136 research outputs found
Kinetic Resolution in Asymmetric Epoxidation using Iminium Salt Catalysis
The first reported examples of kinetic resolution in epoxidation reactions using iminium salt catalysis are described, providing up to 99% ee in the epoxidation of racemic cis-chromenes
Formal synthesis of (+)-lactacystin from l-serine
A formal, stereocontrolled synthesis of lactacystin has been completed from t-Bu-O-l-serine, providing the key intermediate 13, also useful for the generation of a range of C-9 analogues
Feasibility of a mental practice intervention in stroke patients in nursing homes; a process evaluation
<p>Abstract</p> <p>Background</p> <p>Within a multi-centre randomised controlled trial in three nursing homes, a process evaluation of a mental practice intervention was conducted. The main aims were to determine if the intervention was performed according to the framework and to describe the therapists' and participants' experiences with and opinions on the intervention.</p> <p>Methods</p> <p>The six week mental practice intervention was given by physiotherapists and occupational therapists in the rehabilitation teams and consisted of four phases: explanation of imagery, teaching patients how to use imagery, using imagery as part of therapy, and facilitating the patient in using it alone and for new tasks. It had a mandatory and an optional part. Data were collected by means of registration forms, pre structured patient files, patient logs and self-administered questionnaires.</p> <p>Results</p> <p>A total of 14 therapists and 18 patients with stroke in the sub acute phase of recovery were involved. Response rates differed per assessment (range 57-93%). Two patients dropped out of the study (total n = 16). The mandatory part of the intervention was given to 11 of 16 patients: 13 received the prescribed amount of mental practice and 12 practiced unguided outside of therapy. The facilitating techniques of the optional part of the framework were partly used. Therapists were moderately positive about the use of imagery in this specific sample. Although it was more difficult for some patients to generate images than others, all patients were positive about the intervention and reported perceived short term benefits from mental practice.</p> <p>Conclusions</p> <p>The intervention was less feasible than we hoped. Implementing a complex therapy delivered by existing multi-professional teams to a vulnerable population with a complex pathology poses many challenges.</p
Genome of the Avirulent Human-Infective TrypanosomeâTrypanosoma rangeli
Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts. Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins. Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets
RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients
Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p
Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7Ă10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4Ă10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4Ă10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat
Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk
Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HRâ=â0.85, 95% CI 0.80-0.90, Pâ=â3.9Ă10â8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer
CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey - The Hubble Space Telescope Observations, Imaging Data Products and Mosaics
This paper describes the Hubble Space Telescope imaging data products and
data reduction procedures for the Cosmic Assembly Near-IR Deep Extragalactic
Legacy Survey (CANDELS). This survey is designed to document the evolution of
galaxies and black holes at , and to study Type Ia SNe beyond
. Five premier multi-wavelength sky regions are selected, each with
extensive multiwavelength observations. The primary CANDELS data consist of
imaging obtained in the Wide Field Camera 3 / infrared channel (WFC3/IR) and
UVIS channel, along with the Advanced Camera for Surveys (ACS). The
CANDELS/Deep survey covers \sim125 square arcminutes within GOODS-N and
GOODS-S, while the remainder consists of the CANDELS/Wide survey, achieving a
total of \sim800 square arcminutes across GOODS and three additional fields
(EGS, COSMOS, and UDS). We summarize the observational aspects of the survey as
motivated by the scientific goals and present a detailed description of the
data reduction procedures and products from the survey. Our data reduction
methods utilize the most up to date calibration files and image combination
procedures. We have paid special attention to correcting a range of
instrumental effects, including CTE degradation for ACS, removal of electronic
bias-striping present in ACS data after SM4, and persistence effects and other
artifacts in WFC3/IR. For each field, we release mosaics for individual epochs
and eventual mosaics containing data from all epochs combined, to facilitate
photometric variability studies and the deepest possible photometry. A more
detailed overview of the science goals and observational design of the survey
are presented in a companion paper.Comment: 39 pages, 25 figure
CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey
The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS)
is designed to document the first third of galactic evolution, over the
approximate redshift (z) range 8--1.5. It will image >250,000 distant galaxies
using three separate cameras on the Hubble Space Telescope, from the
mid-ultraviolet to the near-infrared, and will find and measure Type Ia
supernovae at z>1.5 to test their accuracy as standardizable candles for
cosmology. Five premier multi-wavelength sky regions are selected, each with
extensive ancillary data. The use of five widely separated fields mitigates
cosmic variance and yields statistically robust and complete samples of
galaxies down to a stellar mass of 10^9 M_\odot to z \approx 2, reaching the
knee of the ultraviolet luminosity function (UVLF) of galaxies to z \approx 8.
The survey covers approximately 800 arcmin^2 and is divided into two parts. The
CANDELS/Deep survey (5\sigma\ point-source limit H=27.7 mag) covers \sim 125
arcmin^2 within GOODS-N and GOODS-S. The CANDELS/Wide survey includes GOODS and
three additional fields (EGS, COSMOS, and UDS) and covers the full area to a
5\sigma\ point-source limit of H \gtrsim 27.0 mag. Together with the Hubble
Ultra Deep Fields, the strategy creates a three-tiered "wedding cake" approach
that has proven efficient for extragalactic surveys. Data from the survey are
nonproprietary and are useful for a wide variety of science investigations. In
this paper, we describe the basic motivations for the survey, the CANDELS team
science goals and the resulting observational requirements, the field selection
and geometry, and the observing design. The Hubble data processing and products
are described in a companion paper.Comment: Submitted to Astrophysical Journal Supplement Series; Revised
version, subsequent to referee repor
- âŠ