High-resolution melting assay for genotyping of IFNL4-associated dinucleotide variant rs368234815

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Asymmetric Hydrogenation vs Transfer Hydrogenation in the Reduction of Cyclic Imines

A comparison between the two most common reduction approaches for obtaining chiral amines, asymmetric hydrogenation (AH) versus asymmetric transfer hydrogenation (ATH), was accomplished by using iridium complexes based on atropoisomeric diphosphines and cyclic diamines as ligands respectively. Seven substrates, different in electronic and steric properties, were screened applying both reduction methods. For AH the best results in terms of enantioselectivity (e.e. up to 64%) were obtained by using [Ir(COD)(TetraMe-BITIOP)]Cl in the presence of DCDMH as additive. ATH was carried out with [IrCp*(CAMPY)Cl]Cl as catalyst, allowing the obtainment of the products with appreciable e.e. (up to 76%)

Efficient methodology to produce a duloxetine precursor using whole cells of Rhodotorula rubra

Different types of yeasts were employed as biocatalysts in the reduction of \u3b2-ketonitriles. The red microorganism, Rhodotorula rubra, was selected as the best performing catalyst in the reduction of different substituted ketonitriles giving total stereoselectivity in most cases (90-99% ee). In particular, its use as fresh and lyophilised cells was expanded to a semi-preparative scale for the production of the duloxetine precursor 1a. R. rubra was screened in the reduction of alkylation products in comparison with Pichia henricii for assignment of configuration of products 2a and 11a after derivatisation with S-MPA

Vancomycin-Iridium (III) Interaction: An Unexplored Route for Enantioselective Imine Reduction

The chiral structure of antibiotic vancomycin (Van) was exploited as an innovative coordination sphere for the preparation of an IrCp* based hybrid catalysts. We found that Van is able to coordinate iridium (Ir(III)) and the complexation was demonstrated by several analytical techniques such as MALDI-TOF, UV, Circular dichroism (CD), Raman IR, and NMR. The hybrid system so obtained was employed in the Asymmetric Transfer Hydrogenation (ATH) of cyclic imines allowing to obtain a valuable 61% e.e. (R) in the asymmetric reduction of quinaldine 2. The catalytic system exhibited a saturation kinetics with a calculated eciency of Kcat/KM = 0.688 h1mM

Isomeric carbazolocarbazoles: synthesis, characterization and comparative study in Organic Field Effect Transistors

We report here the synthesis and characterization of a new family of isomeric carbazolocarbazole derivatives, namely carbazolo[1,2-a]carbazole, carbazolo[3,2-b]carbazoleand carbazolo[4,3-c]carbazole. Thermal, optical, electrochemical, morphological and semiconducting properties have been studied to understand the influence of geometrical isomerism on the optoelectronic properties of these compounds. Different packing patterns have been observed by single crystal X-ray diffraction (XRD) which then correlate with the different morphologies of the evaporated thin films studied by XRD and Atomic Force Microscopy (AFM). The effect of N-substituents has also been evaluated for one of the isomers revealing a noticeable influence on the performance as organic semiconductors in Organic Field Effect Transistors (OFETs). A good p-channel field effect has been determined for N,N′-dioctylcarbazolo[4,3-c]carbazole with a mobility of 0.02 cm2 V−1 s−1 and Ion/Ioff ratio of 106 in air. These preliminary results demonstrate the promising properties of molecular carbazolocarbazole systems which should be further explored in the area of organic semiconducting materials

Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition.

A phase I/II trial was undertaken to determine maximum tolerated dose (MTD), toxicity, clinical efficacy and biological activity of bortezomib in patients with advanced stage primary or post-polycythemia vera/post-essential thrombocythemia myelofibrosis (MF). Bortezomib (0.8, 1.0, or 1.3 mg/m(2)) was administered on days 1, 4, 8, and 11 by intravenous push to patients previously resistant to at least one line of therapy, or with an intermediate/high risk IWG’s score [1]. Therapy was repeated every 28 days for 6 cycles. At 1.3 mg/m(2) dose, one of six patients experienced a dose limiting toxicity, and this was determined to be the MTD. Neither remissions or clinical improvements were recorded in 16 patients treated at this dose level, fulfilling the early stopping rule in the Simon two-stage study design. Major toxicity was on thrombocytopenia. In 9 out of 15 patients bortezomib proved able to reduce bone marrow vessel density. However, the agent was associated with worsening of markers of disease activity, like enhancement of hematopoietic CD34-positive progenitor cell mobilization, WT-1 gene expression in mononuclear cells, and down-regulation of CXCR4 expression on CD34-positive cells. Occurrence of both beneficial and detrimental biological effects claims further investigation on the mechanisms of the drug in MF

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era. Selecting cases, matching clinical benefit. A position paper from the Italian Group of Haematopathology (G.I.E.)

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

5.3 Left Ventricular Mass Independently Contributes to Long-Term Risk of Cardiovascular Morbidity and Mortality in a General Population: Data From the PAMELA Study

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An air-stable DPP-thieno-TTF copolymer for single-material solar cell devices and field effect transistors

Following an approach developed in our group to incorporate tetrathiafulvalene (TTF) units into conjugated polymeric systems, we have studied a low band gap polymer incorporating TTF as a donor component. This polymer is based on a fused thieno-TTF unit that enables the direct incorporation of the TTF unit into the polymer, and a second comonomer based on the diketopyrrolopyrrole (DPP) molecule. These units represent a donor–acceptor copolymer system, p(DPP-TTF), showing strong absorption in the UV–visible region of the spectrum. An optimized p(DPP-TTF) polymer organic field effect transistor and a single material organic solar cell device showed excellent performance with a hole mobility of up to 5.3 × 10–2 cm2/(V s) and a power conversion efficiency (PCE) of 0.3%, respectively. Bulk heterojunction organic photovoltaic devices of p(DPP-TTF) blended with phenyl-C71-butyric acid methyl ester (PC71BM) exhibited a PCE of 1.8%