Phosphonated Carbocyclic 2'-Oxa-3'-azanucleosides as New Antiretroviral Agents

Phosphonated carbocyclic 2¢-oxa-3¢-azanucleosides have been synthesized and tested for their antiretroviral activity. The obtained results have shown that some of the compounds were as powerful as azydothymidine in inhibiting the reverse transcriptase activity of the human retrovirus T-cell leukemia/lymphotropic virus type 1 and in protecting human peripheral blood mononuclear cells against human retrovirus T-cell leukemia/ lymphotropic virus type 1 transmission in vitro. These data indicate that phosphonated carbocyclic 2¢-oxa- 3¢-azanucleosides possess the necessary requirements to efficiently counteract infections caused by human retroviruses

Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML

Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues containing a carboxamide at the 4-position of the aryl ring and novel carbamates. These compounds were potent submicromolar LSD1 inhibitors in enzyme assays and were anti-proliferative against a panel of AML cell lines. LSD1 target engagement in cells was demonstrated through the effects on H3K4me2 protein expression, CD86, CD11b and CD14 levels

The use of antimicrobials in italian heavy pig fattening farms

Data on antimicrobial use (AMU) in heavy pig production (>150 kg) are limited. The aim of this study was to investigate the AMU in this production. Data from 2015 were collected for 143 fattening farms. The AMU was estimated through a treatment index per 100 days (TI100) using the defined daily dose animal for Italy (DDDAit). When possible, a comparison with the European Medicines Agency’s defined daily doses for animals (DDDvet) was performed. The median TI100 was 10.7 (range, 0.2–49.5). Group treatments represented 94.6% of overall consumption. The AMU calculated using DDDAit and DDDvet were strongly correlated (ρ = 0.976; p < 0.001). The AMU was negatively correlated with injectables use (ρ = −0.46, p < 0.001) and positively correlated with oral products (ρ = 0.21, p = 0.014), premixes (ρ = 0.26, p = 0.002), and mortality (ρ = 0.18; p = 0.027). Farm size was negatively correlated with AMU (ρ = −0.29, p < 0.001). Smaller farms were more frequently above the median TI100 (odds ratio = 2.3, 95% confidence interval = 1.2–4.7), suggesting that they may have lower biosecurity and management standards. The results of this study should provide useful insights for the development of an Italian monitoring system

Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase.

The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged α-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1

Charge collection and capacitance–voltage analysis in irradiated n-type magnetic Czochralski silicon detectors

Abstract The depletion depth of irradiated n-type silicon microstrip detectors can be inferred from both the reciprocal capacitance and from the amount of collected charge. Capacitance voltage ( C – V ) measurements at different frequencies and temperatures are being compared with the bias voltage dependence of the charge collection on an irradiated n-type magnetic Czochralski silicon detector. Good agreement between the reciprocal capacitance and the median collected charge is found when the frequency of the C – V measurement is selected such that it scales with the temperature dependence of the leakage current. Measuring C – V characteristics at prescribed combinations of temperature and frequency allows then a realistic estimate of the depletion characteristics of irradiated silicon strip detectors based on C – V data alone

The Data Quality Monitoring for the CMS Silicon Strip Tracker

The CMS Silicon Strip Tracker (SST), consisting of more than 10 million channels, is organized in about 15,000 detector modules and it is the largest silicon strip tracker ever built for high energy physics experiments. The Data Quality Monitoring system for the Tracker has been developed within the CMS Software framework. More than 100,000 monitorable quantities need to be managed by the DQM system that organizes them in a hierarchical structure reflecting the detector arrangement in subcomponents and the various levels of data processing. Monitorable quantities computed at the level of individual detectors are processed to extract automatic quality checks and summary results that can be visualized with specialized graphical user interfaces. In view of the great complexity of the CMS Tracker detector the standard visualization tools based on histograms have been complemented with 2 and 3 dimensional graphical images of the subdetector that can show the whole detector down to single channel resolution. The functionalities of the CMS Silicon Strip Tracker DQM system and the experience acquired during the SST commissioning will be described

Advancing the scientific study of prehospital mass casualty response through a Translational Science process: the T1 scoping literature review stage

PurposeThe European Union Horizon 2020 research and innovation funding program awarded the NIGHTINGALE grant to develop a toolkit to support first responders engaged in prehospital (PH) mass casualty incident (MCI) response. To reach the projects' objectives, the NIGHTINGALE consortium used a Translational Science (TS) process. The present work is the first TS stage (T1) aimed to extract data relevant for the subsequent modified Delphi study (T2) statements.MethodsThe authors were divided into three work groups (WGs) MCI Triage, PH Life Support and Damage Control (PHLSDC), and PH Processes (PHP). Each WG conducted simultaneous literature searches following the PRISMA extension for scoping reviews. Relevant data were extracted from the included articles and indexed using pre-identified PH MCI response themes and subthemes.ResultsThe initial search yielded 925 total references to be considered for title and abstract review (MCI Triage 311, PHLSDC 329, PHP 285), then 483 articles for full reference review (MCI Triage 111, PHLSDC 216, PHP 156), and finally 152 articles for the database extraction process (MCI Triage 27, PHLSDC 37, PHP 88). Most frequent subthemes and novel concepts have been identified as a basis for the elaboration of draft statements for the T2 modified Delphi study.ConclusionThe three simultaneous scoping reviews allowed the extraction of relevant PH MCI subthemes and novel concepts that will enable the NIGHTINGALE consortium to create scientifically anchored statements in the T2 modified Delphi study

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin