Determination of minimal transcriptional signatures of compounds for target prediction

The identification of molecular target and mechanism of action of compounds is a key hurdle in drug discovery. Multiplexed techniques for bead-based expression profiling allow the measurement of transcriptional signatures of compound-treated cells in high-throughput mode. Such profiles can be used to gain insight into compounds' mode of action and the protein targets they are modulating. Through the proxy of target prediction from such gene signatures we explored important aspects of the use of transcriptional profiles to capture biological variability of perturbed cellular assays. We found that signatures derived from expression data and signatures derived from biological interaction networks performed equally well, and we showed that gene signatures can be optimised using a genetic algorithm. Gene signatures of approximately 128 genes seemed to be most generic, capturing a maximum of the perturbation inflicted on cells through compound treatment. Moreover, we found evidence for oxidative phosphorylation to be one of the most general ways to capture compound perturbation

Ultraviolet Imaging of the z=0.23 Cluster Abell 2246

We present deep ultraviolet observations of a field containing the cluster Abell 2246 (z=0.225) which provide far-ultraviolet (FUV) images of some of the faintest galaxies yet observed in that bandpass. Abell 2246 lies within the field of view of Ultraviolet Imaging Telescope (UIT) observations of the quasar HS1700+64, which accumulated over 7100 seconds of UIT FUV exposure time during the Astro-2 mission in March 1995. For objects found on both the FUV and ground-based V-band images, we obtain FUV (l ~ 1520 A) photometry and V-band photometry, as well as mid-UV (l ~ 2490 A) photometry from UIT Astro-1 observations and ground-based I-band photometry. We find five objects in the images which are probably galaxies at the distance of Abell 2246, with FUV magnitudes (m(FUV)) between 18.6 and 19.6, and V magnitudes between 18.4 and 19.6. We find that their absolute FUV fluxes and colors imply strongly that they are luminous galaxies with significant current star formation, as well as some relatively recent, but not current, (> 400 Myr ago) star formation. We interpret the colors of these five objects by comparing them with local objects, redshift-corrected template spectra and stellar population models, finding that they are plausibly matched by 10-Gyr-old population models with decaying star formation, with decay time constants in the range 3 Gyr < t < 5 Gyr, with an additional color component from a single burst of moderate ( ~ 400-500 Myr) age. From derived FUV luminosities we compute current star formation rates. We compare the UV properties of Abell 2246 with those of the Coma cluster, finding that Abell 2246 has significantly more recent star formation, consistent with the Butcher-Oemler phenomenon.Comment: Accepted for publication in the Astronomical Journal, June 1998. 17 Pages AAS latex, includes 4 bitmap .jpg format images and 4 other figures. PDF, Embedded Gzipped PS version (1.9Mb) TeX source and figures available at http://www.astro.virginia.edu/~bd4r/galaxies.htm

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

The Inter-temporal relationship between Risk, Capital and Efficiency: The case of Islamic and conventional banks

The paper investigates the relationship between risk, capital and efficiency for Islamic and conventional banks using a dataset spanning 14 countries over the 2000-2012 period. We use the z-score as a proxy for insolvency risk, cost efficiency is estimated via a stochastic frontier approach and capitalisation is reflected on the equity to assets ratio. An array of bank-specific, macroeconomic and market structure variables are used in a system of three equations, estimated using the seemingly unrelated regression (SUR) technique. We find that the capitalisation response to increases in insolvency risk is more pronounced for Islamic banks but has an approximately five-times smaller effect on risk mitigation compared to conventional banks. Higher cost efficiency is related to lower risk for conventional banks, but the opposite is true for Islamic banks. The link between cost efficiency and capitalisation attests to a substitutional effect for the case of conventional banks, but a complementary effect for Islamic banks. Our findings give new insights on the use of efficiency to gauge capital requirements for financial institutions and are particularly relevant for regulators and policy makers in countries where both bank types operate

The Feasibility of Using Melanopsis

From the 19th International Radiocarbon Conference held in Keble College, Oxford, England, April 3-7, 2006.We investigated the feasibility of using Melanopsis shells as radiocarbon chronometers of paleolakes and springs in the Jordan Valley, Israel. For this purpose, we analyzed the 14C content of aragonite of living Melanopsis shells from different freshwater bodies of the northern Jordan Valley and Lake Kinneret (Sea of Galilee) and compared them to the contemporaneous water values. The Melanopsis shells are in 14C equilibrium with their habitat waters, allowing to specify a particular reservoir age for various water types. We measured ~750 yr for Lake Kinneret, ~2300 yr for northern Jordan, ~4600 yr for springs in the north Kinneret, and ~7200 yr for streams flowing directly from carbonate aquifers. These results were tested and corroborated by analyzing fossil Melanopsis shells of known age, measured on contemporaneous organic matter. We conclude that Melanopsis shells are reliable 14C chronometers and have the potential to be used as paleohydrological tracers.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202