Recyclable Organocatalysis of One-pot Michael/Mannich/Lactamization Sequence for Asymmetric Synthesis of Fluorinated Poly-substituted 2-Piperidinones

2-piperidinone (δ-lactam), a bio-interesting nitrogen-containing six-membered ring compound, has attracted much interest from researchers both in synthetic and medicinal chemistry. Polysubstituted piperidine derivatives, such as the δ-lactam, serve as a synthon for numerous biologically relevant structures and pharmaceutical agents. A novel one-pot asymmetric Michael/Mannich/Lactamization sequence promoted by recyclable fluorous bifunctional cinchona alkaloid–thiourea organocatalysts is introduced for the synthesis of polysubstituted 2-piperidinones bearing four contiguous stereocenters, one of which is a fluorinated quaternary chiral center with excellent stereoselectivities (ee up to \u3e99%, dr up to \u3e20:1)

Dynamic modelling of hepatitis C virus transmission among people who inject drugs: a methodological review

Equipment sharing among people who inject drugs (PWID) is a key risk factor in infection by hepatitis C virus (HCV). Both the effectiveness and cost-effectiveness of interventions aimed at reducing HCV transmission in this population (such as opioid substitution therapy, needle exchange programs or improved treatment) are difficult to evaluate using field surveys. Ethical issues and complicated access to the PWID population make it difficult to gather epidemiological data. In this context, mathematical modelling of HCV transmission is a useful alternative for comparing the cost and effectiveness of various interventions. Several models have been developed in the past few years. They are often based on strong hypotheses concerning the population structure. This review presents compartmental and individual-based models in order to underline their strengths and limits in the context of HCV infection among PWID. The final section discusses the main results of the papers

Impact of a treatment as prevention strategy on hepatitis C virus transmission and on morbidity in people who inject drugs

Background: Highly effective direct-acting antiviral (DAA) regimens (90% efficacy) are becoming available for hepatitis C virus (HCV) treatment. This therapeutic revolution leads us to consider possibility of eradicating the virus. However, for this, an effective cascade of care is required. Methods: In the context of the incoming DAAs, we used a dynamic individual-based model including a model of the people who inject drugs (PWID) social network to simulate the impact of improved testing, linkage to care, and adherence to treatment, and of modified treatment recommendation on the transmission and on the morbidity of HCV in PWID in France. Results: Under the current incidence and cascade of care, with treatment initiated at fibrosis stage $\ge$F2, the HCV prevalence decreased from 42.8% to 24.9% [95% confidence interval 24.8%--24.9%] after 10 years. Changing treatment initiation criteria to treat from F0 was the only intervention leading to a substantial additional decrease in the prevalence, which fell to 11.6% [11.6%--11.7%] at 10 years. Combining this change with improved testing, linkage to care, and adherence to treatment decreased HCV prevalence to 7% [7%--7.1%] at 10 years and avoided 15.3% [14.0%-16.6%] and 29.0% [27.9%--30.1%] of cirrhosis complications over 10 and 40 years respectively. Conclusion: A high decrease in viral transmission occurs only when treatment is initiated before liver disease progresses to severe stages, suggesting that systematic treatment in PWID, where incidence remains high, would be beneficial. However, eradication will be difficult to achieve

Near-Optimal Evasion of Convex-Inducing Classifiers

Classifiers are often used to detect miscreant activities. We study how an adversary can efficiently query a classifier to elicit information that allows the adversary to evade detection at near-minimal cost. We generalize results of Lowd and Meek (2005) to convex-inducing classifiers. We present algorithms that construct undetected instances of near-minimal cost using only polynomially many queries in the dimension of the space and without reverse engineering the decision boundary.Comment: 8 pages; to appear at AISTATS'201

Forming Early-type Galaxies in Groups Prior to Cluster Assembly

We study a unique proto-cluster of galaxies, the supergroup SG1120-1202. We quantify the degree to which morphological transformation of cluster galaxies occurs prior to cluster assembly in order to explain the observed early-type fractions in galaxy clusters at z=0. SG1120-1202 at z~0.37 is comprised of four gravitationally bound groups that are expected to coalesce into a single cluster by z=0. Using HST ACS observations, we compare the morphological fractions of the supergroup galaxies to those found in a range of environments. We find that the morphological fractions of early-type galaxies (~60 %) and the ratio of S0 to elliptical galaxies (0.5) in SG1120-1202 are very similar to clusters at comparable redshift, consistent with pre-processing in the group environment playing the dominant role in establishing the observed early-type fraction in galaxy clusters.Comment: 5 pages, 2 figures, 2 tables. Accepted for publication in ApJ Letter

The mass distribution in an assembling super galaxy group at z=0.37z=0.37

We present a weak gravitational lensing analysis of supergroup SG1120$-$1202, consisting of four distinct X-ray-luminous groups, that will merge to form a cluster comparable in mass to Coma at $z=0$. These groups lie within a projected separation of 1 to 4 Mpc and within $\Delta v=550$ km s$^{-1}$ and form a unique protocluster to study the matter distribution in a coalescing system. Using high-resolution {\em HST}/ACS imaging, combined with an extensive spectroscopic and imaging data set, we study the weak gravitational distortion of background galaxy images by the matter distribution in the supergroup. We compare the reconstructed projected density field with the distribution of galaxies and hot X-ray emitting gas in the system and derive halo parameters for the individual density peaks. We show that the projected mass distribution closely follows the locations of the X-ray peaks and associated brightest group galaxies. One of the groups that lies at slightly lower redshift ($z\approx 0.35$) than the other three groups ($z\approx 0.37$) is X-ray luminous, but is barely detected in the gravitational lensing signal. The other three groups show a significant detection (up to $5 \sigma$ in mass), with velocity dispersions between $355^{+55}_{-70}$ and $530^{+45}_{-55}$ km s$^{-1}$ and masses between $0.8^{+0.4}_{-0.3} \times 10^{14}$ and $1.6^{+0.5}_{-0.4}\times 10^{14} h^{-1} M_{\odot}$, consistent with independent measurements. These groups are associated with peaks in the galaxy and gas density in a relatively straightforward manner. Since the groups show no visible signs of interaction, this supports the picture that we are catching the groups before they merge into a cluster.Comment: 10 pages, 10 figures, accepted for publication by Astronomy & Astrophysic