Synthesis of stabilized analogues of fragments of Neisseria meningitidis type A capsular polysaccharide

The resistance to Neisseria meningitidis (N. m.), a gram-negative bacterium causing meningitis, is mediated by the presence of antibodies directed against its capsular polysaccharides (CPS), which are associated with different serogroups. One of the most virulent is serotype A (Men A), whose CPS is constituted of (\uf0ae6)-N-acetylmannosamine \uf061-1-O-Phosphate as a repeating unit. The already existing vaccines against N.m. give a T-cell independent immune response, therefore inefficient in infants. The response can be improved by conjugation of the saccharidic portion to a protein carrier, which invokes T-cell involvement. In addition, anomeric phosphodiester bridges are chemically labile and therefore not appropriate for a vaccine. To overcome these problems, phosphonate 4 and its oligomers 5 and 7 have been synthesised as stable analogues of the repeating unit of Men A CPS. Key steps of the synthetic strategy are: a) Synthesis of building blocks 3 and 4, the latter bearing a spacer at the reducing end suitable for conjugation to a proper protein carrier; b) Coupling of 3 with 4 via Mitsunobu reaction providing 5, followed by 6'-O-deacetylation and a second Mitsunobu coupling to give trimer 7. After removal of the protecting groups, the synthesized compounds have been evaluated through a competitive ELISA assay (IC50 values) by use of Men A antiserum. Moreover, preliminary approaches towards the carba-analogue 8 of N-acetylmannosamine 1-O-phosphate, a key building block for the synthesis of a new type of Men A analogues, will be also discussed

The course of the cystic artery during laparoscopic cholecystectomy

Proper recognition of the particular structures that form the triangle of Calot is essential for the proper and safe performance of laparoscopic cholecystectomy. Proper recognition, ligation, and cut of the cystic duct and cystic artery with branches (dorsal and ventral) remain an integral condition for the removal of the gallbladder. Calot’s triangle, as an orientation structure, determines the most common location of the cystic artery. The triangle of Calot is one of the most variable regions of the abdomen in terms of anatomy. The aim of this study was to evaluate how important for surgery is the detailed anatomical recognition of the main branches of the cystic artery in Calot’s triangle during laparoscopic cholecystectomy. Relations of the main branches of the cystic artery were evaluated in 88 patients that underwent laparoscopic cholecystectomy at the Department of General Surgery of the District Specialistic Hospital of Lublin. The anatomical relations of cystic duct and artery were classified into typical and variant types. Significantly more frequently variants of cystic artery were observed in women. However, the time of the procedure was not significantly related with the type of cystic artery

The Low Redshift survey at Calar Alto (LoRCA)

The Baryon Acoustic Oscillation (BAO) feature in the power spectrum of galaxies provides a standard ruler to measure the accelerated expansion of the Universe. To extract all available information about dark energy, it is necessary to measure a standard ruler in the local, z<0.2, universe where dark energy dominates most the energy density of the Universe. Though the volume available in the local universe is limited, it is just big enough to measure accurately the long 100 Mpc/h wave-mode of the BAO. Using cosmological N-body simulations and approximate methods based on Lagrangian perturbation theory, we construct a suite of a thousand light-cones to evaluate the precision at which one can measure the BAO standard ruler in the local universe. We find that using the most massive galaxies on the full sky (34,000 sq. deg.), i.e. a K(2MASS)<14 magnitude-limited sample, one can measure the BAO scale up to a precision of 4\% and 1.2\% using reconstruction). We also find that such a survey would help to detect the dynamics of dark energy.Therefore, we propose a 3-year long observational project, named the Low Redshift survey at Calar Alto (LoRCA), to observe spectroscopically about 200,000 galaxies in the northern sky to contribute to the construction of aforementioned galaxy sample. The suite of light-cones is made available to the public.Comment: 15 pages. Accepted in MNRAS. Please visit our website: http://lorca-survey.ft.uam.es

The Low Redshift survey at Calar Alto (LoRCA)

