The Water Requirements and Pollutant Potential in the Gasification of Carbonaceous Shales

A laboratory-scale, batch operated gasifier was used to evaluate the heating value, process and cooling water requirements, and water pollution potential of gasification of carbonaceous shales. These potentially valuable fossil fuels are found over large areas of Southern and Eastern Utah and vary widely in quality depending on the amount of intermixed inorganic material. The results indicate that a synthesis gas, consisting primarily of hydrogen and carbon monoxide, can be produced from carbonaceous shales. The total heating values of the synthesis gas from the carbon shales examined ranged from 4 to 62 percent of that of coal. The process water requirements per unit of heaing value obtained for gasification of the carbonaceous shales tended to be 5 to 15 percent higher than that for coal. Cooling water requirements were similarly higher due to the greater quantity of ask quenching water needed for the shales. The quantity of phenols, ammonia-N, and total organic carbon produced from the gasification of coal was significantly greater than for either of the shales, when compared on a mass basis. Differences in process condensate constituents, such as mutagenicity and trace elements, were also determined for the coal and shale samples

High-throughput sequencing: a failure mode analysis

BACKGROUND: Basic manufacturing principles are becoming increasingly important in high-throughput sequencing facilities where there is a constant drive to increase quality, increase efficiency, and decrease operating costs. While high-throughput centres report failure rates typically on the order of 10%, the causes of sporadic sequencing failures are seldom analyzed in detail and have not, in the past, been formally reported. RESULTS: Here we report the results of a failure mode analysis of our production sequencing facility based on detailed evaluation of 9,216 ESTs generated from two cDNA libraries. Two categories of failures are described; process-related failures (failures due to equipment or sample handling) and template-related failures (failures that are revealed by close inspection of electropherograms and are likely due to properties of the template DNA sequence itself). CONCLUSIONS: Preventative action based on a detailed understanding of failure modes is likely to improve the performance of other production sequencing pipelines

Targeting the Heat Shock Protein 90 Dimer with Dimeric Inhibitors

The design, synthesis and biological evaluation of conformationally constrained coumermycin A1 analogues are reported. Compounds were evaluated against both breast cancer (SKBr3 and MCF7) and prostate cancer (PC3mm2, A549 and HT29) cell lines. Non-noviosylated coumermycin A1 analogues that manifest potent anti-proliferative activity resulting from Hsp90 inhibition are provided, wherein replacement of the stereochemically complex noviose sugar with readily available piperidine rings resulted in ~100 fold increase in anti-proliferative activities as compared to coumermycin A1, producing small molecule Hsp90 inhibitors that exhibit nanomolar activities

Predictive value of midtrimester universal cervical length screening based on parity

OBJECTIVES: To evaluate the effect of parity on performance characteristics of midtrimester cervical length (CL) in predicting spontaneous preterm birth (sPTB) before 37 weeks. METHODS: This was a retrospective cohort study of 13,508 women with no history of sPTB undergoing universal transvaginal CL screening at 17 to 23 weeks\u27 gestation from 2011 to 2016. Patients who declined screening or with unknown delivery outcomes were excluded. Areas under the receiver operator characteristic curves were used to assess and compare the predictive ability of CL screening for sPTB. The sensitivity, specificity, and positive and negative predictive values were estimated for specific CL cutoffs for prediction of sPTB. RESULTS: There were 20,100 patients, of whom 2087 (10%) declined screening and 4505 (22%) did not meet inclusion criteria. Of the remaining 13,508 patients, 43% were nulliparous. The incidence rates of sPTB were 6.5% in nulliparas and 4.9% in multiparas (P \u3c .001). The mean CLs were 39.9 mm in nulliparas and 41.8 mm in multiparas (P \u3c .001), and those of the first percentiles were 19.0 mm in nulliparas and 24.0 mm in multiparas. Cervical length was significantly more predictive of sPTB in nulliparas (area under the curve, 0.67; 95% confidence interval, 0.63-0.70; versus 0.61, 95% confidence interval, 0.57-0.63; P = .008). At CL cutoffs of 10, 15, 20, and 25 mm or less, the sensitivity was lower in multiparas, and the specificity was comparable between the groups. CONCLUSIONS: Midtrimester CL is less predictive of sPTB in multiparas compared to nulliparas. The poor predictive ability, especially in multiparas, calls into question the value of universal CL screening in this population

Synthesis and Biological Evaluation of Coumarin Replacements of Novobiocin as Hsp90 Inhibitors

Since Hsp90 modulates all six hallmarks of cancer simultaneously, it has become an attractive target for the development of cancer chemotherapeutics. In an effort to develop more efficacious compounds for Hsp90 inhibition, novobiocin analogues were prepared by replacing the central coumarin core with naphthalene, quinolinone, and quinoline surrogates. These modifications allowed for modification of the 2-position, which was previously unexplored. Biological evaluation of these compounds suggests a hydrophobic pocket about the 2-position of novobiocin. Anti-proliferative activities of these analogues against multiple cancer cell lines identified 2-alkoxyquinoline derivatives to exhibit improved activity

Characterization of a novel novobiocin analogue as a putative Cterminal inhibitor of heat shock protein 90 in prostate cancer cells

PURPOSE: Hsp90 is important in the folding, maturation and stabilization of pro-tumorigenic client proteins and represents a viable drug target for the design of chemotherapies. Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client protein expression. We now report the characterization of the novel novobiocin analogue, F-4, which demonstrates improved cytotoxicity in prostate cancer cell lines compared to the N-terminal inhibitor, 17-AAG. MATERIALS AND METHODS: LNCaP and PC-3 cells were treated with 17-AAG or F-4 in anti-proliferative, apoptosis, cell cycle and cytotoxicity assays. Western blot and prostate specific antigen (PSA) ELISAs were used to determine client protein degradation, induction of Hsp90 and to assess the functional status of the androgen receptor (AR) in response to F-4 treatment. Surface Plasmon Resonance (SPR) was also used to determine the binding properties of F-4 to Hsp90. RESULTS: F-4 demonstrated improved potency and efficacy compared to novobiocin in anti-proliferative assays and decreased expression of client proteins. PSA secretion was inhibited in a dose-dependent manner that paralleled a decrease in AR expression. The binding of F-4 to Hsp90 was determined to be saturable with a binding affinity (Kd) of 100 µM. In addition, superior efficacy was demonstrated by F-4 compared to 17-AAG in experiments measuring cytotoxicity and apoptosis. CONCLUSIONS: These data reveal distinct modes of action for N-terminal and C-terminal Hsp90 inhibitors, which may offer unique therapeutic benefits for the treatment of prostate cancer

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

BackgroundThe majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).Methods/DesignThe HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense&reg;). The pharmacies have been randomised to either \u27Pharmacist Care Group\u27 (PCG) or \u27Usual Care Group\u27 (UCG). To check for \u27Hawthorne effect\u27 in the UCG, a third group of patients \u27Hidden Control Group\u27 (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.DiscussionTo our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the \u27Hawthorne effect\u27 in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12609000705280<br /