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

Flow cytometric maturity score as a novel prognostic parameter in patients with acute myeloid leukemia

The European LeukemiaNet (ELN) classification is widely accepted for risk stratification of patients with acute myeloid leukemia (AML). In order to establish immunophenotypic features that predict prognosis, the expression of single AML blast cell antigens has been evaluated with partly conflicting results; however, the influence of immunophenotypic blast maturity is largely unknown. In our study, 300 AML patients diagnosed at our institution between January 2003 and April 2012 were analyzed. A flow cytometric maturity score was developed in order to distinguish "mature" AML (AML-ma) from "immature" AML (AML-im) by quantitative expression levels of early progenitor cell antigens (CD34, CD117, and TdT). AML-ma showed significantly longer relapse-free survival (RFS) and overall survival (OS) than AML-im (p < 0.001). Interestingly, statistically significant differences in RFS and OS were maintained within the "intermediate-risk" group according to ELN (RFS, 7.0 years (AML-ma) vs. 3.3 years (AML-im); p = 0.002; OS, 5.1 years (AML-ma) vs. 3.0 years (AML-im); p = 0.022). Our novel flow cytometric score easily determines AML blast maturity and can predict clinical outcome. It remains to be clarified whether these results simply reflect an accumulation of favorable molecular phenotypes in the AML-ma subgroup or whether they rely on biological differences such as a higher proportion of leukemia stem cells and/or a higher degree of genetic instability within the AML-im subgroup

Influencia de un injerto en el perfil de ácidos grasos y algunas propiedades fisicoquímicas de la semilla y el aceite de semillas de sandía

This study aimed to investigate the effects of grafting on the fatty acid profile and some physicochemical properties of watermelon seed and seed oil. The ‘Crimson Tide’ cultivar was used as the scion while two wild watermelon (Citrullus lanatus&nbsp;var.&nbsp;citroides&nbsp;(A1 and A2)), one&nbsp;Lagenaria siceraria&nbsp;(A3) and one&nbsp;Cucurbita maxima&nbsp;Duchesne x&nbsp;Cucurbita moschata&nbsp;Duchesne (A4) were used as rootstocks. The use of rootstock significantly influenced the fatty acid profile and the physical parameters of seeds and seed oils. The highest linoleic acid ratio was found in the seed oil from A1 and A2, the oil from A3 had the highest oleic acid ratio. The results showed that the content and acid value in seed oils were improved, and that total phenolic compounds and antioxidant activity of both seed and oil were decreased by grafting. Wild rootstocks can be used in watermelon cultivation to obtain a watermelon seed which is rich in linoleic acid.El objetivo de este estudio fue investigar los efectos del injerto en el perfil de ácidos grasos y algunas propiedades fisicoquímicas de la semilla y el aceite de semillas de sandía. El cultivar ‘Crimson Tide’ se utilizó como vástago, mientras que dos sandías silvestres (Citrullus lanatus&nbsp;var.&nbsp;Citroides&nbsp;(A1 y A2)), una&nbsp;Lagenaria siceraria&nbsp;(A3) y una&nbsp;Cucurbita maxima&nbsp;Duchesne x&nbsp;Cucurbita moschata&nbsp;Duchesne (A4) se utilizaron como portainjertos. El uso de portainjertos influyó significativamente en el perfil de ácidos grasos y los parámetros físicos de semillas y aceites de semillas. La proporción de ácido linoleico más alta se encontró en el aceite de semillas de A1 y A2, el aceite de A3 tuvo la proporción de ácido oleico más alta. Los resultados mostraron que el contenido de aceite y el índice de acidez mejoró y los compuestos fenólicos totales y la actividad antioxidante tanto de la semilla como del aceite se redujeron mediante el injerto. Para obtener un aceite de semillas de sandía rico en ácido linoleico, se pueden utilizar portainjertos silvestres en el cultivo de sandía

Optical and XPS evidence for the electrochemical generation of an N-heterocyclic carbene and its CS2 adduct from the ionic liquid [bmim][PF6]

