One-pot multi-enzymatic synthesis of the four stereoisomers of 4-methylheptan-3-ol

The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible stereoisomers of this compd. were prepd. from 4-methylhept-4-en-3-one by a one-pot procedure in which the two stereogenic centers were created during two sequential redns. catalyzed by an ene-reductase (ER) and an alc. dehydrogenase (ADH), resp

Tryptophan Metabolism as Source of New Prognostic Biomarkers for FAP Patients

Familial adenomatous polyposis (FAP), a common inherited form of colorectal cancer (CRC), causes the development of hundreds to thousands of colonic adenomas in the colorectum beginning in early adolescence. In absence of a prophylactic surgery, FAP patients almost inevitably develop CRC by the age of 40 to 50. The lack of valuable prognostic biomarkers for FAP patients makes it difficult to predict when the progression from adenoma to malignant carcinoma occurs. Decreased tryptophan (TRP) plasma levels and increased indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan hydroxylase 1 (TPH1) enzymatic activities have been associated to tumour progression in CRC. In the present study, we aimed at investigating whether an altered TRP metabolism might also exist in FAP patients. Our results highlighted that plasma levels of TRP and its main catabolites are comparable between FAP patients and healthy subject. On the contrary, FAP patients presented significantly higher TRP levels with respect to high-grade adenoma (ADE) subjects and CRC patients. Obtained data lead us to evaluate IDO1 and TPH1 enzymes activity in the study groups. For both enzymes, it was possible to discriminate correctly between FAP subject and ADE/CRC patients with high sensitivities and specificities. By receiver operating characteristic (ROC) curve analysis, the cut-off values of IDO1 and TPH1 enzymatic activities associated to the presence of an active malignant transformation have been calculated as >38 and >5.5, respectively. When these cut-off values are employed, the area under the curve (AUC) is > 0.8 for both, indicating that TRP metabolism in patients with FAP may be used to monitor and predict the tumorigenic evolution

Novel Calibration systems for the dynamic and steady-state testing of digital instrument transformers

Within the frame of the European project 'Future Grid II-Metrology for the next-generation digital substation instrumentation', several partners developed traceable calibration systems which allow the calibration of conventional or non-conventional instrument transformers (IT) even with a sampled value (digital) output according to IEC 61869-9. Different setups are prepared to allow the calibration with complex test waveforms to emulate steady state, dynamic or temporary events during the assessment of the ITs. The laboratory calibration setups for either current transformers or voltage transformers are briefly described. Several results obtained for different kind of voltage or current transformers are presented

Structure/activity virtual screening and in vitro testing of small molecule inhibitors of 8-hydroxy-5-deazaflavin:NADPH oxidoreductase from gut methanogenic bacteria

Virtual screening techniques and in vitro binding/inhibitory assays were used to search within a set of more than 8,000 naturally occurring small ligands for candidate inhibitors of 8-hydroxy-5-deazaflavin:NADPH oxidoreductase (FNO) from Methanobrevibacter smithii, the enzyme that catalyses the bidirectional electron transfer between NADP+ and F420H2 during the intestinal production of CH4 from CO2. In silico screening using molecular docking classified the ligand-enzyme complexes in the range between − 4.9 and − 10.5 kcal/mol. Molecular flexibility, the number of H-bond acceptors and donors, the extent of hydrophobic interactions, and the exposure to the solvent were the major discriminants in determining the affinity of the ligands for FNO. In vitro studies on a group of these ligands selected from the most populated/representative clusters provided quantitative kinetic, equilibrium, and structural information on ligands’ behaviour, in optimal agreement with the predictive computational results

Pantograph-To-OHL Arc: Conducted Effects in DC Railway Supply System

The electrical arc occurring in the sliding contact between the supply contact line and the current collector (pantograph) of an electrical locomotive is a fast transient phenomenon able to degrade progressively the line-To-pantograph contact quality and, consequently, the continuity of operation. In order to increase the energy efficiency of the railway system, an inexpensive solution is constituted by the detection of the arc event by the analysis of voltage and current measurements already available on-board train. An essential activity to reach this objective is to set up a reliable electrical model of the railway system in which the arc events originate. To this end, this paper presents a combination of experimental and simulation analysis for the development of an electrical model of a direct current (dc) 3 kV railway system, which is aimed at better understanding the propagation of conducted effects generated by arc events. First, a laboratory experimental activity is carried out to investigate the electrical dynamic characteristics of the arc in a controlled environment. Then, a model of the dc railway system is derived and validated by using the experimental data collected in a measurement campaign on-board train. Finally, a sensitivity analysis of the main model parameters is carried out

The immunoreceptor tyrosine-based activation motif (ITAM)-related factors are increased in synovial tissue and vasculature of rheumatoid arthritic joints

