Structural motifs of pre-nucleation clusters

Structural motifs of pre-nucleation clusters prepared in single, optically levitated supersaturated aqueous aerosol microparticles containing CaBr2 as a model system are reported. Cluster formation is identified by means of X-ray absorption in the Br K-edge regime. The salt concentration beyond the saturation point is varied by controlling the humidity in the ambient atmosphere surrounding the 15–30 μm microdroplets. This leads to the formation of metastable supersaturated liquid particles. Distinct spectral shifts in near-edge spectra as a function of salt concentration are observed, in which the energy position of the Br K-edge is red-shifted by up to 7.1 ± 0.4 eV if the dilute solution is compared to the solid. The K-edge positions of supersaturated solutions are found between these limits. The changes in electronic structure are rationalized in terms of the formation of pre- nucleation clusters. This assumption is verified by spectral simulations using first-principle density functional theory and molecular dynamics calculations, in which structural motifs are considered, explaining the experimental results. These consist of solvated CaBr2 moieties, rather than building blocks forming calcium bromide hexahydrates, the crystal system that is formed by drying aqueous CaBr2 solutions

Cost-effectiveness of sorafenib for treatment of radioactive iodine (rai)-refractory locally advanced/metastatic differentiated thyroid cancer (dtc) in Turkey

WOS: 000354498503198OBJECTIVES: Sorafenib is the first product approved for treatment of RAI refractory locally advanced/metastatic DTC patients. This study was conducted in order to analyze cost-effectiveness of sorafenib for treatment of patients with RAI refractory locally advanced/metastatic DTC in Turkey. METHODS: A cohort partition model assigning patients to one of three health states according to the proportion of patients who are progression-free, progressed, or dead in each 28-days cycle was adapted to Turkish setting. The incremental cost-effectiveness ratios (ICER) were calculated per quality-adjusted life years (QALYs) and life-years (LYs) gained. Turkish payer’s perspective was taken and time-horizon was set as patient’s lifetime (maximum 30 years). Sorafenib was compared to the best supportive care (BSC) within the model since there are no agents for treatment of patients on this stage of the disease. Essential clinical inputs were derived from DECISION trial and local resource-utilization data were based on expert opinions through an expert panel. Sensitivity of the results was evaluated in terms of key inputs by deterministic oneway and probabilistic sensitivity analyses. All costs were calculated in Turkish Liras (TL) and converted to USD using TL/USD currency rate as 2.2 (mid-2014). RESULTS: Total cost of sorafenib-treated patients is 24,384 USD higher compared to BSC. Besides, sorafenib is associated with increments of 1.29 LYs and 0.80 QALYs compared to BSC. The ICER of sorafenib per LYs and QALYs gained compared to BSC were determined as 18,851 USD and 30,485 USD respectively. One-way sensitivity analysis demonstrated that results are not sensitive to the changes in model inputs and pharmacoeconomic analysis results were validated by probabilistic sensitivity analysis. CONCLUSIONS: Sorafenib is cost-effective for treatment of patients with RAI refractory locally advanced/metastatic DTC compared to BSC with an ICER value below the willingness-to-pay threshold (3-times GDP per capita ─ 32,346 USD) for Turkey

Distance laboratory applications ERRL: A study on radio communication in electronic field

In the last decade, the effect of internet usage in education is gradually increased. When we look from academic perspective, the new technologies provided alternatives for students learning. As distance education becomes important everyday, the indispensable elements of teaching and education, laboratories must be reachable via remote connection. Consequently, the education that is going to be given to the students will be more flexible with respect to place and time constraints and students can reach laboratory facilities at any time and anywhere not only in lectures and practical hours. In this study, European Remote Radio Laboratory (ERRL) which is a distance remote Radio Frequency (RF) laboratory designed for electrical-electronics students, is described generally. The software architecture, infrastructure and experiment that can be done with a remote connection have been described

CA8 Mutations Cause a Novel Syndrome Characterized by Ataxia and Mild Mental Retardation with Predisposition to Quadrupedal Gait

We describe a consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. Genome-wide linkage analysis identified a 5.8 Mb interval on chromosome 8q with shared homozygosity among the affected persons. Sequencing of genes contained in the interval revealed a homozygous mutation, S100P, in carbonic anhydrase related protein 8 (CA8), which is highly expressed in cerebellar Purkinje cells and influences inositol triphosphate (ITP) binding to its receptor ITPR1 on the endoplasmatic reticulum and thereby modulates calcium signaling. We demonstrate that the mutation S100P is associated with proteasome-mediated degradation, and thus presumably represents a null mutation comparable to the Ca8 mutation underlying the previously described waddles mouse, which exhibits ataxia and appendicular dystonia. CA8 thus represents the third locus that has been associated with quadrupedal gait in humans, in addition to the VLDLR locus and a locus at chromosome 17p. Our findings underline the importance of ITP-mediated signaling in cerebellar function and provide suggestive evidence that congenital ataxia paired with cerebral dysfunction may, together with unknown contextual factors during development, predispose to quadrupedal gait in humans

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results

Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements

Sterically hindered N-aryl/benzyl substituted piperidoimidazolin-2-ylidene palladium complexes and their catalytic activities

A series of N-aryl (2a,b) or benzyl (2c,d) substituted piperidoimidazolinium salts and their palladium complexes (3a-d) were prepared and characterized by 1H, 13C NMR, IR spectroscopy and elemental analysis. The crystal structures of 3a and 3c have been determined by X-ray crystallography. Thermogravimetric analysis (TGA) was applied to complexes (3a–d). The palladium complexes have been employed as catalyst for Suzuki-Miyaura cross coupling. The N-aryl substituted complex 3b was a highly efficient precatalyst and successfully employed in Suzuki-Miyaura cross coupling reactions of (hetero)aryl chlorides with arylboronic acids in air. In addition, the oxidative addition step of the reaction mechanism involving chlorobenzene and the catalysts 3a, 3b, 3c and 3d were computationally investigated by the DFT-?-B97X-D method and complete agreement were obtained with the catalytic results. To measure ?-donating and ?-acceptor properties of the new ligands, the rhodium carbonyl complexes were also prepared. © 2018 Elsevier Ltd2010 2010- Fen-076, 2010-FEN -046All calculations reported in this paper were performed at High Performance and Grid Computing Center (TRUBA resources), ULAKBIM. The authors also acknowledge Dokuz Eylul University for the use of the Agilent Xcalibur Eos diffractometer (purchased under University Research Grant no. 2010.KB.FEN.13 ). Financial support from Ege University (project 2010-FEN -046 and 2010- Fen-076 ) is gratefully acknowledged. Appendix A -