite and chalcopyrite crystals. A qualitative description of the growth of a typical globule is given, including nucleation, crystal growth, and solute redistribution.

Incorporation of γ-butyrolactone (GBL) dramatically lowers the phase transition temperature of formamidinium-based metal halide perovskites.

We demonstrate that the δ to α phase transition temperature of formamidinium-based perovskites is reduced by ∼50 °C through the incorporation of ∼2 wt% γ-butyrolactone (GBL) into the crystal lattice. The intercalation of GBL is found to expand the unit cell of the δ-phase, reducing the energy barrier for thermal conversion.

A flow cell for the study of gas-solid reactions via in situ powder X-ray diffraction.

This paper describes the development and testing of a novel capillary flow cell for use in in situ powder X-ray diffraction experiments. It is designed such that it achieves 200° of rotation of the capillary whilst still allowing the flow of gas through the sample and the monitoring of off gas via mass spectrometry, gas chromatography, or other such analytical techniques. This high degree of rotation provides more uniform heating of the sample than can be achieved in static cells or those with lower rotational ranges and consequently also improves particle statistics. The increased uniformity of heating provides more accurate temperature calibration of the experimental setup as well. The cell is designed to be held in a standard goniometer head and is therefore suitable for use in many laboratory and synchrotron instruments.

Vacancy Generation and Oxygen Uptake in Cu-Doped Pr-CeO2 Materials using Neutron and in Situ X-ray Diffraction.

The oxygen uptake ability of Pr-CeO2-based oxygen carriers, catalysts, and solid oxide fuel cells can be attributed to 3+ cation generation and the presence of vacant oxygen sites. Oxygen occupancies of CeO2, Pr-CeO2, and 5% Cu-doped Pr-CeO2 were investigated using neutron diffraction and related to the oxygen uptake as determined using thermogravimetric analysis (TGA). The presence of vacant tetrahedral oxygen sites at room temperature did not correspond to low-temperature oxygen uptake. The materials did not uptake oxygen at 420 °C, but oxygen uptake was observed at 600 °C, which indicated that a minimum temperature needs to be met to generate sufficient vacancies/3+ cations. Variations in the lattice parameter as a function of temperature were revealed using in situ X-ray diffraction (XRD). With increasing temperature the lattice parameter increased linearly due to thermal expansion and was followed by an exponential increase at ∼300-400 °C as cations were reduced. Despite segregation of Cu into CuO at high dopant concentration, at 600 °C a higher O2 uptake was obtained for Ce0.65Pr0.20Cu0.15O2-δ (120 µmol g-1), in comparison to Ce0.75Pr0.2Cu0.05O2-δ (92 µmol g-1), and was higher than that for Ce0.8Pr0.2O2-δ (55 µmol g-1). Both Pr and Cu introduce vacancies and promote the O2 uptake of CeO2.

In situ synchrotron X-ray diffraction investigation of the evolution of a PbO2/PbSO4 surface layer on a copper electrowinning Pb anode in a novel electrochemical flow cell. Corrigendum.

Figures 7 and 8 of the article by Clancy et al. [(2015), J. Synchrotron Rad. 22, 366-375] are corrected.

In situ synchrotron X-ray diffraction investigation of the evolution of a PbO2/PbSO4 surface layer on a copper electrowinning Pb anode in a novel electrochemical flow cell.

This paper describes the quantitative measurement, by in situ synchrotron X-ray diffraction (S-XRD) and subsequent Rietveld-based quantitative phase analysis and thickness calculations, of the evolution of the PbO2 and PbSO4 surface layers formed on a pure lead anode under simulated copper electrowinning conditions in a 1.6 M H2SO4 electrolyte at 318 K. This is the first report of a truly in situ S-XRD study of the surface layer evolution on a Pb substrate under cycles of galvanostatic and power interruption conditions, of key interest to the mining, solvent extraction and lead acid battery communities. The design of a novel reflection geometry electrochemical flow cell is also described. The in situ S-XRD results show that ß-PbO2 forms immediately on the anode under galvanostatic conditions, and undergoes continued growth until power interruption where it transforms to PbSO4. The kinetics of the ß-PbO2 to PbSO4 conversion decrease as the number of cycles increases, whilst the amount of residual PbO2 increases with the number of cycles due to incomplete conversion to PbSO4. Conversely, complete transformation of PbSO4 to ß-PbO2 was observed in each cycle. The results of layer thickness calculations demonstrate a significant volume change upon PbSO4 to ß-PbO2 transformation.

Low-Loss Optical Waveguides for the Near Ultra-Violet and Visible Spectral Regions with Al(2)O(3) Thin Films from Atomic Layer Deposition.

In this work, we report low-loss single-mode integrated optical waveguides in the near ultra-violet and visible spectral regions with aluminum oxide (Al(2)O(3)) films using an atomic layer deposition (ALD) process. Alumina films were deposited on glass and fused silica substrates by the ALD process at substrate/chamber temperatures of 200 °C and 300 °C. Transmission spectra and waveguide measurements were performed in our alumina films with thicknesses in the range of 210 - 380 nm for the optical characterization. Those measurements allowed us to determine the optical constants (n(w) and k(w)), propagation loss, and thickness of the alumina films. The experimental results from the applied techniques show good agreement and demonstrate a low-loss optical waveguide. Our alumina thin-film waveguides is well transparent in the whole visible spectral region and also in an important region of the UV; the measured propagation loss is below 4 dB/cm down to a wavelength as short as 250 nm. The low propagation loss of these alumina guiding films, in particular in the near ultra-violet region which lacks materials with high optical performance, is extremely useful for several integrated optic applications.

A flow cell for in situ synchrotron x-ray diffraction studies of scale formation under Bayer processing conditions.

The design, construction, and commissioning of a stainless steel flow cell for in situ synchrotron x-ray diffraction studies of scale formation under Bayer processing conditions is described. The use of the cell is demonstrated by a study of Al(OH)(3) scale formation on a mild steel substrate from synthetic Bayer liquor at 70 degrees C. The cell design allows for interchangeable parts and substrates and would be suitable for the study of scale formation in other industrial processes.