A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Preparation of beta-amino or alpha ,beta-diamino esters derived from serine

The invention relates to the prepn. of esters R1R2NCH2CH(Nu)CO2R3 (R1-R3 are protecting groups and Nu is a nucleophilic group) by reaction of R1R2NCH(CH2-Y)CO2R3 (Y is a leaving group) with a nucleophile. Thus, treatment of (R)-Bn2NCH(CH2O3SMe)CO2Me with NaN3 in MeCN afforded 90% (S)-Bn2NCH2CH(N3)CO2Me. [on SciFinder (R)

Synthetic studies towards (-)-lemonomycin, synthesis of fused tetracycles

The asym. synthesis of 1,3-lactol-bridged tetrahydroisoquinolines I [R = SiMe2CMe3, CH2Ph; R1 = CH2CH(CO2Me)2; R2 = CO2CH2Ph] was developed. Subsequent cyclizations of I (R = SiMe2CMe3, CH2Ph) under acidic conditions lead to the formation of a tricyclic enamides II [R = SiMe2CMe3, CH2Ph; R1 = CH2CH(CO2Me)2; R2 = CO2CH2Ph]. II [R = CH2Ph, R1 = CH2CH(CO2Me)2, R2 = CO2CH2Ph] was in turn converted to a tetracyclic compd. III. [on SciFinder (R)

Asymmetric synthesis of protected γ-carboxy-L-glutamic acid

An asym. synthesis of an orthogonally protected gamma -carboxy-L-glutamic acid (L-Gla) is developed featuring a key proline-catalyzed Knoevenagel condensation between Garner's aldehyde and Meldrum's acid. [on SciFinder (R)

Retrotransfer or gene capture: a feature of conjugative plasmids, with ecological and evolutionary significance

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Aziridinium from N,N-dibenzyl serine methyl ester: Synthesis of enantiomerically pure beta -amino and alpha ,beta -diamino esters

Reaction of N,N-dibenzyl-O-methylsulfonyl serine Me ester with a variety of heteronucleophiles (sodium azide, sodium phthalimide, amines, thiols) and carbanions (sodium malonate) gave, via an aziridinium intermediate, the corresponding beta -amino or alpha ,beta -diamino ester in good to excellent yield. A short synthesis of orthogonally protected and enantiomerically pure 2,3-diamino propionate (Dap) is described. [on SciFinder (R)

Asymmetric Synthesis of 2,4,6-Trideoxy-4-(dimethylamino)-3-C-methyl-Llyxohexopyranose (Lemonose)

L-Lemonose, the glycosidic part of (–)-lemonomycin, has been synthesized in ten steps with 18% overall yield from Dthreonine. The key steps are a double, highly diastereoselective Grignard addition to a Weinreb amide and a chemoselective oxidation of a primary alcohol in the presence of a secondary alcohol, a tertiary alcohol and a tertiary amine, leading directly to the lactol

Inhibitors of the Neisseria meningitidis PilF ATPase provoke type IV pilus disassembly

International audienceDespite the availability of antibiotics and vaccines, Neisseria meningitidis remains a major cause of meningitis and sepsis in humans. Due to its extracellular lifestyle, bacterial adhesion to host cells constitutes an attractive therapeutic target. Here, we present a high-throughput microscopy-based approach that allowed the identification of compounds able to decrease type IV pilus-mediated interaction of bacteria with endothelial cells in the absence of bacterial or host cell toxicity. Compounds specifically inhibit the PilF ATPase enzymatic activity that powers type IV pilus extension but remain inefficient on the ATPase that promotes pilus retraction, thus leading to rapid pilus disappearance from the bacterial surface and loss of pili-mediated functions. Structure activity relationship of the most active compound identifies specific moieties required for the activity of this compound and highlights its specificity. This study therefore provides compounds targeting pilus biogenesis, thereby inhibiting bacterial adhesion, and paves the way for a novel therapeutic option for meningococcal infections

Effects of dietary arginine supplementation in pregnant mares on maternal metabolism, placental structure and function and foal growth

Foals born to primiparous mares are lighter and less mature than those born to multiparous dams. Factors driving this difference are not totally understood. Using 7 multiparous and 6 primiparous standardbred mares, we demonstrated that, in late gestation, primiparous mares were less insulin resistant compared to multiparous mares, and that their foals had reduced plasma amino-acid concentrations at birth compared to foals born to multiparous mares. Vascular development, as observed through structure and gene expression, and global DNA methylation were also reduced in primiparous placentas. Another group of 8 primiparous mares was orally supplemented with L-arginine (100 g/day, 210d to term). L-arginine improved pregnancy-induced insulin resistance and increased maternal L-arginine and L-ornithine plasma concentrations but foal plasma amino acid concentrations were not affected at birth. At birth, foal weight and placental biometry, structure, ultra-structure and DNA methylation were not modified. Placental expression of genes involved in glucose and fatty acid transfers was increased. In conclusion, maternal insulin resistance in response to pregnancy and placental function are reduced in primiparous pregnancies. Late-gestation L-arginine supplementation may help primiparous mares to metabolically adapt to pregnancy and improve placental function. More work is needed to confirm these effects and ascertain optimal treatment condition