Binary mutual diffusion coefficients measured by the Taylor dispersion method in two different laboratories (University of Naples, Federico II, Italy, and University of Coimbra, Portugal) are ...reported for aqueous solutions of lactose, sucrose, glucose, and fructose at various concentrations (0.001 to 0.1) mol·dm-3 and temperatures (298.15 to 328.15) K. The hydrodynamic radius and activation energy for the diffusion of aqueous sugars are calculated from those results. In addition, the measured diffusion coefficients are used with the Hartley equation to estimate activity coefficients for aqueous lactose, sucrose, glucose, and fructose.
Fragment-based lead generation (FBLG) has recently emerged as an alternative to traditional high throughput screening (HTS) to identify initial chemistry starting points for drug discovery programs. ...In comparison to HTS screening libraries, the screening sets for FBLG tend to contain orders of magnitude fewer compounds, and the compounds themselves are less structurally complex and have lower molecular weight. This report summarises the advent of FBLG within the industry and then describes the FBLG experience at AstraZeneca. We discuss (1) optimising the design of screening libraries, (2) hit detection methodologies, (3) evaluation of hit quality and use of ligand efficiency calculations, and (4) approaches to evolve fragment-based, low complexity hits towards drug-like leads. Furthermore, we exemplify our use of FBLG with case studies in the following drug discovery areas: antibacterial enzyme targets, GPCRs (melanocortin 4 receptor modulators), prostaglandin D2 synthase inhibitors, phosphatase inhibitors (protein tyrosine phosphotase 1B), and protease inhibitors (b-secretase).
Lifetimes of the excited states in the neutron-rich Ti-52,Ti-54 nuclei, produced in a multinucleon-transfer reaction, were measured by employing the Cologne plunger device and the recoil-distance ...Doppler-shift method. The experiment was performed at the Grand Accelerateur National d'Ions Lourds facility by using the Advanced Gamma Tracking Array for the gamma-ray detection, coupled to the large-acceptance variable mode spectrometer for an event-by-event particle identification. A comparison between the transition probabilities obtained from the measured lifetimes of the 2(1)(+) to 8(1)(+) yrast states in Ti-52,Ti-54 and that from the shell-model calculations based on the well-established GXPF1A, GXPF1B, and KB3G fp shell interactions support the N = 32 subshell closure. The B(E2) values for Ti-52 determined in this work are in disagreement with the known data, but are consistent with the predictions of the shell-model calculations and reduce the previously observed pronounced staggering across the even-even titanium isotopes.
A seedling population of Boronia megastigma (Nees) plants was established to explore the extent and degree of variation in plant and chemical characteristics and to select plants of superior ...performance in the production of aromatic concretes for commercial use. Obvious variations between selected individual plants were found in plant habit, growth vigour, flower yield, ease of flower removal for harvesting, concrete yield, β-Ionone and monoterpene content, and the proportion of "volatile" components in the concrete. Selection of elite plants on the basis of so many different criteria is difficult. Quality indices were calculated by incorporating the criteria for each plant into a single value that could be used to rank the plants on plant, chemical, or combined criteria. Ranking using plant and chemical indices gave very different results. Ranking using a quality index that incorporates all criteria offers the opportunity to apply differing weights to individual characteristics. Examples of weighting different criteria are given and the use of weighting is discussed.
We present observations of GRB 060124, the first event for which both the prompt and the afterglow emission could be observed simultaneously and in their entirety by the three Swift instruments. ...Indeed, Swift-BAT triggered on a precursor ~570 s before the main burst peak, and this allowed Swift to repoint the narrow field instruments to the burst position ~350 s before the main burst occurred. GRB 060124 also triggered Konus-Wind, which observed the prompt emission in a harder gamma-ray band (up to 2 MeV). Thanks to these exceptional circumstances, the temporal and spectral properties of the prompt emission can be studied in the optical, X-ray and gamma-ray ranges. While the X-ray emission (0.2–10 keV) clearly tracks the gamma-ray burst, the optical component follows a different pattern, likely indicating a different origin, possibly the onset of external shocks. The prompt GRB spectrum shows significant spectral evolution, with both the peak energy and the spectral index varying. As observed in several long GRBs, significant lags are measured between the hard- and low-energy components, showing that this behaviour extends over 3 decades in energy. The GRB peaks are also much broader at soft energies. This is related to the temporal evolution of the spectrum, and can be accounted for by assuming that the electron spectral index softened with time. The burst energy ($E_{\rm iso} \sim 5$ $\times$ 1053 erg) and average peak energy ($E_{\rm p} \sim 300$ keV) make GRB 060124 consistent with the Amati relation. The X-ray afterglow is characterized by a decay which presents a break at $t_{\rm b} \sim 10^5$ s.
The production of synthetic MHC-peptide tetramers has revolutionized cellular immunology by revealing enormous CD8(+) T cell expansions specific for peptides from various pathogens. A feature of ...these reagents, essential for their staining function, is that they bind T cells with relatively high avidity. This could, theoretically, promote cross-reactivity with irrelevant T cells leading to overestimates of epitope-specific T cell numbers. Therefore, we have investigated the fine specificity of CTL staining with these reagents for comparison with functional data. Using a panel of CTL clones with distinct fine specificity patterns for analogs of an HLA-B8-binding EBV epitope, together with B8 tetramers incorporating these peptides, we show a very good correlation between tetramer staining and peptide activity in cytotoxicity assays. Significant staining only occurred with tetramers that incorporate strong stimulatory agonist peptides and not weak agonists that are unlikely to induce full T cell activation at physiological levels of presentation. In almost every case where a peptide analog had >10-fold less activity than the optimal EBV peptide in cytotoxicity assays, the corresponding tetramer stained with >10-fold less intensity than the EBV epitope tetramer. Furthermore, by examining an EBV-specific clonotypic T cell expansion in EBV-exposed individuals, we show similar fine specificity in tetramer staining of fresh peripheral T cells. Collectively, our data demonstrate the exquisite specificity of class I MHC-peptide tetramers, underlining their accuracy in quantifying only those T cells capable of recognizing the low levels of cell surface peptide presented after endogenous Ag processing.
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to ...support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.
To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).
Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.
Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05 and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.
These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
We present the first images and spectra of an astronomical object, other than the Sun, acquired with a charge coupled device (CCD) imaging X-ray spectrometer. During a 230 s sounding rocket ...observation, we have acquired moderate-resolution spectra and moderate-resolution images of a portion of the Pup A supernova remnant (SNR). Based on these data, we conclude that the X-ray spectrum of Pup A is inconsistent with any single-temperature equilibrium or nonequilibrium plasma model. We find evidence for variations in the emitting plasma on scales as small as 5.0 min and as large as 30.0 min. The spatial structure of the spectral variations in the remnant is found to be inconsistent with the standard Sedov model for the evolution of a SRN into a homogeneous interstellar medium (ISM). We suggest that the remnant is expanding into a region of the ISM having a density of approximately 1 cm(exp -3) with inhomogeneities on the order of 50%. We have found evidence for the presence of a knot of plasma enriched in neon, but require more data to be conclusive.
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