Room temperature ionic liquids continue to be at the forefront of chemistry, covering a broad spectrum of research areas from electrochemistry and energy to catalysis and green chemistry. Therefore, it is of great value to fully understand the chemical and electrochemical reactivity and stability of ionic liquids utilized in these applications. In this context, we have investigated the electrochemical generation of an N-heterocyclic carbene and its CS2 adduct from the ionic liquid [bmim][PF6], and X-ray photoelectron spectroscopy (XPS) proved to be a highly effective spectroscopic tool to study such systems. Initially, the dithiocarboxylate adduct was chemically synthesized as a reference compound starting from both [bmim][PF6] and [bmim][OAc], and characterized by HRMS, and 1H- and 13C-NMR, FTIR, visible and X-ray photoelectron spectroscopy. While a simple mixture of [bmim][PF6] and CS2 revealed no evidence of adduct formation, the application of an electrochemical stimulus led to the formation of the dithiocarboxylate adduct as evidenced optically and through the newly formed S2p peak in the XP spectrum. Further evidence for the electrochemical reduction of [bmim][PF6] to the corresponding N-heterocyclic carbene came from the XPS analysis via the appearance of a new N1s peak in the XP spectrum. © 2017 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique

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

Učinak formulacijskih parametara na oslobađanje lijeka i svojstva dvoslojnih tableta koje plutaju u želucu

Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanism.U radu su opisane plutajuće tablete acetilsalicilne kiseline za antikoagulacijsku upotrebu s produljenim zadržavanjem u želucu i većom bioraspoloživošću. Plutajući dio tih dvoslojnih tableta sadržavao je hidroksipropil metilcelulozu (HPMC) visoke viskoznosti i efervescentnu smjesu limunske kiseline i natrijevog hidrogenkarbonata. Drugi sloj sadržavao je ljekovitu tvar, sredstvo za izravno tabletiranje i različite vrste matriksnog polimera poput HPMC niske viskoznosti, natrij-karboksimetilceluloze i kitozana. Tablete su pripravljene metodom izravne kompresije. Ispitivan je utjecaj formulacijskih varijabli na fizikokemijska i plutajuća svojstva, te oslobađanje ljekovite tvari. Plutajuća svojstva ovise o količini efervescentnih tvari i gelirajućeg polimera u plutajućem sloju. Promjenom vrste i viskoznosti polimera u matriksnom sloju s lijekom produljeno je oslobađanje ljekovite tvari na 8 sati. Iz svih formulacija ljekovita tvar oslobađala se difuzijom

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

A conserved long-distance telomeric silencing mechanism suppresses mTOR signaling in aging human fibroblasts

Telomeres are repetitive nucleotide sequences at the ends of each chromosome. It has been hypothesized that telomere attrition evolved as a tumor suppressor mechanism in large long-lived species. Long telomeres can silence genes millions of bases away through a looping mechanism called telomere position effect over long distances (TPE-OLD). The function of this silencing mechanism is unknown. We determined a set of 2322 genes with high positional conservation across replicatively aging species that includes known and candidate TPE-OLD genes that may mitigate potentially harmful effects of replicative aging. Notably, we identified PPP2R2C as a tumor suppressor gene, whose up-regulation by TPE-OLD in aged human fibroblasts leads to dephosphorylation of p70S6 kinase and mammalian target of rapamycin suppression. A mechanistic link between telomeres and a tumor suppressor mechanism supports the hypothesis that replicative aging fulfills a tumor suppressor function and motivates previously unknown antitumor and antiaging strategies

The opportunities and the limitations of using the independent post-editor technology in translation education

A new mechanical function known as post-editing, which helps to correct the imperfections of raw machine translation output, is introduced in the translation market. While this function is commonly used as an integral part of the machine translation, it can also be used for correcting non-translated texts on its own. The main purpose of this study is to find an answer to the question of which contributions could be made to the competences of translation students by using independent post-editors during academic translation education. A model course application and survey are conducted with the participation of students from translation studies departments. The interrater reliability is used in this study. In accordance with the results, it is found that most of the students have not known the usage of the independent post-editors during the translation process. The research provides new insights into the contributions of post-editor technology to the translation education. The findings of the research also reflect the contributions of post-editor technology to the translation quality in terms of the speed-time management, the accuracy of punctuations, abbreviations, and grammar rules. It is also determined that the post-editors contribute to the competencies of the translation students. As a result, it is suggested that the post-editors may be used as an educational material in translation education. Indeed, the results require other studies about the usage of post-editors as educational materials. © 2018 The Science and Information (SAI) Organization Limited