Extent: 13p.Introduction: The immunoreceptor tyrosine-based activation motif (ITAM) pathway provides osteoclast co-stimulatory signals and regulates proliferation, survival and differentiation of effector immune cells. In the osteoclast, the receptors Triggering Receptor Expressed on Myeloid cells 2 (TREM2) and Osteoclast Associated Receptor (OSCAR) and their respective adaptor proteins, DAP12 and FcRγ mediate ITAM signals and induce calcium signaling and the crucial transcription factor, NFATc1. In rheumatoid arthritis (RA), OSCAR expression by monocytes is inversely correlated with disease activity. Additionally, serum levels of OSCAR are reduced in RA patients versus healthy controls suggesting that expression and secretion or cleavage of soluble (s) OSCAR is immune modulated. Recent data suggest that endothelial cells may also be a source of OSCAR. Methods: ITAM receptors, their adaptor proteins, and NFATc1 and cathepsin K were detected in human synovial tissues by immunohistochemistry. Synovial tissues from patients with active RA were compared with tissue from patients in remission, osteoarthritis (OA) patients and healthy individuals. OSCAR was measured by immunoassay in synovial fluids recovered from active RA and OA patients. Endothelial cells were cultured with or without 5 ng/mL TNF-α or IL-1β over 72 hours. Temporal expression of OSCAR mRNA was assessed by qRT PCR and OSCAR protein in the supernatant was measured by ELISA. Results: Significantly higher (P < 0.05) NFATc1-positive inflammatory cell aggregates were found in active RA tissues than in healthy synovial tissue. Similarly, the percentage of OSCAR, FcRγ, DAP12 and TREM2 positive cells was significantly higher in active RA tissues compared to the healthy synovial tissue. Notably, OSCAR was strongly expressed in the microvasculature of the active RA tissues (9/9), inactive RA (8/9) weakly in OA (4/9) but only in the lumen of healthy synovial tissue (0/8). OSCAR levels were detected in synovial fluids from both RA (47 to 152 ng/mL) and OA (112 to 145 ng/mL) patients. Moreover, OSCAR mRNA expression and soluble OSCAR release was stimulated by TNF-α and IL1-β in cultured endothelial cells. Conclusions: Increased levels of ITAM related factors were present in synovial tissue from active RA joints compared to OA and healthy joints. OSCAR was strongly expressed by the vasculature of active RA patients and membrane bound and soluble OSCAR was stimulated by inflammatory mediators in endothelial cells in vitro.Tania N Crotti, Anak ASSK Dharmapatni, Ekram Alias, Andrew CW Zannettino, Malcolm D Smith and David R Hayne

Cannabidiol in the acute phase of febrile infection-related epilepsy syndrome (FIRES)

Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure-free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES

SOT-MRAM 300mm integration for low power and ultrafast embedded memories

We demonstrate for the first time full-scale integration of top-pinned perpendicular MTJ on 300 mm wafer using CMOS-compatible processes for spin-orbit torque (SOT)-MRAM architectures. We show that 62 nm devices with a W-based SOT underlayer have very large endurance (> 5x10^10), sub-ns switching time of 210 ps, and operate with power as low as 300 pJ.Comment: presented at VLSI2018 session C8-

Asaia, a versatile acetic acid bacterial symbiont, capable of cross-colonizing insects of phylogenetically-distant genera and orders

Bacterial symbionts of insects have been proposed for blocking transmission of vector-borne pathogens. However, in many vector models the ecology of symbionts and their capability of cross-colonizing different hosts, an important feature in the symbiotic control approach, is poorly known. Here we show that the acetic acid bacterium Asaia, previously found in the malaria mosquito vector Anopheles stephensi, is also present in and capable of cross-colonizing other sugar-feeding insects of phylogenetically distant genera and orders. PCR, real-time PCR and in situ-hybridization experiments showed Asaia in the body of the mosquito Aedes aegypti and the leafhopper Scaphoideus titanus, vectors of human viruses and a grapevine phytoplasma, respectively. Cross colonization patterns of the body of Ae. aegypti, An. stephensi and S. titanus have been documented with Asaia strains isolated from An. stephensi or Ae. aegypti, and labelled with plasmid- or chromosome-encoded fluorescent proteins (Gfp and DsRed, respectively). Fluorescence and confocal microscopy showed that Asaia, administered with the sugar meal, efficiently colonized guts, male and female reproductive systems and the salivary glands. The ability in cross-colonizing insects of phylogenetically distant orders indicates that Asaia adopts body invasion mechanisms independent from the host biological characteristics. This versatility is an important property for the development of symbiont-based therapies of different vector-borne diseases

Deep ice as a geochemical reactor: Insights from iron speciation and mineralogy of dust in the Talos Dome ice core (East Antarctica)

Thanks to its insolubility, mineral dust is considered a stable proxy in polar ice cores. With this study we show that the Talos Dome ice core (TALDICE, Ross Sea sector of East Antarctica) displays evident and progressive signs of post-depositional processes affecting the mineral dust record below 1000g m deep. We apply a suite of established and cutting-edge techniques to investigate the properties of dust in TALDICE, ranging from concentration and grain size to elemental composition and Fe mineralogy. Results show that through acidic/oxidative weathering, the conditions of deep ice at Talos Dome promote the dissolution of specific minerals and the englacial formation of others, affecting primitive dust features. The expulsion of acidic atmospheric species from ice grains and their concentration in localized environments is likely the main process responsible for englacial reactions. Deep ice can be seen as a "geochemical reactor"capable of fostering complex reactions which involve both soluble and insoluble impurities. Fe-bearing minerals can efficiently help in exploring such transformations