Solid-Phase Organic Chemistry: Linkers and Functionalized Solid Supports

Since 1994, the quantity of papers published in the field of solid-phase organic chemistry has been growing almost exponentially. The scope of the existing peptide and oligonucleotide methodology has been greatly extended to accommodate those compound classes of interest to medicinal chemists. New polymer-bound linkers and functionalized resins have been developed to improve the versatility of the approach and to facilitate the preparation of molecules not accessible with existing technologies

Risikofaktoren für Übergewicht

Die vorliegende Arbeit untersucht eine aus dem Jahr 2001 vorliegende Stichprobenuntersuchung aus Bayern mittels verschiedener statistischer Modelle hinsichtlich der Signifikanz von 6 verschiedenen Risikofaktoren für Übergewicht, bzw. Adipositas bei Kindern. Die Risikofaktoren sind: BMI der Mutter, Gewichtszunahme im frühkindlichen Alter, intrauterine Nikotinexposition, Verzicht auf Stillen, Fernsehkonsum und sozioökonomischer Status der Eltern. Es wurde insbesondere die Frage untersucht, ob die Voraussetzung der Linerarität für eine lineare Regression bei den erfaßten Risikofaktoren vorliegt, oder diese bei einer Verschiebung nur der oberen Perzentilen der Häufigkeitsverteilung verletzt wird. Es konnte durch die Auswertung der Häufigkeitsverteilungen und eines rechnerisch ermittelten Referenzwertes nachgewiesen werden, daß man zumindest bei einigen der Risikofaktoren davon ausgehen muß, daß die Voraussetzung der Linearität verletzt wurde. Aus diesem Grund wurde für alle Risikofaktoren zusätzlich eine logistische Regression hinsichtlich drei verschiedener dichotomer Zielgrößen durchgeführt. Diese führten wie auch die lineare Regression zu der Schlußfolgerung, daß alle 6 Risikofaktoren signifikant sind. Dies läßt sich auch trotz fehlender Linearität bei einigen Risikofaktoren vor allem durch die Größe der Stichprobe begründen

Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance.

Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.Support was provided by the Wellcome Trust (A.C.H., J.L.H., G.R) and Cancer Research UK (A.C.H.), Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust (L.A.-D.; A.C.H.); Marie Curie and EMBO fellowships (M.S.).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150519/ncomms8090/full/ncomms8090.html

Knowledge integration in One Health policy formulation, implementation and evaluation

The One Health concept covers the interrelationship between human, animal and environmental health and requires multistakeholder collaboration across many cultural, disciplinary, institutional and sectoral boundaries. Yet, the implementation of the One Health approach appears hampered by shortcomings in the global framework for health governance. Knowledge integration approaches, at all stages of policy development, could help to address these shortcomings. The identification of key objectives, the resolving of trade-offs and the creation of a common vision and a common direction can be supported by multicriteria analyses. Evidence-based decision-making and transformation of observations into narratives detailing how situations emerge and might unfold in the future can be achieved by systems thinking. Finally, transdisciplinary approaches can be used both to improve the effectiveness of existing systems and to develop novel networks for collective action. To strengthen One Health governance, we propose that knowledge integration becomes a key feature of all stages in the development of related policies. We suggest several ways in which such integration could be promoted

flowLearn: Fast and precise identification and quality checking of cell populations in flow cytometry

Lux M, Brinkman RR, Chauve C, et al. flowLearn: Fast and precise identification and quality checking of cell populations in flow cytometry. Bioinformatics. 2018;34(13):2245-2253.Motivation Identification of cell populations in flow cytometry is a critical part of the analysis and lays the groundwork for many applications and research discovery. The current paradigm of manual analysis is time consuming and subjective. A common goal of users is to replace manual analysis with automated methods that replicate their results. Supervised tools provide the best performance in such a use case, however they require fine parameterization to obtain the best results. Hence, there is a strong need for methods that are fast to setup, accurate and interpretable. Results flowLearn is a semi-supervised approach for the quality-checked identification of cell populations. Using a very small number of manually gated samples, through density alignments it is able to predict gates on other samples with high accuracy and speed. On two state-of-the-art data sets, our tool achieves median(F1)-measures exceeding 0.99 for 31%, and 0.90 for 80% of all analyzed populations. Furthermore, users can directly interpret and adjust automated gates on new sample files to iteratively improve the initial training

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log(10) increase (i.e., a similar to 3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination. with increased transmissibility and an unfamiliar molecular mechanism of virulence

PS-COD and PS-9-BBN: polymer-supported reagents for solution-phase parallel synthesist

1,5-Cyclooctadiene was deprotonated under LICKOR conditions and reacted with Merrifield resin to afford an immobilized cyclooctadiene in high yield. This polymer is effective as a halogen scavenger, while hydroboration leads to a supported 9-BBN analogue. The latter exhibits similar regioselectivity to 9-BBN in olefin hydroboration