Synthetic Studies on the Pseudopterosins and trans-4-Methyl-L-Proline

The Pseudopterosin family of diterpene glycosides was isolated in 1986 from the Caribbean sea-plume Pseudopterogorgia elisabethea. Pseudopterosin E is one of the most potent anti-inflammatory agents currently know, being fifty times more active than indomethacin in preventing phorbol myristate acetate topically-induced inflammation in the mouse ear oedema model. In the first section of this thesis, an attempted synthetic strategy towards Pseudopterosin E is reported. Our initial retrosynthesis adopted an intramolecular Diels- Alder reaction (IMDA) to form the tricarbocyclic core of the natural product. It was envisaged that elaboration of the IMDA product would lead to a key intermediate in the Corey et al. synthesis of Pseudopterosin E. The remainder of our synthesis would be after Corey. Free trans-4-methyl-L-proline was first obtained from Worcester Pearmain apples in 1952. It is a constituent part of several natural products; Grisemelycin, Mycoplanecin A, and the Monamycins, all of which have potent biological activity profiles. In the second section of this thesis, several synthetic approaches to trans-4- methyl-L-proline are reported

Nonsteroidal antiâ inflammatory drugs (NSAIDs) and paracetamol do not affect 6â month moodâ stabilizing treatment outcome among 482 patients with bipolar disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136478/1/da22601_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136478/2/da22601.pd

Chronic lung allograft dysfunction: Definition, diagnostic criteria, and approaches to treatment―A consensus report from the Pulmonary Council of the ISHLT

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Patterns of changes in bipolar depressive symptoms revealed by trajectory analysis among 482 patients with bipolar disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149731/1/bdi12715_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149731/2/bdi12715.pd

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Exile Vol. XXIII No. 2

PROSE The End of East by Libby Thomas 3-12 Lilt by Andrew Calabrese 13 The Egg Lady by Nancy Jones 14-20 The International Man by Chip Finefrock 21-31 MUSIC Theme and Variations Op.2, No 1. by J. J. Fuerst 32-38 POETRY Thrown Out Of The Game by Herberto Padilla to Yannis Ritzos in a Greek jail (Translated from the Spanish by José de Armas) 39 Plumb-Creek In Late Sunlight by Lenore Mayhew 40 untitled by Sharon Singleton 41 untitled by Sharon Singleton 42 A Dance Of Stones by Lawrence Weber 43-44 Carp and Crane by William McNaughton 45 Mountain Ash by Dawn Patnode 46-49 untitled by Mary de Rachewiltz 50 Kai Gar Onar Ek Dios Estin by William McNaughton 51 acute angles by Gay Parks 52 Annihilating All Made To A Thought by Tony Stoneburner 53 Dead Fish by Deneise Deter 54 Changing by Deb Allbery 54 Finish Lines by David A. Goldblatt 55 Malinche\u27s Sister by Tona Dickerson 56 Tarde en el hospital by Carlos Peoza Veliz 57 Afternoon in the Hospital by Carlos Peoza Veliz (Tanslated from the Spanish by Joan Straub) 57 Cuadrados Y Angulos by Alfonaina Storni 58 Squares and Angles by Alfonaina Storni (Translated from the Spanish by Joan Straub) 58 INK DRAWINGS untitled by Susan Hoagman 2 Self-Portrait or Darla by Julia Weatherford 59 untitled by Katy Booth 70 ESSAYS On As For Poets by Gary Snyder 60-61 Joseph Heller\u27s Something Happened and the Problem of Community in Modern America by Jack Kirby 62-68 EDITOR\u27S NOTE by Lawrence Weber 69-70 CONTRIBUTORS 71-72 The cover ink drawing by Cathy Ries is entitled, Exercise In Exaggerated Contours

The Democratic Biopolitics of PrEP

PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs

MicroRNAs (miRNAs) are 19–22-nucleotide noncoding RNAs that post-transcriptionally regulate mRNA targets. We have identified endogenous miRNA binding sites in mouse embryonic stem cells (mESCs), by performing photo-cross-linking immunoprecipitation using antibodies to Argonaute (Ago2) followed by deep sequencing of RNAs (CLIP-seq). We also performed CLIP-seq in Dicer[superscript −/−] mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA dependent. A significantly enriched motif, GCACUU, was identified only in wild-type mESCs in 3′ untranslated and coding regions. This motif matches the seed of a miRNA family that constitutes ~68% of the mESC miRNA population. Unexpectedly, a G-rich motif was enriched in sequences cross-linked to Ago2 in both the presence and absence of miRNAs. Expression analysis and reporter assays confirmed that the seed-related motif confers miRNA-directed regulation on host mRNAs and that the G-rich motif can modulate this regulation.Leukemia & Lymphoma Society of AmericaUnited States. Public Health Service (Grant R01-GM34277)United States. Public Health Service (Grant R01-CA133404)National Cancer Institute (U.S.) (Grant P01-CA42063)National Cancer Institute (U.S.) Cancer Center Support (Grant P30-CA14051

Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

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