The Baryon Acoustic Oscillation (BAO) feature in the power spectrum of galaxies provides a standard ruler to measure the accelerated expansion of the Universe. To extract all available information about dark energy, it is necessary to measure a standard ruler in the local, z<0.2, universe where dark energy dominates most the energy density of the Universe. Though the volume available in the local universe is limited, it is just big enough to measure accurately the long 100 Mpc/h wave-mode of the BAO. Using cosmological N-body simulations and approximate methods based on Lagrangian perturbation theory, we construct a suite of a thousand light-cones to evaluate the precision at which one can measure the BAO standard ruler in the local universe. We find that using the most massive galaxies on the full sky (34,000 sq. deg.), i.e. a K(2MASS)<14 magnitude-limited sample, one can measure the BAO scale up to a precision of 4\% and 1.2\% using reconstruction). We also find that such a survey would help to detect the dynamics of dark energy.Therefore, we propose a 3-year long observational project, named the Low Redshift survey at Calar Alto (LoRCA), to observe spectroscopically about 200,000 galaxies in the northern sky to contribute to the construction of aforementioned galaxy sample. The suite of light-cones is made available to the public.Comment: 15 pages. Accepted in MNRAS. Please visit our website: http://lorca-survey.ft.uam.es

Spectroscopic classification of X-ray sources in the Galactic Bulge Survey

We present the classification of 26 optical counterparts to X-ray sources discovered in the Galactic Bulge Survey. We use (time-resolved) photometric and spectroscopic observations to classify the X-ray sources based on their multi-wavelength properties. We find a variety of source classes, spanning different phases of stellar/binary evolution. We classify CX21 as a quiescent cataclysmic variable (CV) below the period gap, and CX118 as a high accretion rate (nova-like) CV. CXB12 displays excess UV emission, and could contain a compact object with a giant star companion, making it a candidate symbiotic binary or quiescent low mass X-ray binary (although other scenarios cannot be ruled out). CXB34 is a magnetic CV (polar) that shows photometric evidence for a change in accretion state. The magnetic classification is based on the detection of X-ray pulsations with a period of 81 $\pm$ 2 min. CXB42 is identified as a young stellar object, namely a weak-lined T Tauri star exhibiting (to date unexplained) UX Ori-like photometric variability. The optical spectrum of CXB43 contains two (resolved) unidentified double-peaked emission lines. No known scenario, such as an AGN or symbiotic binary, can easily explain its characteristics. We additionally classify 20 objects as likely active stars based on optical spectroscopy, their X-ray to optical flux ratios and photometric variability. In 4 cases we identify the sources as binary stars.Comment: Accepted for publication in MNRA

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: Angular clustering tomography and its cosmological implications

We investigate the cosmological implications of studying galaxy clustering using a tomographic approach applied to the final BOSS DR12 galaxy sample, including both auto- and cross-correlation functions between redshift shells. We model the signal of the full shape of the angular correlation function, $\omega(\theta)$, in redshift bins using state-of-the-art modelling of non-linearities, bias and redshift-space distortions. We present results on the redshift evolution of the linear bias of BOSS galaxies, which cannot be obtained with traditional methods for galaxy-clustering analysis. We also obtain constraints on cosmological parameters, combining this tomographic analysis with measurements of the cosmic microwave background (CMB) and type Ia supernova (SNIa). We explore a number of cosmological models, including the standard $\Lambda$CDM model and its most interesting extensions, such as deviations from w_\rm{DE} = -1, non-minimal neutrino masses, spatial curvature and deviations from general relativity using the growth-index $\gamma$ parametrisation. These results are, in general, comparable to the most precise present-day constraints on cosmological parameters, and show very good agreement with the standard model. In particular, combining CMB, $\omega(\theta)$ and SNIa, we find a value of w_\rm{DE} consistent with $-1$ to a precision better than 5\% when it is assumed to be constant in time, and better than 6\% when we also allow for a spatially-curved Universe.Comment: 21 pages, 18 figures, accepted for publication MNRAS. The data used in this analysis is publicly available at https://sdss3.org/science/boss_publications.ph